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Human cleavage-stage embryos frequently acquire chromosomal aneuploidies during mitosis due to unknown mechanisms. Here, we show that S phase at the 1-cell stage shows replication fork stalling, low fork speed, and DNA synthesis extending into G2 phase. DNA damage foci consistent with collapsed replication forks, DSBs, and incomplete replication form in G2 in an ATR- and MRE11-dependent manner, followed by spontaneous chromosome breakage and segmental aneuploidies. Entry into mitosis with incomplete replication results in chromosome breakage, whole and segmental chromosome errors, micronucleation, chromosome fragmentation, and poor embryo quality. Sites of spontaneous chromosome breakage are concordant with sites of DNA synthesis in G2 phase, locating to gene-poor regions with long neural genes, which are transcriptionally silent at this stage of development. Thus, DNA replication stress in mammalian preimplantation embryos predisposes gene-poor regions to fragility, and in particular in the human embryo, to the formation of aneuploidies, impairing developmental potential.
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Rotura Cromosómica , Segregación Cromosómica , Aneuploidia , Animales , ADN , Replicación del ADN , Desarrollo Embrionario/genética , Humanos , Mamíferos/genéticaRESUMEN
We report 4 highly pathogenic avian influenza A(H5N1) clade 2.3.4.4.b viruses in samples collected during June 2023 from Royal terns and Cabot's terns in Brazil. Phylodynamic analysis revealed viral movement from Peru to Brazil, indicating a concerning spread of this clade along the Atlantic Americas migratory bird flyway.
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Charadriiformes , Subtipo H5N1 del Virus de la Influenza A , Gripe Aviar , Gripe Humana , Animales , Humanos , Gripe Aviar/epidemiología , Animales Salvajes , Brasil/epidemiología , Aves , FilogeniaRESUMEN
The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2/genética , Vacunación , Inmunización Secundaria , Anticuerpos Neutralizantes , Epítopos/genética , Vacunas CombinadasRESUMEN
INTRODUCTION: Frailty is a syndrome depicting vulnerability of multiple physiological systems to stressors. Frailty measures, such as Hospital Frailty Risk Score (HFRS), can be used to identify frailty and predict outcome more reliably. Our aim was to analyse a blood-based frailty index (FI-B) at admission for prediction outcome of patients with acute ischemic stroke (AIS) undergoing endovascular treatment (EVT). METHODS: We conducted a retrospective study of consecutive AIS patients undergoing EVT in a single tertiary centre during a period of five years. A set of eighteen blood parameters at admission were collected and nine of these were utilized to calculate FI-B. We analysed the relationship between FI-B and HFRS. We examined the baseline characteristics of the study population based on FI-B-tertiles. Multivariable regression models were employed to ascertain the association between FI-B and in-hospital mortality, 3-month mortality and 3-month functional outcome. RESULTS: The final study population comprised 489 patients, with a median age of 75.6 years, 49.5% of patients were male. The FI-B exhibited a weak positive correlation with HFRS (rho=0.113, p=0.016). Patients in higher FI-B-tertiles were older and more frequently presented with pre-stroke functional dependence and comorbidities. Moreover, an increasing FI-B was independently associated with increased likelihood of in-hospital mortality (adjusted odds ratio [aOR]=1.29, 95% confidence interval [95%CI]=1.14-1.47), 3-month mortality (aOR=1.26, 95%CI=1.11-1.43), and of increasing 3-month functional disability measured by utility-weighted modified Rankin Scale (common aOR=0.84, 95%CI=0.76-0.93). CONCLUSION: A frailty index based on blood values at admission was able to identify frailty in AIS patients undergoing EVT and was an independent predictor of short- and medium-term outcome after stroke.
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Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 virus was detected in the South American sea lions found dead in Santa Catarina, Brazil, in October 2023. Whole genome sequencing and comparative phylogenetic analysis were conducted to investigate the origin, genetic diversity, and zoonotic potentials of the H5N1 viruses. The H5N1 viruses belonged to the genotype B3.2 of clade 2.3.4.4b H5N1 virus, which was identified in North America and disseminated to South America. They have acquired new amino acid substitutions related to mammalian host affinity. Our study provides insights into the genetic landscape of HPAI H5N1 viruses in Brazil, highlighting the continuous evolutionary processes contributing to their possible adaptation to mammalian hosts.
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Subtipo H5N1 del Virus de la Influenza A , Filogenia , Leones Marinos , Secuenciación Completa del Genoma , Animales , Leones Marinos/virología , Brasil , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/clasificación , Infecciones por Orthomyxoviridae/veterinaria , Infecciones por Orthomyxoviridae/virología , Genoma Viral , Genotipo , Variación GenéticaRESUMEN
INTRODUCTION: The Boston criteria v2.0 for cerebral amyloid angiopathy (CAA) incorporated non-hemorrhagic imaging markers. Their prevalence and significance in patients with cognitive impairment remain uncertain. METHODS: We studied 622 memory clinic patients with available magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers. Two raters assessed non-hemorrhagic markers, and we explored their association with clinical characteristics through multivariate analyses. RESULTS: Most patients had mild cognitive impairment; median age was 71 years and 50% were female. Using the v2.0 criteria, possible or probable CAA increased from 75 to 383 patients. Sixty-eight percent of the sample had non-hemorrhagic CAA markers, which were independently associated with age (odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.01-1.07), female sex (OR = 1.68, 95% CI = 1.11-2.54), and hemorrhagic CAA markers (OR = 2.11, 95% CI = 1.02-4.35). DISCUSSION: Two-thirds of patients from a memory clinic cohort had non-hemorrhagic CAA markers, increasing the number of patients meeting the v2.0 CAA criteria. Longitudinal approaches should explore the implications of these markers, particularly the hemorrhagic risk in this population. HIGHLIGHTS: The updated Boston criteria for cerebral amyloid angiopathy (CAA) now include non-hemorrhagic markers. The prevalence of non-hemorrhagic CAA markers in memory clinic patients is unknown. Two-thirds of patients in our memory clinic presented non-hemorrhagic CAA markers. The presence of these markers was associated with age, female sex, and hemorrhagic CAA markers. The hemorrhagic risk of patients presenting these type of markers remains unclear.
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Biomarcadores , Angiopatía Amiloide Cerebral , Disfunción Cognitiva , Imagen por Resonancia Magnética , Humanos , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/complicaciones , Femenino , Masculino , Anciano , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Persona de Mediana Edad , Péptidos beta-Amiloides/líquido cefalorraquídeo , Trastornos de la Memoria/etiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Little is currently known about vaccine effectiveness (VE) for either 2 doses of Oxford-AstraZeneca (ChAdOx1) viral vector vaccine or CoronaVac (Instituto Butantan) inactivated viral vaccine followed by a third dose of mRNA vaccine (Pfizer/BioNTech) among healthcare workers (HCWs). METHODS: We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil from January to December 2021. VE was defined as 1 - incidence rate ratio (IRR), with IRR determined using Poisson models with the occurrence of laboratory-confirmed coronavirus disease 2019 (COVID-19) infection as the outcome, adjusting for age, sex, and job type. We compared those receiving viral vector or inactivated viral primary series (2 doses) with those who received an mRNA booster. RESULTS: A total of 11 427 HCWs met the inclusion criteria. COVID-19 was confirmed in 31.5% of HCWs receiving 2 doses of CoronaVac vaccine versus 0.9% of HCWs receiving 2 doses of CoronaVac vaccine with mRNA booster (P < .001) and 9.8% of HCWs receiving 2 doses of ChAdOx1 vaccine versus 1% among HCWs receiving 2 doses of ChAdOx1 vaccine with mRNA booster (P < .001). In the adjusted analyses, the estimated VE was 92.0% for 2 CoronaVac vaccines plus mRNA booster and 60.2% for 2 ChAdOx1 vaccines plus mRNA booster, when compared with those with no mRNA booster. Of 246 samples screened for mutations, 191 (77.6%) were Delta variants. CONCLUSIONS: While 2 doses of ChAdOx1 or CoronaVac vaccines prevent COVID-19, the addition of a Pfizer/BioNTech booster provided significantly more protection.
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COVID-19 , Vacunas Virales , Humanos , Adolescente , Adulto , Brasil/epidemiología , Estudios Retrospectivos , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Personal de Salud , ARN MensajeroRESUMEN
BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
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COVID-19 , Fibrosis Pulmonar , Síndrome de Dificultad Respiratoria , Humanos , Femenino , Fibrosis Pulmonar/metabolismo , COVID-19/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Pulmón/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Síndrome de Dificultad Respiratoria/metabolismoRESUMEN
BACKGROUND: Since its beginning, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been a challenge for clinical and molecular diagnostics, because it has been caused by a novel viral agent. Whole-genome sequencing assisted in the characterization and classification of SARS-CoV-2, and it is an essential tool to genomic surveillance aiming to identify potentials hot spots that could impact on vaccine immune response and on virus diagnosis. We describe two cases of failure at the N2 target of the RT-PCR test Xpert® Xpress SARS-CoV-2. METHODS: Total nucleic acid from the Nasopharyngeal (NP) and oropharyngeal (OP) swab samples and cell supernatant isolates were obtained. RNA samples were submitted to random amplification. Raw sequencing data were subjected to sequence quality controls, removal of human contaminants by aligning against the HG19 reference genome, taxonomic identification of other pathogens and genome recovery through assembly and manual curation. RT-PCR test Xpert® Xpress SARS-CoV-2 was used for molecular diagnosis of SARS-CoV-2 infection, samples were tested in duplicates. RESULTS: We identified 27 samples positive for SARS-CoV-2 with a nucleocapsid (N) gene drop out on Cepheid Xpert® Xpress SARS-CoV-2 assay. Sequencing of 2 of 27 samples revealed a single common mutation in the N gene C29197T, potentially involved in the failed detection of N target. CONCLUSIONS: This study highlights the importance of genomic data to update molecular tests and vaccines.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sensibilidad y Especificidad , Nucleocápside/genética , Mutación , Prueba de COVID-19RESUMEN
The general assumption that the survival patterns of tropical and southern temperate birds are similar lacks empirical data from higher latitudes. Regional comparisons of New World species are rare, and this assumption has been based on data from African studies. Here, we estimate the survival rates of 88 tropical and southern temperate bird populations (69 species) from eight localities in South America to evaluate the hypothesis that the survival of these populations is homogeneous at the regional scale. We estimated survival based on the Cormack-Jolly-Seber model and compared values from different environments. The survival estimates ranged from 0.30 to 0.80 (0.56 ± 0.12). Apparent survival did not differ significantly between low-latitude tropical environments (03°S) and the other sites from high-latitudes (between 22° and 34°S). Despite a predicted positive trend, body size was not significantly related to survival among passerines. On the other hand, phylogenetic relationships explained more than a third of the variation in bird survival. Based on the largest available database on South American bird species, our findings support the hypothesis that bird survival is homogeneous, at the regional scale, along the southern hemisphere. In particular, we reinforce the hypothesis that climatic variation has a limited influence on bird survival in the southern hemisphere.
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Clima Tropical , Filogenia , América del Sur , Tamaño CorporalRESUMEN
BACKGROUND AND PURPOSE: A primary admission of patients with suspected acute ischemic stroke and large vessel occlusion (LVO) to centers capable of providing endovascular stroke therapy (EVT) may induce shorter time to treatment and better functional outcomes. One of the limitations in this strategy is the need for accurately identifying LVO patients in the prehospital setting. We aimed to study the feasibility and diagnostic performance of point-of-care ultrasound (POCUS) for the detection of LVO in patients with acute stroke. METHODS: We conducted a proof-of-concept study and selected 15 acute ischemic stroke patients with angiographically confirmed LVO and 15 patients without LVO. Duplex ultrasonography (DUS) of the common carotid arteries was performed, and flow profiles compatible with LVO were scored independently by one experienced and one junior neurologist. RESULTS: Among the 15 patients with LVO, 6 patients presented with an occlusion of the carotid-T and 9 patients presented with an M1 occlusion. Interobserver agreement between the junior and the experienced neurologist was excellent (kappa = 0.813, p < 0.001). Flow profiles of the CAA allowed the detection of LVO with a sensitivity of 73%, a positive predictive value of 92 and 100%, and a c-statistics of 0.83 (95%CI = 0.65-0.94) and 0.87 (95%CI = 0.69-0.94) (experienced neurologist and junior neurologist, respectively). In comparison with clinical stroke scales, DUS was associated with better trade-off between sensitivity and specificity. CONCLUSION: POCUS in acute stroke setting is feasible, it may serve as a complementary tool for the detection of LVO and is potentially applicable in the prehospital phase.
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Isquemia Encefálica , Servicios Médicos de Urgencia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Sistemas de Atención de Punto , Accidente Cerebrovascular/diagnóstico , Sensibilidad y Especificidad , Ultrasonografía , Isquemia Encefálica/terapia , Estudios RetrospectivosRESUMEN
To review the use of epidural electric stimulation test, pressure waveform analysis, and ultrasound assessment of injection as bedside methods for confirming identification of the epidural space in adults with acute pain, the PubMed database was searched for relevant reports between May and August 2022. Studies reporting diagnostic accuracy with conventional Touhy needles and epidural catheters were further selected for meta-analysis. Sensitivity and specificity were estimated using univariate logistic regression for electric stimulation and pressure analysis, and pooling of similar studies for ultrasound. Risk of bias and applicability was assessed using QUADAS-2. For electric stimulation, pressure waveform analysis, and ultrasound, respectively 35, 22, and 28 reports were included in the review and 9, 9, and 7 studies in the meta-analysis. Electric stimulation requires wire-reinforced catheters and an adequate nerve stimulator, does not reliably identify intravascular placement, and is affected by local anaesthetics. Sensitivity was 95% (95% CI 93-96%, N = 550) and specificity unknown (95% CI 33-94%, N = 44). Pressure waveform analysis is unaffected by local anaesthetics, but does not identify intravascular nor intrathecal catheters. Sensitivity was 90% (95% CI 72-97%, N = 694) and specificity 88% (95% CI 78-94%, N = 67). B-mode, M-mode and doppler ultrasound may be challenging, and data is still limited. Risk of bias was significant and accuracy estimates must be interpreted with caution. Electric stimulation and pressure waveform analysis seem clinically useful, although they must be interpreted cautiously. In the future, clinical trials in patients with difficult anatomy will likely be most useful. Ultrasound requires further investigation.
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Dolor Agudo , Anestesia Epidural , Adulto , Humanos , Espacio Epidural/diagnóstico por imagen , Anestésicos Locales , Dolor Agudo/diagnóstico , Anestesia Epidural/métodos , Estimulación EléctricaRESUMEN
OBJECTIVES: To evaluate the value of an extended emergency computed tomography angiography (CTA) including cardiac imaging in patients with acute ischemic stroke for the detection of left atrial appendage (LAA) thrombus compared to transesophageal echocardiography (TEE) as a reference standard. MATERIALS AND METHODS: We conducted a retrospective case-control study of patients with presumed acute ischemic stroke who had undergone non-ECG-gated CTA for the craniocervical vessels with an extended coverage including the heart in the context of emergency stroke evaluation and for whom TEE was available as part of the routine stroke diagnostic. We selected cases with evidence of LAA thrombus in TEE and controls without LAA thrombus in TEE in a 1:3 ratio. Two independent observers analyzed CTA images for presence of LAA thrombus and were blinded to the presence of thrombus in TEE. RESULTS: Twenty-two patients with LAA thrombus in TEE, and 66 patients without LAA thrombus in TEE were included. The detection of LAA thrombus using CTA showed a sensitivity of 63.6%, a specificity of 81.8%, a positive predictive value of 53.9% and a negative predicted value of 87.1%. Interobserver agreement was only moderate (Cohen´s κ = 0.43). CONCLUSIONS: An extended emergency CTA including cardiac imaging can be helpful in early risk stratification in patients with stroke of cardioembolic origin. However, our data show that a standard CTA of craniocervical vessels with extended coverage of the heart is of limited value when compared to TEE, the standard method of detecting LAA thrombi.
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Apéndice Atrial , Fibrilación Atrial , Cardiopatías , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Angiografía por Tomografía Computarizada , Ecocardiografía Transesofágica/métodos , Apéndice Atrial/diagnóstico por imagen , Estudios Retrospectivos , Estudios de Casos y Controles , Cardiopatías/diagnóstico , Trombosis/complicaciones , Trombosis/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
OBJECTIVE: Understanding the lateralization factors, including the anatomic and hemodynamic mechanisms, is essential for diagnosing cardio-embolic stroke. This study aims to investigate the elements, for the first time together, that could affect the laterality of stroke. METHODS: We performed a monocentric retrospective case-control study based on prospective registries of acute ischemic stroke patients in the comprehensive stroke center of the RWTH University hospital of Aachen for three years (June 2018-June 2021). We enrolled 222 patients with cardioembolic stroke (136 left stroke and 86 right stroke) admitted for first-ever acute ischemic stroke with unilateral large vessel occlusion of the anterior circulation. The peak systolic velocity (PSV) asymmetry of middle cerebral artery (MCA) was assessed by doppler as well as internal carotid artery (ICA) angle, aortic arch (AA) branching pattern and anatomy were assessed by CT-Angiography. RESULTS: We found that the increasing left ICA angle (p = 0.047), presence of bovine type AA anatomy (p = 0.041) as well as slow PSV of the right MCA with a value of >15% than left (p = 0.005) were the predictors for left stroke lateralization, while the latter was an independent predictor for the left stroke (OR=3.341 [1.415-7.887]). Inter-Rater Reliability ranged from moderate to perfect agreement. CONCLUSION: The predictors for left stroke lateralization include the higher values of left ICA angle, presence of the bovine type AA and the slow right MCA PSV.
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Enfermedades de las Arterias Carótidas , Accidente Cerebrovascular Embólico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Animales , Bovinos , Estudios Retrospectivos , Estudios Prospectivos , Estudios de Casos y Controles , Reproducibilidad de los Resultados , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Arteria Carótida Interna/diagnóstico por imagenRESUMEN
A 68-year-old Brazilian woman had 3 months of progressive fatigue, difficulty walking and 18 kg weight loss. On examination, there was gait apraxia and executive dysfunction. MR scan of brain showed communicating hydrocephalus and a cerebrospinal fluid showed 105 white cells/µL (≤5), predominantly lymphocytes, protein of 1.35 g/L (0.15-0.45) and the glucose content of 0.06 mmol/L (3.3-4.4). We suspected an infective cause and used of metagenomic next-generation sequencing to diagnose neurocysticercosis. This case highlights the challenge of diagnosing chronic meningitis and the relevance of genetic approaches in diagnosing neurological infections.
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Hidrocefalia , Meningitis , Neurocisticercosis , Femenino , Humanos , Anciano , Neurocisticercosis/diagnóstico , Neurocisticercosis/genética , Encéfalo/diagnóstico por imagen , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND AND PURPOSE: It is currently thought that embolic stroke of undetermined source (ESUS) has diverse underlying hidden etiologies, of which cardioembolism is one of the most important. The subgroup of patients with this etiology could theoretically benefit from oral anticoagulation, but it remains unclear if these patients can be correctly identified from other ESUS subgroups and which markers should be used. We aimed to determine whether a machine-learning (ML) model could discriminate between ESUS patients with cardioembolic and those with non-cardioembolic profiles using baseline demographic and laboratory variables. METHODS: Based on a prospective registry of consecutive ischemic stroke patients submitted to acute revascularization therapies, an ML model was trained using the age, sex and 11 selected baseline laboratory parameters of patients with known stroke etiology, with the aim of correctly identifying patients with cardioembolic and non-cardioembolic etiologies. The resulting model was used to classify ESUS patients into those with cardioembolic and those with non-cardioembolic profiles. RESULTS: The ML model was able to distinguish patients with known stroke etiology into cardioembolic or non-cardioembolic profile groups with excellent accuracy (area under the curve = 0.82). When applied to ESUS patients, the model classified 40.3% as having cardioembolic profiles. ESUS patients with cardioembolic profiles were older, more frequently female, more frequently had hypertension, less frequently were active smokers, had higher CHA2 DS2 -VASc (Congestive heart failure or left ventricular systolic dysfunction, Hypertension, Age ≥ 75 [doubled], Diabetes, Stroke/transient ischemic attack [doubled], Vascular disease, Age 65-74, and Sex category) scores, and had more premature atrial complexes per hour. CONCLUSIONS: An ML model based on baseline demographic and laboratory variables was able to classify ESUS patients into cardioembolic or non-cardioembolic profile groups and predicted that 40% of the ESUS patients had a cardioembolic profile.
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Accidente Cerebrovascular Embólico , Hipertensión , Embolia Intracraneal , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Anciano , Accidente Cerebrovascular Embólico/etiología , Femenino , Humanos , Hipertensión/complicaciones , Embolia Intracraneal/complicaciones , Ataque Isquémico Transitorio/complicaciones , Factores de Riesgo , Accidente Cerebrovascular/complicacionesRESUMEN
The ability of the new coronavirus SARS-CoV-2 to spread and contaminate is one of the determinants of the COVID-19 pandemic status. SARS-CoV-2 has been detected in saliva consistently, with similar sensitivity to that observed in nasopharyngeal swabs. We conducted ultrasound-guided postmortem biopsies in COVID-19 fatal cases. Samples of salivary glands (SGs; parotid, submandibular, and minor) were obtained. We analyzed samples using RT-qPCR, immunohistochemistry, electron microscopy, and histopathological analysis to identify SARS-CoV-2 and elucidate qualitative and quantitative viral profiles in salivary glands. The study included 13 female and 11 male patients, with a mean age of 53.12 years (range 8-83 years). RT-qPCR for SARS-CoV-2 was positive in 30 SG samples from 18 patients (60% of total SG samples and 75% of all cases). Ultrastructural analyses showed spherical 70-100 nm viral particles, consistent in size and shape with the Coronaviridae family, in the ductal lining cell cytoplasm, acinar cells, and ductal lumen of SGs. There was also degeneration of organelles in infected cells and the presence of a cluster of nucleocapsids, which suggests viral replication in SG cells. Qualitative histopathological analysis showed morphologic alterations in the duct lining epithelium characterized by cytoplasmic and nuclear vacuolization, as well as nuclear pleomorphism. Acinar cells showed degenerative changes of the zymogen granules and enlarged nuclei. Ductal epithelium and serous acinar cells showed intense expression of ACE2 and TMPRSS receptors. An anti-SARS-CoV-2 antibody was positive in 8 (53%) of the 15 tested cases in duct lining epithelial cells and acinar cells of major SGs. Only two minor salivary glands were positive for SARS-CoV-2 by immunohistochemistry. Salivary glands are a reservoir for SARS-CoV-2 and provide a pathophysiological background for studies that indicate the use of saliva as a diagnostic method for COVID-19 and highlight this biological fluid's role in spreading the disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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COVID-19/virología , SARS-CoV-2/patogenicidad , Saliva/virología , Glándulas Salivales/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Reino Unido , Adulto JovenRESUMEN
Migratory birds are implicated in dispersing haemosporidian parasites over great geographic distances. However, their role in sharing these vector-transmitted blood parasites with resident avian host species along their migration flyway is not well understood. We studied avian haemosporidian parasites in 10 localities where Chilean Elaenia, a long-distance Neotropical austral migrant species, spends part of its annual cycle to determine local parasite transmission among resident sympatric host species in the elaenia's distributional range across South America. We sampled 371 Chilean Elaenias and 1,818 birds representing 243 additional sympatric species from Brazilian wintering grounds to Argentinian breeding grounds. The 23 haemosporidian lineages found in Chilean Elaenias exhibited considerable variation in distribution, specialization, and turnover across the 10 avian communities in South America. Parasite lineage dissimilarity increased with geographic distance, and infection probability by Parahaemoproteus decreased in localities harbouring a more diverse haemosporidian fauna. Furthermore, blood smears from migrating Chilean Elaenias and local resident avian host species did not contain infective stages of Leucocytozoon, suggesting that transmission did not take place in the Brazilian stopover site. Our analyses confirm that this Neotropical austral migrant connects avian host communities and transports haemosporidian parasites along its distributional range in South America. However, the lack of transmissive stages at stopover site and the infrequent parasite lineage sharing between migratory host populations and residents at breeding and wintering grounds suggest that Chilean Elaenias do not play a significant role in dispersing haemosporidian parasites, nor do they influence local transmission across South America.
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Enfermedades de las Aves , Haemosporida , Parásitos , Passeriformes , Plasmodium , Animales , Prevalencia , Chile/epidemiología , Enfermedades de las Aves/epidemiología , Enfermedades de las Aves/parasitología , Haemosporida/genética , FilogeniaRESUMEN
PURPOSE: Clinical outcome of stroke patients is usually classified into favorable (modified Rankin scale (mRS) 0-2) and unfavorable (mRS 3-5) outcome according to the modified Rankin scale. We took a closer look at the clinical course of thrombectomy stroke patients with formal unfavorable outcome and assessed whether we could achieve our treatment goals and/or neurological improvement in these patients. METHODS: We studied 107 patients with occlusions in the terminal carotid artery or the M1 segment of the middle cerebral artery, in whom complete recanalization (eTICI 3) could be achieved, and who had an mRS of 3-5 at 90 days. We analyzed whether an individual treatment goal (i.e., preventing aphasia) and neurological improvement (NIHSS) could be achieved. In addition, we examined whether there was clinical improvement on the mRS. RESULTS: The treatment goal was achieved in 52% (53/103) and neurological improvement in 65% (67/103). mRS 90 days post-stroke was better than mRS upon admission in 36% (38/107) and better than or equal to mRS upon admission in 80% (86/107). Of the 93 patients with known pre-stroke mRS, 18% (17/93) already had an mRS ≥ 3, with 15 of these 17 patients having a worse mRS on admission than before. Of these 17 patients, 18% regained baseline, and 24% improved from admission. CONCLUSION: Dichotomizing the mRS into favorable and unfavorable outcome does not do justice to the full spectrum of stroke. Patients with formal unfavorable outcome after mRS can improve neurologically, achieve treatment goals, and even regain their admission or pre-stroke mRS.
Asunto(s)
Accidente Cerebrovascular , Trombectomía , Humanos , Arteria Cerebral Media , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION: Ischemic stroke is a potential complication of hypereosinophilic syndromes (HES), and little is known about underlying pathophysiological mechanisms. We aimed to describe the imaging patterns of cerebral ischemia in patients with HES. METHODS: An individual case is reported. A systematic PubMed review of all records reporting adult patients with HES who suffered ischemic stroke and for whom neuroimaging details of ischemic lesions were available was performed. RESULTS: A 60-year-old man presented with progressive subacute gait difficulty and psychomotor slowing as well as an absolute eosinophilia (2.2 × 109/L) at admission. Brain magnetic resonance tomography revealed multiple acute and subacute internal and external border zone infarcts. Cardiac diagnostic suggested the presence of endomyocarditis. After extensive diagnostic workup, idiopathic HES was diagnosed. The systematic review yielded 183 studies, of which 40 fulfilled the inclusion criteria: a total of 64 patients (31.3% female), with mean age 51.1 years and a median absolute eosinophile count at diagnosis of 10.2 × 109/L were included in the analyses. A border zone pattern of cerebral ischemic lesions was reported in 41 patients (64.1%). Isolated peripheral infarcts were reported in 7 patients (10.9%). Sixteen patients had multiple acute infarcts with no border zone distribution (25.0%). An intracardiac thrombus was reported in 15/60 patients (25%), and findings suggestive of endomyocarditis or endomyocardial fibrosis were found in 31/60 patients (51.7%). CONCLUSIONS: Border zone distribution of cerebral ischemia without hemodynamic compromise is the most frequent imaging pattern in patients with HES, occurring in 2/3 of patients who develop ischemic stroke.