Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Purpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

Perception of near-threshold visual stimuli is influenced by prestimulus alpha-band amplitude but not by alpha phase.

Ongoing brain activity preceding visual stimulation has been suggested to shape conscious perception. According to the pulsed inhibition framework, bouts of functional inhibition arise in each alpha cycle (every ~100 ms), allowing information to be processed in a pulsatile manner. Consequently, it has been hypothesized that perceptual outcome can be influenced by the specific phase of alpha oscillations prior to the stimulus onset, although empirical findings are controversial. In this study, we aimed to shed light on the role of prestimulus alpha oscillations in visual perception. To this end, we recorded electroencephalographic activity, while participants performed three near-threshold visual detection tasks with different attentional involvement: a no-cue task, a noninformative cue task (50% validity), and an informative cue task (100% validity). Cluster-based permutation statistics were complemented with Bayesian analyses to test the effect of prestimulus oscillatory amplitude and phase on visual awareness. We additionally examined whether these effects differed in trials with low and high oscillatory amplitude, as expected from the pulsed inhibition theory. Our results show a clear effect of prestimulus alpha amplitude on conscious perception, but only when alpha fluctuated spontaneously. In contrast, we did not find any evidence that prestimulus alpha phase influenced perceptual outcome, not even when differentiating between low- and high-amplitude trials. Furthermore, Bayesian analysis provided moderate evidence in favor of the absence of phase effects. Taken together, our results challenge the central theoretical predictions of the pulsed inhibition framework, at least for the particular experimental conditions used here.

The effectiveness of a school mindfulness-based intervention on the neural correlates of inhibitory control in children at risk: A randomized control trial.

Interest in the applications of mindfulness practice in education is growing in the scientific community. Recent research has shown that mindfulness practice in schools may be beneficial for executive functions (EFs) which are abilities crucial for healthy development. The study of the effects of mindfulness practices on children's neural correlates of EFs, particularly inhibitory control, may provide relevant information about the impact and mechanisms of mindfulness-based interventions (MBIs) in children. The aim of the present study was to investigate the effects of a MBI in elementary school children on the neural correlates of inhibitory control via a randomized controlled trial. Children from two 4th grade classrooms and two 5th grade classrooms located in a school identified as having low socioeconomic status in Santiago de Chile were randomly assigned to either receive a MBI or serve as active controls and receive a social skills program. Both before and after the interventions, electroencephalographic activity was recorded during a modified version of the Go/Nogo task in a subsample of children in each group. Additionally, teachers completed questionnaires of students' EFs and students completed self-report measures. Results revealed increases in EFs assessed by questionnaires together with improved P3 amplitude associated with successful response inhibition in children who received the MBI compared to active controls. These results contribute to the understanding of the ways in which mindfulness practices can promote the development of inhibitory control together with EF improvement, factors identified as critical for children's social and emotional development and positive mental health. RESEARCH HIGHLIGHTS: This study investigated the effects of a mindfulness-based intervention in children from a low socioeconomic status school on neural correlates of EFs. Children performed a Go/Nogo task while electroencephalographic activity was recorded and completed questionnaires before and after a MBI or an active control program. Improvements in EFs assessed by questionnaires together with an increased Nogo-P3 activity associated with successful inhibition in children who received the MBI were found. The results could contribute to understand how mindfulness practice can promote the development of inhibitory control in children from vulnerable populations.

The natural frequencies of the resting human brain: An MEG-based atlas.

Brain oscillations are considered to play a pivotal role in neural communication. However, detailed information regarding the typical oscillatory patterns of individual brain regions is surprisingly scarce. In this study we applied a multivariate data-driven approach to create an atlas of the natural frequencies of the resting human brain on a voxel-by-voxel basis. We analysed resting-state magnetoencephalography (MEG) data from 128 healthy adult volunteers obtained from the Open MEG Archive (OMEGA). Spectral power was computed in source space in 500 ms steps for 82 frequency bins logarithmically spaced from 1.7 to 99.5 Hz. We then applied k-means clustering to detect characteristic spectral profiles and to eventually identify the natural frequency of each voxel. Our results provided empirical confirmation of the canonical frequency bands and revealed a region-specific organisation of intrinsic oscillatory activity, following both a medial-to-lateral and a posterior-to-anterior gradient of increasing frequency. In particular, medial fronto-temporal regions were characterised by slow rhythms (delta/theta). Posterior regions presented natural frequencies in the alpha band, although with differentiated generators in the precuneus and in sensory-specific cortices (i.e., visual and auditory). Somatomotor regions were distinguished by the mu rhythm, while the lateral prefrontal cortex was characterised by oscillations in the high beta range (>20 Hz). Importantly, the brain map of natural frequencies was highly replicable in two independent subsamples of individuals. To the best of our knowledge, this is the most comprehensive atlas of ongoing oscillatory activity performed to date. Critically, the identification of natural frequencies is a fundamental step towards a better understanding of the functional architecture of the human brain.

The brain time toolbox, a software library to retune electrophysiology data to brain dynamics.

Human thought is highly flexible, achieved by evolving patterns of brain activity across groups of cells. Neuroscience aims to understand cognition in the brain by analysing these intricate patterns. We argue that this goal is impeded by the time format of our data-clock time. The brain is a system with its own dynamics and regime of time, with no intrinsic concern for the human-invented second. Here, we present the Brain Time Toolbox, a software library that retunes electrophysiology data in line with oscillations that orchestrate neural patterns of cognition. These oscillations continually slow down, speed up and undergo abrupt changes, introducing a disharmony between the brain's internal regime and clock time. The toolbox overcomes this disharmony by warping the data to the dynamics of coordinating oscillations, setting oscillatory cycles as the data's new time axis. This enables the study of neural patterns as they unfold in the brain, aiding neuroscientific enquiry into dynamic cognition. In support of this, we demonstrate that the toolbox can reveal results that are absent in a default clock time format.

Suppression of alpha-band power underlies exogenous attention to emotional distractors.

Alpha-band oscillations (8-14 Hz) are essential for attention and perception processes by facilitating the selection of relevant information. Directing visuospatial endogenous (voluntary) attention to a given location consistently results in a power suppression of alpha activity over occipito-parietal areas contralateral to the attended visual field. In contrast, the neural oscillatory dynamics underlying the involuntary capture of attention, or exogenous attention, are currently under debate. By exploiting the inherent capacity of emotionally salient visual stimuli to capture attention, we aimed to investigate whether exogenous attention is characterized by either a reduction or an increase in alpha-band activity. Electroencephalographic activity was recorded while participants completed a Posner visuospatial cueing task, in which a lateralized image with either positive, negative, or neutral emotional content competed with a target stimulus presented in the opposite hemifield. Compared with trials with no distractors, alpha power was reduced over occipital regions contralateral to distracting images. This reduction of alpha activity turned out to be functionally relevant, as it correlated with impaired behavioral performance on the ongoing task and was enhanced for distractors with negative valence. Taken together, our results demonstrate that visuospatial exogenous attention is characterized by a suppression of alpha-band activity contralateral to distractor location, similar to the oscillatory underpinnings of endogenous attention. Further, these results highlight the key role of exogenous attention as an adaptive mechanism for the efficient detection of biologically salient stimuli.

PTGDR2 Expression in Peripheral Blood as a Potential Biomarker in Adult Patients with Asthma.

BACKGROUND: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. METHODS: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. RESULTS: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients' peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. CONCLUSIONS: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.

Cocamidopropyl Betaine Surfactant 0.075% Solution in Physiological Serum for Hygiene Process of COVID-19 Intubated Patients.

When using ventilators in the management of the coronavirus disease 2019 patient, dense and abundant mucous secretions are formed, obstructing the endotracheal tube and making its aspiration difficult. This situation is worsened if in order to minimize the risk of infection of the medical personnel, the humidifier is disconnected. This circumstance forces the tube to be removed, cleaned, or changed, increasing the workload of the intensive care unit staff. Other therapies tested until now, like mesna, acetylcysteine, or hypertonic saline solution, are valid alternatives, although they have not shown great efficacy for this specific procedure in the past. The sanitary emergency forced the collaboration between a pharmacist and an otorhinolaryngologist to develop the cocamidopropyl betaine surfactant formula, after several tests with different concentrations of the surfactant. The objective of this compounding formula was to resolve a mechanical problem and avoid reintubation due to obstruction of the ventilator tube. The cocamidopropyl betaine surfactant solution 0.075% in saline 0.9% (physiological serum) solution demonstrated to be a well-tolerated formula, using inexpensive materials, was simple to prepare, and was easy to use in clinical practice.

The 'Narcissus Effect': Top-down alpha-beta band modulation of face-related brain areas during self-face processing.

Self-related information, such as one's own face, is prioritized by our cognitive system. Whilst recent theoretical developments suggest that this is achieved by an interplay between bottom-up and top-down attentional mechanisms, their underlying neural dynamics are still poorly understood. Furthermore, it is still matter of discussion as to whether these attentional mechanisms are truly self-specific or instead driven by face familiarity. To address these questions, we used EEG to record the brain activity of twenty-five healthy participants whilst identifying their own face, a friend's face and a stranger's face. Time-frequency analysis revealed a greater sustained power decrease in the alpha and beta frequency bands for the self-face, which emerged at late latencies and was maintained even when the face was no longer present. Critically, source analysis showed that this activity was generated in key brain regions for self-face recognition, such as the fusiform gyrus. As in the Myth of Narcissus, our results indicate that one's own face might have the potential to hijack attention. We suggest that this effect is specific to the self and driven by a top-down attentional control mechanism, which might facilitate further processing of personally relevant events.

Is your own face more than a highly familiar face?

This study aimed to elucidate whether distinct early processes underlie the perception of our own face. Alternatively, self-face perception might rely on the same processes that realize the perception of highly familiar faces. To this end, we recorded EEG activity while participants performed a facial recognition task in which they had to discriminate between their own face, a friend's face, and an unknown face. We analyzed the event-related potentials (ERPs) to characterize the time course of neural processes involved in different stages of self-face recognition. Our results show that the N170 component was not sensitive to self-face. In contrast, the subsequent P200 component distinguished between self-face and the other faces. Finally, N250 amplitude increased as a function of face familiarity. Overall, our data suggest that self-face recognition neither emerges at the first stage of the encoding of facial information nor at a later stage when familiarity is processed. Rather, the distinctive processing of self-face arises at an intermediate stage (˜200 ms), as indicated by a lower P200 amplitude. This could be taken as an indicator that self-face recognition is facilitated by a reduced need for attentional resources. In sum, our results suggest that self-face is more than a highly familiar face.

Retinotopic mapping of visual event-related potentials.

Visual stimulation is frequently employed in electroencephalographic (EEG) research. However, despite its widespread use, no studies have thoroughly evaluated how the morphology of the visual event-related potentials (ERPs) varies according to the spatial location of stimuli. Hence, the purpose of this study was to perform a detailed retinotopic mapping of visual ERPs. We recorded EEG activity while participants were visually stimulated with 60 pattern-reversing checkerboards placed at different polar angles and eccentricities. Our results show five pattern-reversal ERP components. C1 and C2 components inverted polarity between the upper and lower hemifields. P1 and N1 showed higher amplitudes and shorter latencies to stimuli located in the contralateral lower quadrant. In contrast, P2 amplitude was enhanced and its latency was reduced by stimuli presented in the periphery of the upper hemifield. The retinotopic maps presented here could serve as a guide for selecting optimal visuo-spatial locations in future ERP studies.

Leiomiosarcoma radioinducido de la región posterior del cuello / Radiation-induced leiomyosarcoma of the posterior neck region

Los leiomiosarcomas son tumores mesenquimales malignos, que se originan en las células del músculo liso. Las localizaciones de aparición más frecuentes son el miometrio y el tracto gastrointestinal. En la región de cabeza y cuello los leiomiosarcomas aparecen de forma excepcional. Presentamos el caso de un leiomiosarcoma en la región posterior del cuello, en un paciente radiado 20 años antes por un tumor de nasofaringe. La incidencia de este tipo de tumores que cumple los criterios de tumor radioinducido se sitúa entre el 0,035 y el 0,2%. Los sarcomas radioinducidos son difíciles de diagnosticar en estadios tempranos, debido a la induración y la fibrosis de la zona radiada y a la sintomatología inespecífica que presentan. Su pronóstico es malo (AU)

Leiomyosarcomas are mesenchymal malignant tumours that appear in smooth muscle cells. Their most frequent locations are the uterus and gastrointestinal tract. Their occurrence in head and neck is considered exceptional. We present a patient with a posterior neck region leiomyosarcoma who had received radiation for a nasopharyngeal carcinoma 20 years earlier. The incidence ratio of these tumours in radiated patients (therefore considered radiation-induced) ranges from 0,035 to 0,2%. Radiation-induced sarcomas are difficult to diagnose due to the induration and fibrosis in the radiated area and the non-specific symptoms that they present. Their prognosis is very poor (AU)

Radiation-induced leiomyosarcoma of the posterior neck region.

INTRODUCTION: Leiomyosarcomas are mesenchymal malignant tumours that appear in smooth muscle cells. Their most frequent locations are the uterus and gastrointestinal tract. Their occurrence in head and neck is considered exceptional. We present a patient with a posterior neck region leiomyosarcoma who had received radiation for a nasopharyngeal carcinoma 20 years earlier. The incidence ratio of these tumours in radiated patients (therefore considered radiation-induced) ranges from 0,035 to 0,2%. Radiation-induced sarcomas are difficult to diagnose due to the induration and fibrosis in the radiated area and the non-specific symptoms that they present. Their prognosis is very poor.

Complicaciones de la cirugía endoscópica nasosinusal en un programa de entrenamiento de residentes / Complications of endoscopic sinus surgery in a residency training program

Introducción: La cirugía endoscopica nasosinusal presenta una serie de complicaciones que varían en función de la técnica usada y la experiencia del cirujano. Esta técnica requiere una curva de aprendizaje la cual se debe ir desarrollando a lo largo del programa de formación del residente. Métodos: Estudio descriptivo y retrospectivo, se realizó una revisión de las historias clínicas de 192 pacientes intervenidos de cirugía endoscopica por poliposis nasosinusal, todas estas cirugías fueron realizadas por residentes de nuestro departamento, entre enero de 2002 y enero de 2008. Se describe el sexo, edad, grado de poliposis, complicaciones mayores y menores. Todos estos procedimientos fueron realizados por residentes de 3.er y 4.° año bajo la supervisión de un especialista. Resultados: De 192 pacientes, 127 (66,14) eran varones y 65 (33,85%) mujeres, con edades comprendidas entre 24 y 78 años, con una media de edad de 49 años. El grado de poliposis por endoscopia era: grado i 19 (9,8%), grado ii 55 (28,6%) y grado iii 118 (61,45%). Ocurrieron 44 (22,9%) complicaciones totales, 40 (20,8%) menores y 4 (2,08%) mayores. La complicación menor mas frecuente fue la sinequia en 21 casos (10,93%) seguida de sangrado sin necesidad de transfusión en 12 (6,25%) pacientes. La complicación mayor fue ruptura de la lamina papiracea en 4 (2,08%) pacientes. No se presentó ningún caso de ceguera, rinolicuorrea, o muerte. Conclusión: La cirugía endoscopica nasosinusal en un programa de entrenamiento de residentes es un procedimiento relativamente seguro especialmente cuando se realiza bajo la supervisión de un especialista (AU)

Introduction: Endoscopic sinus surgery presents a series of complications that can vary depending on the technique used and the surgeon's experience. This technique needs a learning curve, which must be developed during the residence training program. Methods: Descriptive and retrospective study, reviewing the medical records of endoscopic sinus surgery for nasal polyps of 192 patients who had undergone operations performed by residents at our department between January 2002 and January 2008. Patient sex, age, affectation scale and minor and major complications were described. All these procedures were performed by 3rd or 4th-year residents under the supervision of a faculty member. Results: Of the 192 patients, 127 (66.14%) were male and 65 (33.85%) female, aged between 24 and 78 years old, with a mean age of 49 years old. Nasal endoscopy revealed polyposis of grade I, 19 (9.8%) cases; grade II, 55 (28.6%); and grade III, 118 (61.45%). There were 44 (22.9%) total complications, 40 (20.8%) minor and 4 (2.08%) major complications. The most common minor complication was synechia formation in 21 (10.93%) cases, followed by bleeding without need for transfusion in 12 (6.25%). The major complication was a breach of the lamina papyracea in 4 patients (2.08%). There were no cases of blindness, cerebrospinal fluid rhinorrhea, or death. Conclusions: Endoscopic sinus surgery in an otolaryngology residency training program is a relatively safe procedure, especially when performed under faculty supervision (AU)

[Complications of endoscopic sinus surgery in a residency training program]. / Complicaciones de la cirugía endoscópica nasosinusal en un programa de entrenamiento de residentes.

INTRODUCTION: Endoscopic sinus surgery presents a series of complications that can vary depending on the technique used and the surgeon's experience. This technique needs a learning curve, which must be developed during the residence training program. METHODS: Descriptive and retrospective study, reviewing the medical records of endoscopic sinus surgery for nasal polyps of 192 patients who had undergone operations performed by residents at our department between January 2002 and January 2008. Patient sex, age, affectation scale and minor and major complications were described. All these procedures were performed by 3rd or 4th-year residents under the supervision of a faculty member. RESULTS: Of the 192 patients, 127 (66.14%) were male and 65 (33.85%) female, aged between 24 and 78 years old, with a mean age of 49 years old. Nasal endoscopy revealed polyposis of grade i, 19 (9.8%) cases; grade ii, 55 (28.6%); and grade iii, 118 (61.45%). There were 44 (22.9%) total complications, 40 (20.8%) minor and 4 (2.08%) major complications. The most common minor complication was synechia formation in 21(10.93%) cases, followed by bleeding without need for transfusion in 12 (6.25%). The major complication was a breach of the lamina papyracea in 4 patients (2.08%). There were no cases of blindness, cerebrospinal fluid rhinorrhea, or death. CONCLUSIONS: Endoscopic sinus surgery in an otolaryngology residency training program is a relatively safe procedure, especially when performed under faculty supervision.