ENIGMA's simple seven: Recommendations to enhance the reproducibility of resting-state fMRI in traumatic brain injury.

Resting state functional magnetic resonance imaging (rsfMRI) provides researchers and clinicians with a powerful tool to examine functional connectivity across large-scale brain networks, with ever-increasing applications to the study of neurological disorders, such as traumatic brain injury (TBI). While rsfMRI holds unparalleled promise in systems neurosciences, its acquisition and analytical methodology across research groups is variable, resulting in a literature that is challenging to integrate and interpret. The focus of this narrative review is to address the primary methodological issues including investigator decision points in the application of rsfMRI to study the consequences of TBI. As part of the ENIGMA Brain Injury working group, we have collaborated to identify a minimum set of recommendations that are designed to produce results that are reliable, harmonizable, and reproducible for the TBI imaging research community. Part one of this review provides the results of a literature search of current rsfMRI studies of TBI, highlighting key design considerations and data processing pipelines. Part two outlines seven data acquisition, processing, and analysis recommendations with the goal of maximizing study reliability and between-site comparability, while preserving investigator autonomy. Part three summarizes new directions and opportunities for future rsfMRI studies in TBI patients. The goal is to galvanize the TBI community to gain consensus for a set of rigorous and reproducible methods, and to increase analytical transparency and data sharing to address the reproducibility crisis in the field.

Improving quantitative susceptibility mapping for the identification of traumatic brain injury neurodegeneration at the individual level.

BACKGROUND: Emerging evidence suggests that traumatic brain injury (TBI) is a major risk factor for developing neurodegenerative disease later in life. Quantitative susceptibility mapping (QSM) has been used by an increasing number of studies in investigations of pathophysiological changes in TBI. However, generating artefact-free quantitative susceptibility maps in brains with large focal lesions, as in the case of moderate-to-severe TBI (ms-TBI), is particularly challenging. To address this issue, we utilized a novel two-pass masking technique and reconstruction procedure (two-pass QSM) to generate quantitative susceptibility maps (QSMxT; Stewart et al., 2022, Magn Reson Med.) in combination with the recently developed virtual brain grafting (VBG) procedure for brain repair (Radwan et al., 2021, NeuroImage) to improve automated delineation of brain areas. We used QSMxT and VBG to generate personalised QSM profiles of individual patients with reference to a sample of healthy controls. METHODS: Chronic ms-TBI patients (N = 8) and healthy controls (N = 12) underwent (multi-echo) GRE, and anatomical MRI (MPRAGE) on a 3T Siemens PRISMA scanner. We reconstructed the magnetic susceptibility maps using two-pass QSM from QSMxT. We then extracted values of magnetic susceptibility in grey matter (GM) regions (following brain repair via VBG) across the whole brain and determined if they deviate from a reference healthy control group [Z-score < -3.43 or > 3.43, relative to the control mean], with the aim of obtaining personalised QSM profiles. RESULTS: Using two-pass QSM, we achieved susceptibility maps with a substantial increase in quality and reduction in artefacts irrespective of the presence of large focal lesions, compared to single-pass QSM. In addition, VBG minimised the loss of GM regions and exclusion of patients due to failures in the region delineation step. Our findings revealed deviations in magnetic susceptibility measures from the HC group that differed across individual TBI patients. These changes included both increases and decreases in magnetic susceptibility values in multiple GM regions across the brain. CONCLUSIONS: We illustrate how to obtain magnetic susceptibility values at the individual level and to build personalised QSM profiles in ms-TBI patients. Our approach opens the door for QSM investigations in more severely injured patients. Such profiles are also critical to overcome the inherent heterogeneity of clinical populations, such as ms-TBI, and to characterize the underlying mechanisms of neurodegeneration at the individual level more precisely. Moreover, this new personalised QSM profiling could in the future assist clinicians in assessing recovery and formulating a neuroscience-guided integrative rehabilitation program tailored to individual TBI patients.

Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial.

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Reversible hyperintensity in middle cerebellar peduncles. An infrequent finding in Marchiafava-Bignami disease. / Hiperintensidad reversible en los pedúnculos cerebelosos medios. Un hallazgo infrecuente en la enfermedad de Marchiafava-Bignami.

TITLE: Hiperintensidad reversible en los pedúnculos cerebelosos medios. Un hallazgo infrecuente en la enfermedad de Marchiafava-Bignami.

Experiencia de 20 años en el control de la hipertensión arterial en un centro de salud en España: control estricto versus no estricto / Twenty-year experience in strict versus non-strict control of arterial hypertension in a health center in Spain

Introducción y objetivos En los ensayos clínicos la reducción eficaz de la presión arterial (PA) produce una disminución de la incidencia de la morbimortalidad cardiovascular (CV). Nuestro objetivo principal es conocer si en las condiciones reales de la práctica clínica el control de la PA reduce a largo plazo los eventos CV. Pacientes y métodos El estudio se realizó en 164 pacientes con hipertensión arterial (HTA) elegidos entre los pacientes que acudían a las consultas de medicina de familia por HTA. Se hizo un análisis entre los pacientes que presentaban una PA clínica inferior a 140/90mmHg y los que la tenían más elevada. Los pacientes se seguían hasta que se producía un evento CV o hasta un máximo de 20 años, en que se finalizaba el seguimiento. Resultados Del total de los 164 pacientes alcanzaron un buen control clínico de la HTA 93 (56,7%) pacientes y no lo alcanzaron 71 (42,2%). En el análisis multivariante quedó únicamente como variable predictora de eventos CV la falta de control estricto de la HTA (HR: 2,93; IC 95%: 1,45-5,89; p=0,003), y el sexo femenino fue protector para eventos CV (HR: 0,37; IC 95%: 0,18-0,74; p=0,005) Conclusiones La variable predictora fundamental de morbimortalidad CV en pacientes con HTA es la falta de control estricto de la HTA; las mujeres también tuvieron menos complicaciones CV (AU)

Introduction and aims During clinical trials effective reduction of blood pressure (BP) leads to a reduction in the incidence of cardiovascular (CV) morbimortality. Our main aim is to ascertain whether, under actual conditions of clinical practice, BP monitoring leads to a long-term reduction in CV events. Patients and methods The study was performed on 164 patients with hypertension (HT) selected among patients who came to family medicine consultations because of HT. An analysis was performed between patients who presented clinical BP lower than 140/90mmHg and those that had higher levels. When patients entered the study, they were followed up until a CV event occurred or up to a maximum of 20 years, at which time follow up ended. Results Of the total of 164 patients, good control of BP was attained by 93 (56.7%), and 71 did not attain good control (42.2%). In the multivariate analysis, the only predictive variable for CV events was the lack of strict control of BP (HR: 2.93; 95% CI: 1.45-5.89; p=0.003), and the female sex was protective for CV events (HR: 0.37; 95% CI: 0.18-0.74; p=0.005). Conclusions The fundamental predictor variable of CV morbimortality in patients with HT is the lack of HT strict control; the women also had fewer CV complications (AU)

[Twenty-year experience in strict versus non-strict control of arterial hypertension in a health center in Spain]. / Experiencia de 20 años en el control de la hipertensión arterial en un centro de salud en España: control estricto versus no estricto.

INTRODUCTION AND AIMS: During clinical trials effective reduction of blood pressure (BP) leads to a reduction in the incidence of cardiovascular (CV) morbimortality. Our main aim is to ascertain whether, under actual conditions of clinical practice, BP monitoring leads to a long-term reduction in CV events. PATIENTS AND METHODS: The study was performed on 164 patients with hypertension (HT) selected among patients who came to family medicine consultations because of HT. An analysis was performed between patients who presented clinical BP lower than 140/90mmHg and those that had higher levels. When patients entered the study, they were followed up until a CV event occurred or up to a maximum of 20 years, at which time follow up ended. RESULTS: Of the total of 164 patients, good control of BP was attained by 93 (56.7%), and 71 did not attain good control (42.2%). In the multivariate analysis, the only predictive variable for CV events was the lack of strict control of BP (HR: 2.93; 95% CI: 1.45-5.89; p=0.003), and the female sex was protective for CV events (HR: 0.37; 95% CI: 0.18-0.74; p=0.005). CONCLUSIONS: The fundamental predictor variable of CV morbimortality in patients with HT is the lack of HT strict control; the women also had fewer CV complications.

Individualised profiling of white matter organisation in moderate-to-severe traumatic brain injury patients.

BACKGROUND AND PURPOSE: Approximately 65% of moderate-to-severe traumatic brain injury (m-sTBI) patients present with poor long-term behavioural outcomes, which can significantly impair activities of daily living. Numerous diffusion-weighted MRI studies have linked these poor outcomes to decreased white matter integrity of several commissural tracts, association fibres and projection fibres in the brain. However, most studies have focused on group-based analyses, which are unable to deal with the substantial between-patient heterogeneity in m-sTBI. As a result, there is increasing interest and need in conducting individualised neuroimaging analyses. MATERIALS AND METHODS: Here, we generated a detailed subject-specific characterisation of microstructural organisation of white matter tracts in 5 chronic patients with m-sTBI (29 - 49y, 2 females), presented as a proof-of-concept. We developed an imaging analysis framework using fixel-based analysis and TractLearn to determine whether the values of fibre density of white matter tracts at the individual patient level deviate from the healthy control group (n = 12, 8F, Mage = 35.7y, age range 25 - 64y). RESULTS: Our individualised analysis revealed unique white matter profiles, confirming the heterogenous nature of m-sTBI and the need of individualised profiles to properly characterise the extent of injury. Future studies incorporating clinical data, as well as utilising larger reference samples and examining the test-retest reliability of the fixel-wise metrics are warranted. CONCLUSIONS: Individualised profiles may assist clinicians in tracking recovery and planning personalised training programs for chronic m-sTBI patients, which is necessary to achieve optimal behavioural outcomes and improved quality of life.

Sport fishing and vessel pressure on the endangered cetacean Delphinus delphis. Towards an international agreement of micro-sanctuary for its conservation.

Delphinus delphis Linnaeus 1758 is considered an endangered species in the Mediterranean. The species is resident in the Bay of Algeciras - Gibraltar (southern Spain; waters partially shared with Gibraltar, UK). This area is subject to strong anthropogenic pressure, but with an input of renewed waters in its central area. During three consecutive years (March 2017-March 2020), sightings were observed concentrated along the submarine canyon that runs north to south across the bay, forming a "specular S″ with a maximum depth of 460 m. The pods of Dd showed a continuous or semi-continuous spatial distribution along the vertical axis of the submarine canyon, where they feed, mate, breed and rear calves in a well-defined area that constitutes a critical habitat. This area has been cartographically delimited, choosing the area of maximum dolphin frequency as highly vulnerable due to the possibility of collisions with small vessels (<15 m) and interactions with sport fishing activities (popping, ballooning, trolling) which constitute the main threat counting the derived impacts from noise pollution. Spatio-temporal mapping has been developed to visualize the overlapping between the dolphin groups and small vessels. Mapping analysis has shown that an international Spanish-British micro-sanctuary urgently needs to be established in order to create a protected area specifically for the common dolphins, and for other species which inhabit/use the waters between Spain and Gibraltar. Coordinates and a delimited surface area have been proposed in this paper.

Structural-functional connectivity bandwidth of the human brain.

BACKGROUND: The human brain is a complex network that seamlessly manifests behaviour and cognition. This network comprises neurons that directly, or indirectly mediate communication between brain regions. Here, we show how multilayer/multiplex network analysis provides a suitable framework to uncover the throughput of structural connectivity (SC) to mediate information transfer-giving rise to functional connectivity (FC). METHOD: We implemented a novel method to reconcile SC and FC using diffusion and resting-state functional MRI connectivity data from 484 subjects (272 females, 212 males; age = 29.15 ± 3.47) from the Human Connectome Project. First, we counted the number of direct and indirect structural paths that mediate FC. FC nodes with indirect SC paths were then weighted according to their least restrictive SC path. We refer to this as SC-FC Bandwidth. We then mapped paths with the highest SC-FC Bandwidth across 7 canonical resting-state networks. FINDINGS: We found that most pairs of FC nodes were connected by SC paths of length two and three (SC paths of length >5 were virtually non-existent). Direct SC-FC connections accounted for only 10% of all SC-FC connections. The majority of FC nodes without a direct SC path were mediated by a proportion of two (44%) or three SC path lengths (39%). Only a small proportion of FC nodes were mediated by SC path lengths of four (5%). We found high-bandwidth direct SC-FC connections show dense intra- and sparse inter-network connectivity, with a bilateral, anteroposterior distribution. High bandwidth SC-FC triangles have a right superomedial distribution within the somatomotor network. High-bandwidth SC-FC quads have a superoposterior distribution within the default mode network. CONCLUSION: Our method allows the measurement of indirect SC-FC using undirected, weighted graphs derived from multimodal MRI data in order to map the location and throughput of SC to mediate FC. An extension of this work may be to explore how SC-FC Bandwidth changes over time, relates to cognition/behavior, and if this measure reflects a marker of neurological injury or psychiatric disorders.

Effects of the Response to the COVID-19 Pandemic on Assault-Related Head Injury in Melbourne: A Retrospective Study.

Assault is the leading preventable cause of death, traumatic brain injury (TBI), and associated mental health problems. The COVID-19 pandemic has had a profound impact on patterns of interpersonal violence across the world. In this retrospective cross-sectional study, we analysed medical records of 1232 assault victims (domestic violence: 111, random assault: 900, prison assault: 221) with head injuries who presented to the emergency department (ED) at St Vincent's Hospital in Melbourne, Australia, a city with one of the longest and most severe COVID-19 restrictions worldwide. We examined changes in prevalence in the assault group overall and in domestic violence, random assault, and prison assault victims, comparing data from 19.5 months before and after the first day of COVID-19 restrictions in Melbourne. Moreover, we investigated differences driven by demographic factors (Who: age group, sex, and nationality) and clinical variables (Where: assault location, and When: time of arrival to the ED and time from moment of injury until presentation at ED). Descriptive statistics and chi-square analyses were performed. We found the COVID-19 pandemic significantly affected the Where of assault-related TBI, with a shift in the location of assaults from the street to the home, and the increase at home being driven by random assaults on middle-aged adults. Overall, we observed that 86% of the random assault cases were males, whereas 74% of the domestic assault cases were females. Meanwhile, nearly half (44%) of the random assault victims reported alcohol consumption versus a fifth (20%) of domestic violence victims. These findings will have direct implications for developing screening tools and better preventive and ameliorative interventions to manage the sequelae of assault TBI, particularly in the context of future large-scale health crises or emergencies.

Vitamin D supplementation and COVID-19 risk: a population-based, cohort study.

PURPOSE: To analyze the associations between cholecalciferol or calcifediol supplementation, serum 25-hydroxyvitamin D (25OHD) levels and COVID-19 outcomes in a large population. METHODS: All individuals ≥ 18 years old living in Barcelona-Central Catalonia (n = 4.6 million) supplemented with cholecalciferol or calcifediol from April 2019 to February 2020 were compared with propensity score-matched untreated controls. Outcome variables were SARS-CoV2 infection, severe COVID-19 and COVID-19 mortality occuring during the first wave of the pandemic. Demographical data, comorbidities, serum 25OHD levels and concomitant pharmacological treatments were collected as covariates. Associations between cholecalciferol or calcifediol use and outcome variables were analyzed using multivariate Cox proportional regression. RESULTS: Cholecalciferol supplementation (n = 108,343) was associated with slight protection from SARS-CoV2 infection (n = 4352 [4.0%] vs 9142/216,686 [4.2%] in controls; HR 0.95 [CI 95% 0.91-0.98], p = 0.004). Patients on cholecalciferol treatment achieving 25OHD levels ≥ 30 ng/ml had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19 and lower COVID-19 mortality than unsupplemented 25OHD-deficient patients (56/9474 [0.6%] vs 96/7616 [1.3%]; HR 0.66 [CI 95% 0.46-0.93], p = 0.018). Calcifediol use (n = 134,703) was not associated with reduced risk of SARS-CoV2 infection or mortality in the whole cohort. However, patients on calcifediol treatment achieving serum 25OHD levels ≥ 30 ng/ml also had lower risk of SARS-CoV2 infection, lower risk of severe COVID-19, and lower COVID-19 mortality compared to 25OHD-deficient patients not receiving vitamin D supplements (88/16276 [0.5%] vs 96/7616 [1.3%]; HR 0.56 [CI 95% 0.42-0.76], p < 0.001). CONCLUSIONS: In this large, population-based study, we observed that patients supplemented with cholecalciferol or calcifediol achieving serum 25OHD levels ≥ 30 ng/ml were associated with better COVID-19 outcomes.

Analysis of body condition indices reveals different ecotypes of the Antillean manatee.

Assessing the body condition of wild animals is necessary to monitor the health of the population and is critical to defining a framework for conservation actions. Body condition indices (BCIs) are a non-invasive and relatively simple means to assess the health of individual animals, useful for addressing a wide variety of ecological, behavioral, and management questions. The Antillean manatee (Trichechus manatus manatus) is an endangered subspecies of the West Indian manatee, facing a wide variety of threats from mostly human-related origins. Our objective was to define specific BCIs for the subspecies that, coupled with additional health, genetic and demographic information, can be valuable to guide management decisions. Biometric measurements of 380 wild Antillean manatees captured in seven different locations within their range of distribution were obtained. From this information, we developed three BCIs (BCI1 = UG/SL, BCI2 = W/SL3, BCI3 = W/(SL*UG2)). Linear models and two-way ANCOVA tests showed significant differences of the BCIs among sexes and locations. Although our three BCIs are suitable for Antillean manatees, BCI1 is more practical as it does not require information about weight, which can be a metric logistically difficult to collect under particular circumstances. BCI1 was significantly different among environments, revealing that the phenotypic plasticity of the subspecies have originated at least two ecotypes-coastal marine and riverine-of Antillean manatees.

Central vein sign: A diagnostic biomarker in multiple sclerosis (CAVS-MS) study protocol for a prospective multicenter trial.

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the North American Imaging in MS Cooperative (NAIMS) to evaluate CVS as a diagnostic biomarker for immediate translation into clinical care. Study objectives include determining the concordance of CVS and McDonald Criteria to diagnose MS, the sensitivity of CVS to detect MS in those with typical presentations, and the specificity of CVS among those with atypical presentations. The study will recruit a total of 400 participants (200 with typical and 200 with atypical presentations) across 11 sites. T2*-weighted, high-isotropic-resolution, segmented echo-planar MRI will be acquired at baseline and 24 months on 3-tesla scanners, and FLAIR* images (combination of FLAIR and T2*) will be generated for evaluating CVS. Data will be processed on a cloud-based platform that contains clinical and CVS rating modules. Imaging quality control will be conducted by automated methods and neuroradiologist review. CVS will be determined by Select6* and Select3* lesion methods following published criteria at each site and by central readers, including neurologists and neuroradiologists. Automated CVS detection and algorithms for incorporation of CVS into McDonald Criteria will be tested. Diagnosis will be adjudicated by three neurologists who served on the 2017 International Panel on the Diagnosis of MS. The CAVS-MS study aims to definitively establish CVS as a diagnostic biomarker that can be applied broadly to individuals presenting for evaluation of the diagnosis of MS.