Hidrocefalia de presión normal idiopática. Volumetría de líquido cefalorraquídeo y su correlación con el test de infusión lumbar

[ES]La hidrocefalia de presión normal idiopática (HPNi) se caracteriza por la existencia de una dilatación ventricular activa no obstructiva, asociada a una triada de síntomas característica que comprende apraxia de la marcha, trastornos urinarios y deterioro cognitivo. No se conoce etiología, aunque se han implicado mecanismos relativos a la reabsorción y pulsatilidad del líquido cefalorraquídeo (LCR), así como mecanismos de tipo isquémico. El diagnóstico es multimodal y se basa en las manifestaciones clínicas y el análisis de pruebas de neuroimagen, fundamentalmente la resonancia magnética cerebral. El tratamiento más aceptado es la derivación de LCR, siendo uno de los principales desafíos el identificar qué pacientes van a responder a dicha medida terapéutica. Para seleccionar candidatos a cirugía, se han empleado pruebas invasivas como la punción lumbar evacuadora, el drenaje lumbar externo, la monitorización de la presión intracraneal y el test de infusión lumbar con medición de la resistencia de salida del LCR (Rout). En este sentido, en los últimos años se ha prestado atención a la existencia de un compromiso de volumen en los espacios subaracnoideos de la convexidad cerebral alta y medial, asociado a una dilatación relativa de las cisuras silvianas. Este patrón morfológico, denominado ¿hidrocefalia con aumento desproporcionado del espacio subaracnoideo¿ y conocido como DESH, parece ser específico de la HPNi y asociarse a una respuesta positiva al tratamiento. Sin embargo no están claros los mecanismos por los que se produce esta desproporción, postulándose algún bloqueo suprasilviano en la circulación o en la reabsorción del LCR. Hasta el momento, no se ha demostrado dicha alteración, no existiendo actualmente publicaciones que relacionen el volumen de los compartimentos intracraneales contenedores de LCR con una resistencia elevada de salida del LCR o Rout. La hipótesis de trabajo primaria que se propone es que existe una correlación entre las proporciones de los espacios subaracnoideos intracraneales y el valor de la resistencia de salida del LCR obtenido mediante test de infusión lumbar. Se realizó un estudio retrospectivo de 45 pacientes, todos ellos sometidos a estudio diagnóstico por sospecha de hidrocefalia de presión normal idiopática durante 6 años, entre el 1 de Enero de 2008 y el 31 de Diciembre de 2014, en el Servicio de Neurocirugía del Complejo Asistencial Universitario de Salamanca. Para su inclusión en el estudio, se requirió cumplir, al menos, criterios de ¿HPNi posible¿ según las Guías Americanas y haber sido sometidos a estudio RM cerebral y pruebas de dinámica de LCR (test de infusión lumbar a volumen constante).Sobre los estudios de RM cerebral se efectuó, mediante aplicaciones informáticas una segmentación de determinados compartimentos intracraneales, obteniendo el volumen de cada uno de ellos de cara a correlaciones subsiguientes con el valor de Rout obtenido en cada paciente mediante el test de infusión lumbar. Adicionalmente se valoró la correlación de tales medidas volumétricas y variables radiológicas relacionadas con la hidrocefalia de presión normal (valor del ángulo calloso, tamaño de las astas temporales de los ventrículos laterales, vacío de señal en el acueducto de Silvio y signo del surco cingular). Por último, se examinó la relación de las medidas volumétricas con los resultados de la intervención quirúrgica mediante derivación ventrículo-peritoneal de LCR y se analizó la utilidad de incorporar dichas medidas al proceso diagnóstico de esta patología. Como resultado del estudio se concluye que: existe correlación estadísticamente significativa entre el valor de Rout y determinados valores volumétricos: un menor volumen del espacio subaracnoideo alto y medial se asocia a mayor valor de Rout, al igual que un aumento relativo del volumen de las cisuras de Silvio respecto a la talla ventricular y respecto al espacio subaracnoideo de convexidad alta y medial. Existe correlación significativa entre el valor del ángulo calloso y determinadas variables volumétricas: un menor volumen del espacio subaracnoideo alto y medial se asocia a un ángulo calloso más agudo, al igual que un aumento del volumen de las cisuras de Silvio neto y relativo a la talla ventricular y al espacio subaracnoideo de convexidad alta y medial. La presencia del surco cingular se correlacionó volumétricamente de forma similar al ángulo calloso. La anchura de las astas temporales únicamente se correlacionó con el volumen ventricular. No se detectó relación entre la presencia del signo del vacío acueductal y ninguna de las variables volumétricas examinadas. No se ha podido comprobar una relación estadísticamente significativa entre la respuesta a la derivación y las variables volumétricas examinadas. El cociente entre el volumen de las cisuras de Silvio y el espacio subaracnoideo presenta un elevado rendimiento diagnóstico, más del 88%, respecto al resultado del test de infusión lumbar. Para un punto de corte superior a 2,08, dicho cociente permite asumir un resultado positivo del test de infusión lumbar con una especificidad próxima al 100% y reclutar directamente al paciente para cirugía, según el nuevo protocolo propuesto

A rare case of stroke as a complication after percutaneous mechanical thrombectomy in a patient with intermediate-high risk pulmonary embolism and patent foramen ovale

We present an extremely rare case of a patient with intermediate-high risk pulmonary embolism treated with percutaneous mechanical thrombectomy, complicated with stroke as a form of paradoxical embolism through a previously unknown patent foramen ovale. We reviewed the literature for indications, efficacy, and safety of this procedure, as well as for experience on this technique in patients with patent foramen ovale

Impact of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients: A nationwide study in Spain

Objective To assess the effect of the first wave of the SARS-CoV-2 pandemic on the outcome of neurosurgical patients in Spain. Settings The initial flood of COVID-19 patients overwhelmed an unprepared healthcare system. Different measures were taken to deal with this overburden. The effect of these measures on neurosurgical patients, as well as the effect of COVID-19 itself, has not been thoroughly studied. Participants This was a multicentre, nationwide, observational retrospective study of patients who underwent any neurosurgical operation from March to July 2020. Interventions An exploratory factorial analysis was performed to select the most relevant variables of the sample. Primary and secondary outcome measures Univariate and multivariate analyses were performed to identify independent predictors of mortality and postoperative SARS-CoV-2 infection. Results Sixteen hospitals registered 1677 operated patients. The overall mortality was 6.4%, and 2.9% (44 patients) suffered a perioperative SARS-CoV-2 infection. Of those infections, 24 were diagnosed postoperatively. Age (OR 1.05), perioperative SARS-CoV-2 infection (OR 4.7), community COVID-19 incidence (cases/10 5 people/week) (OR 1.006), postoperative neurological worsening (OR 5.9), postoperative need for airway support (OR 5.38), ASA grade =3 (OR 2.5) and preoperative GCS 3-8 (OR 2.82) were independently associated with mortality. For SARS-CoV-2 postoperative infection, screening swab test <72 hours preoperatively (OR 0.76), community COVID-19 incidence (cases/10 5 people/week) (OR 1.011), preoperative cognitive impairment (OR 2.784), postoperative sepsis (OR 3.807) and an absence of postoperative complications (OR 0.188) were independently associated. Conclusions Perioperative SARS-CoV-2 infection in neurosurgical patients was associated with an increase in mortality by almost fivefold. Community COVID-19 incidence (cases/10 5 people/week) was a statistically independent predictor of mortality. Trial registration number CEIM 20/217

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Systematic influenza screening in cardiac intensive care units during the influenza season: A prospective study in Spain

Background: Little is known about the incidence of influenza among admissions to the cardiac intensive care unit (C-ICU), accuracy of clinical suspicion, and influenza vaccination uptake. We evaluated the incidence of influenza at C-ICU admission during the influenza season, potential underdiagnosis, and vaccination uptake. Methods: Prospective study at five C-ICUs during the 2017-2020 influenza seasons. A nasopharyngeal swab was collected at admission from patients who consented (n = 788). Testing was with Xpert®XpressFlu/RSV. Results: Influenza was detected in 43 patients (5.5%) (40 FluA; 3 FluB) and clinically suspected in 27 (62.8%). Compared to patients without influenza, patients with influenza more frequently had heart failure (37.2% vs 22.8%, P = 0.031), previous contact with relatives with influenza-like illnesses (23.3% vs 12.5%, P = 0.042), antimicrobial use (67.4% vs 23.2%, P <0.01), and need for mechanical ventilation (25.6% vs 14.5%, P = 0.048). Patients received oseltamivir promptly. We found no differences in mortality (11.6% vs 5.2%, P = 0.076). Patients with influenza more frequently had myocarditis (9.3% vs 0.9%, P <0.01) and pericarditis (7.0% vs 0.8%, P = 0.01). Overall, 43.0% of patients (339/788) were vaccinated (51.9% of those with a clear indication [303/584]). Conclusion: Influenza seems to be a frequently underdiagnosed underlying condition in admissions to the C-ICU. Influenza should be screened for at C-ICU admission during influenza epidemics

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. This was an observational retrospective study. A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)