Monitoring and Prognosis System Based on the ICF for People with Traumatic Brain Injury

The objective of this research is to provide a standardized platform to monitor and predict indicators of people with traumatic brain injury using the International Classification of Functioning, Disability and Health, and analyze its potential benefits for people with disabilities, health centers and administrations. We developed a platform that allows automatic standardization and automatic graphical representations of indicators of the status of individuals and populations. We used data from 730 people with acquired brain injury performing periodic comprehensive evaluations in the years 2006-2013. Health professionals noted that the use of color-coded graphical representation is useful for quickly diagnose failures, limitations or restrictions in rehabilitation. The prognosis System achieves 41% of accuracy and sensitivity in the prediction of emotional functions, and 48% of accuracy and sensitivity in the prediction of executive functions. This monitoring and prognosis system has the potential to: (1) save costs and time, (2) provide more information to make decisions, (3) promote interoperability, (4) facilitate joint decision-making, and (5) improve policies of socioeconomic evaluation of the burden of disease. Professionals found the monitoring system useful because it generates a more comprehensive understanding of health oriented to the profile of the patients, instead of their diseases and injuries

Diffusion-Weighted Magnetic Resonance Imaging in Peritoneal Carcinomatosis from Ovarian Cancer: Diagnostic performance in correlation with surgical findings.

Purpose Ovarian cancer (OC) is the commonest cause of death by gynaecological cancer in developed countries. Peritoneal carcinomatosis (PC) complete debulking without residual disease of >1 cm is the best prognostic predictor in advanced OC. PC is assessed with Computed tomography (CT). CT accuracy and cytoreduction success predictive ability are limited. PET/CT is not an imaging standard for PC. PC shows high signal foci in Diffusion-weighted magnetic resonance imaging (DWI MRI). We assessed the diagnostic performance (DP) and tumour burden correlation of Whole body DWI with background suppression MRI (WB-DWIBS/MRI) in PC of suspected OC using the Peritoneal Cancer Index (PCI), referring to cytoreduction surgery as the standard reference. Method Fifty patients with suspicion of disseminated OC underwent cytoreduction and WB-DWIBS/MRI. The PCI scores tumour burden (0–3) in 13 anatomical regions (global range of 0–39). Two radiologists (Rad1/Rad2) assessed the PCI preoperatively and with surgical findings. We evaluated regional and global DP, the interobserver agreement (Cohen´s kappa coefficient), statistical differences (McNemar test) and tumour burden (Pearson’s test). Results 72% (36/50) were epithelial OC and 78% (39/50) achieved complete cytoreduction. Global-PCI correlation was 0.762 (Rad1) with DP: Sensitivity 0.84, specificity 0.89, accuracy 0.89, and kappa 0.41. Average global-PCI was 7. The pelvis and right hypochondrium showed the highest positive rate and DP, while the intestinal regions presented the lowest. Previous studies reported higher sensitivity than CT or PET/CT, although only a few used the PCI. Conclusions WB-DWIBS/MRI is reliable to depict, quantify and to predict complete cytoreductive surgery in OC PC.pre-print2737 K

Application of Lipid Class Ratios for Sample Stability Monitoring—Evaluation of Murine Tissue Homogenates and SDS as a Stabilizer

Lipids are a ubiquitous class of structurally complex molecules involved in various biological processes. In the fast-growing field of lipidomics, preanalytical issues are frequently neglected. Here, we investigated the stability of lipid profiles of murine liver, brain, lung, heart, and spleen homogenates by quantitative flow injection analysis using tandem mass spectrometry and high-resolution mass spectrometry. Storage of tissue homogenates at room temperature showed substantial alterations of the lipid profiles reflecting lipolytic action. Therefore, ratios of ceramide to sphingomyelin, lysophosphatidylethanolamine to phosphatidylethanolamine, lysophosphatidylcholine to phosphatidylcholine, and diglyceride to triglyceride were applied to monitor sample stability and the effect of sodium dodecyl sulfate (SDS) as a potential stabilizing agent. The addition of SDS led to a concentration-dependent stabilization of lipid profiles in liver, brain, and heart homogenates, while in lung and spleen homogenates, in particular, the lysophosphatidylethanolamine to phosphatidylethanolamine ratio increased upon addition of SDS. In conclusion, we demonstrated that lipid class ratios reflecting lipolytic activity could be applied to evaluate both the stability of samples and the influence of stabilizers

The impact of ABCDE bundle implementation on patient outcomes: a nationwide cohort study

Background: The ABCDE bundle is a set of evidence-based practices to systematically reduce the risks of sedation, delirium, and immobility in intensive care patients. Implementing the bundle improves clinical outcome. Aims and Objectives: To investigate the association between patient outcomes and compliance with bundle components ABC (analgosedation algorithms), D (delirium protocol), and E (early mobilization protocol). Design: A Spanish multicentre cohort study of adult patients receiving invasive mechanical ventilation (IMV) for ≥48 h until extubation. Methods: The primary outcome was pain level, cooperation to permit Medical Research Council Scale administration, patient days of delirium, and mobility. The secondary outcome was cumulative drug dosing by IMV days. Tertiary outcomes (ICU days, IMV days, bed rest days, ICU mortality, ICUAW) and independent variables (analgosedation, delirium, early mobilization protocols) were also studied. Results: Data were collected from 605 patients in 80 ICUs and 5214 patient days with IMV. Two-thirds of the ICUs studied applied no protocols. Pain was not assessed on 83.6% of patient days. Patient cooperation made scale administration feasible on 20.7% of days. Delirium and immobility were found on 4.2% and 69.9% of days, respectively. Patients had shorter stays in ICUs with bundle protocols and fewer days of IMV in ICUs with delirium and mobilization bundle components (P = 0.006 and P = 0.03, respectively). Analgosedation protocols were associated with more opioid dosing (P = 0.02), and delirium and early mobilization protocols with more propofol (P = 0.001), dexmedetomidine (P = 0.001), and lower benzodiazepine dosing (P = 0.008). Conclusions: The implementation rate of ABCDE bundle components was very low in our Spanish setting, but when implemented, patients had a shorter ICU stay, more analgesia dosing, and lighter sedation. Relevance to clinical practice: Applying some but not all the bundle components, there is increased analgesia and light sedation drug use, decreased benzodiazepines, and increased patient cooperation and mobility, resulting in a shorter ICU stay and fewer days of IMV

Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis

Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment. We find that CXCL10 is upregulated in metastasis-associated astrocytes in mice and humans and is functionally important for the chemoattraction of melanoma cells. Moreover, CXCR3, the receptor for CXCL10, is upregulated in brain-tropic melanoma cells. Targeting melanoma expression of CXCR3 by nanoparticle-mediated siRNA delivery or by shRNA transduction inhibits melanoma cell migration and attenuates brain metastasis in vivo. These findings suggest that the instigation of pro-inflammatory signaling in astrocytes is hijacked by brain-metastasizing tumor cells to promote their metastatic capacity and that the CXCL10-CXCR3 axis may be a potential therapeutic target for the prevention of melanoma brain metastasis

Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol

Aims: To assess the impact of the COVID-19 pandemic on the health condition of people >= 75 years of age and on their family caregivers in Spain. Design: Multicentric, mixed method concurrent study. Methods: This work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022). Discussion: The study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic. Trial Registration: Identifier: NCT05249868 [ClinicalTrials.gov]

Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain

Brain metastasis in breast cancer remains difficult to treat and its incidence is increasing. Therefore, the development of new therapies is of utmost clinical relevance. Recently, toll-like receptor (TLR) 4 was correlated with IL6 expression and poor prognosis in 1 215 breast cancer primaries. In contrast, we demonstrated that TLR4 stimulation reduces microglia-assisted breast cancer cell invasion. However, the expression, prognostic value, or therapeutic potential of TLR signaling in breast cancer brain metastasis have not been investigated. We thus tested the prognostic value of various TLRs in two brain-metastasis gene sets. Furthermore, we investigated different TLR agonists, as well as MyD88 and TRIF-deficient microenvironments in organotypic brain-slice ex vivo co-cultures and in vivo colonization experiments. These experiments underline the ambiguous roles of TLR4, its adapter MyD88, and the target nitric oxide (NO) during brain colonization. Moreover, analysis of the gene expression datasets of breast cancer brain metastasis patients revealed associations of TLR1 and IL6 with poor overall survival. Finally, our finding that a single LPS application at the onset of colonization shapes the later microglia/macrophage reaction at the macro-metastasis brain-parenchyma interface (MMPI) and reduces metastatic infiltration into the brain parenchyma may prove useful in immunotherapeutic considerations

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Impact of the COVID-19 pandemic on the self-care and health condition of the older adults. CUIDAMOS+75. A mixed methods study protocol

AimsTo assess the impact of the COVID-19 pandemic on the health condition of people ≥75 years of age and on their family caregivers in Spain.DesignMulticentric, mixed method concurrent study.MethodsThis work, which will be conducted within the primary care setting in 11 administrative regions of Spain, will include three coordinated studies with different methodologies. The first is a population-based cohort study that will use real-life data to analyze the rates and evolution of health needs, care provision, and services utilization before, during, and after the pandemic. The second is a prospective cohort study with 18 months of follow-up that will evaluate the impact of COVID-19 disease on mortality, frailty, functional and cognitive capacity, and quality of life of the participants. Finally, the third will be a qualitative study with a critical social approach to understand and interpret the social, political, and economic dimensions associated with the use of health services during the pandemic. We have followed the SPIRIT Checklist to address trial protocol and related documents. This research is being funded by the Instituto de Salud Carlos III since 2021 and was approved by its ethics committee (June 2022).DiscussionThe study findings will reveal the long-term impact of the COVID-19 pandemic on the older adults and their caregivers. This information will serve policymakers to adapt health policies to the needs of this population in situations of maximum stress, such as that produced by the COVID-19 pandemic.Trial RegistrationIdentifier: NCT05249868 [ClinicalTrials.gov]