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Measuring and interpreting individual differences in fetal, infant, and toddler neurodevelopment
No full textAs scientists interested in fetal, infant, and toddler (FIT) neurodevelopment, our research questions often focus on how individual children differ in their neurodevelopment and the predictive value of those individual differences for long-term neural and behavioral outcomes. Measuring and interpreting individual differences in neurodevelopment can present challenges: Is there a standard way for the human brain to develop? How do the semantic, practical, or theoretical constraints that we place on studying development influence how we measure and interpret individual differences? While it is important to consider these questions across the lifespan, they are particularly relevant for conducting and interpreting research on individual differences in fetal, infant, and toddler neurodevelopment due to the rapid, profound, and heterogeneous changes happening during this period, which may be predictive of long-term outcomes. This article, therefore, has three goals: 1) to provide an overview about how individual differences in neurodevelopment are studied in the field of developmental cognitive neuroscience, 2) to identify challenges and considerations when studying individual differences in neurodevelopment, and 3) to discuss potential implications and solutions moving forward
Revisiting abdominal wall morbidity of the extensile anterolateral approach to the thoracolumbar spine
No full textPURPOSE: To assess patients\u27 perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires.
METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ).
RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 ± 1.7 years. Average number of anterior fusion levels was 3.5 ± 1.4. Patients achieved high satisfaction rates from surgery (74.5%). AAIQ responses included postoperative pain (33.3%), bulging (41.7%), and limitations in daily activities (18.8%) with only 15.7% experienced moderate-severe pain related to their incisions and only 6.3% seeking treatment for their scars. Post-operatively, 63.2% had a neutral or improved self-image of their torso and trunk, while only 10.2% stating it was much worse. Patients\u27 overall opinion of their scar compared to their normal skin was very positive [average 2.75 ± 2.93 (10 = worst possible scar)]. Favorable scores were also reported for color difference, stiffness, change in thickness, and irregularity in their abdominal scar compared to normal skin.
CONCLUSIONS: Following extensile anterolateral approaches to the thoracolumbar spine for ASD, the majority of patients reported mild pain, mild functional limitations, good cosmesis, and high satisfaction rates with their anterior incisions based on validated questionnaires
Effect of telemedicine support for intraoperative anaesthesia care on postoperative outcomes: The TECTONICS randomised clinical trial
No full textBACKGROUND: Telemedicine may help improve care quality and patient outcomes. Telemedicine for intraoperative decision support has not been rigorously studied.
METHODS: This was a single-centre randomised clinical trial of unselected adult surgical patients. Patients were randomised to receive usual care or decision support from a telemedicine service, which provided real-time recommendations to intraoperative anaesthesia clinicians based on case reviews and physiological alerts. ORs were randomised 1:1. The co-primary outcomes were 30-day all-cause mortality, respiratory failure, acute kidney injury, and delirium in the intensive care unit, analysed by intention to treat.
RESULTS: Between July 1, 2019, and January 31, 2023, a total of 35,302 patients were randomised to receive telemedicine support, with 36,625 receiving usual care. Telemedicine clinicians provided review in 11,812/35,302 cases, with alerts delivered to 2044/35,302 patients. Telemedicine support had no effect on any of the co-primary outcomes. Within 30 days, 630/35,302 (1.8%) patients randomised to telemedicine died within 30 days, compared with 649/36,625 (1.8%) receiving usual care (relative risk [RR]1.01, 95% confidence interval [CI] 0.87-1.16, P=0.98). Telemedicine support did not alter postoperative respiratory failure [telemedicine 1071/33,996 (3.2%) vs usual care 1130/35,236 (3.2%), RR 0.98, 95% CI 0.88-1.09, P=0.98], acute kidney injury [telemedicine 2316/33 251 (7.0%) vs usual care 2432/34,441 (7.1%); RR 0.99, 95% CI 0.92-1.06, P=0.98], or delirium [telemedicine 1264/3873 (32.6%) vs usual care 1298/4044 (32.1%), RR 1.02, 95% CI 0.94-1.10, P=0.98].
CONCLUSIONS: In this large randomised clinical trial, intraoperative telemedicine decision support using real-time alerts and case reviews had no impact on adverse postoperative outcomes.
CLINICAL TRIAL REGISTRATION: NCT03923699
Patient selection, ventricular tachycardia substrate delineation, and data transfer for stereotactic arrhythmia radioablation: A clinical consensus statement of the European Heart Rhythm Association of the European Society of Cardiology and the Heart Rhythm Society
No full textStereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and transfer of target volume, and techniques for treatment planning and execution differ across studies, hampering the pooling of data and comparison across studies. In addition, STAR requires close and new collaboration between clinical electrophysiologists and radiation oncologists, which is facilitated by shared knowledge in each collaborator\u27s area of expertise and a common language. This clinical consensus statement provides uniform definition of cardiac target volumes. It aims to provide advice in patient selection for STAR including aetiology-specific aspects and advice in optimal cardiac target volume identification based on available evidence. Safety concerns and the advice for acute and long-term monitoring including the importance of standardized reporting and follow-up are covered by this document. Areas of uncertainty are listed, which require high-quality, reliable pre-clinical and clinical evidence before the expansion of STAR beyond clinical scenarios in which proven therapies are ineffective or unavailable
Assessing neurocognitive maturation in early adolescence based on baby and adult functional brain landscapes
No full textAdolescence is a period of growth in cognitive performance and functioning. Recently, data-driven measures of brain-age gap, which can index cognitive decline in older populations, have been utilized in adolescent data with mixed findings. Instead of using a data-driven approach, here we assess the maturation status of the brain functional landscape in early adolescence by directly comparing an individual\u27s resting-state functional connectivity (rsFC) to the canonical early-life and adulthood communities. Specifically, we hypothesized that the degree to which a youth\u27s connectome is better captured by adult networks compared to infant/toddler networks is predictive of their cognitive development. To test this hypothesis across individuals and longitudinally, we utilized the Adolescent Brain Cognitive Development (ABCD) Study at baseline (9-10 years; n = 6469) and 2-year-follow-up (Y2: 11-12 years; n = 5060). Adjusted for demographic factors, our anchored rsFC score (AFC) was associated with better task performance both across and within participants. AFC was related to age and aging across youth, and change in AFC statistically mediated the age-related change in task performance. In conclusion, we showed that a model-fitting-free index of the brain at rest that is anchored to both adult and baby connectivity landscapes predicts cognitive performance and development in youth
Innate lymphoid cells in inflammatory bowel disease
No full textInflammatory bowel disease (IBD), including Crohn\u27s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract with rising incidence and an unclear etiology. Innate lymphoid cells (ILCs) have recently emerged as key regulators of mucosal immunity and tissue homeostasis and are increasingly implicated in IBD. Unlike adaptive lymphocytes, ILCs do not require antigen recognition and clonal expansion to respond rapidly to environmental cues and shape immune responses. In a healthy gut, ILCs maintain intestinal homeostasis by guarding the epithelial barrier, protecting against pathogens, and mounting proper responses to external insults. However, their altered differentiation, proliferation, recruitment, activation, and interaction with other host cells, microbiota, and environmental stimuli may contribute to IBD. In this review, we discuss recent advances in understanding murine and human ILCs in the context of intestinal inflammation and IBD. A deeper understanding of ILC-mediated immune mechanisms may offer novel therapeutic strategies for restoring intestinal homeostasis and improving personalized management of IBD
Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension
Full text linkHeart failure with preserved ejection fraction (HFpEF) is increasingly common but its pathogenesis is poorly understood. The ability to assess genetic and pharmacologic interventions is hampered by the lack of robust preclinical mouse models of HFpEF. We developed a novel two-hit model, which combines obesity and insulin resistance with chronic pressure overload to recapitulate clinical features of HFpEF. C57Bl6/NJ mice fed a high-fat diet (HFD) for \u3e 10 weeks were administered an AAV8-driven vector resulting in constitutive overexpression of mouse Renin1d. HFD-Renin (aka HFpEF ) mice demonstrated obesity and insulin resistance, moderate left ventricular hypertrophy, preserved systolic function, and diastolic dysfunction indicated by echocardiographic measurements; increased left atrial mass; elevated natriuretic peptides; and exercise intolerance. Transcriptomic and metabolomic profiling of HFD-Renin myocardium demonstrated upregulation of pro-fibrotic pathways and downregulation of metabolic pathways, in particular branched chain amino acid catabolism, similar to human HFpEF. Treatment with empagliflozin, an effective but incompletely understood HFpEF therapy, improved multiple endpoints. The HFD-Renin mouse model recapitulates key features of human HFpEF and will enable studies dissecting the contribution of individual pathogenic drivers to this complex syndrome. Additional preclinical HFpEF models allow for orthogonal studies to increase validity in assessment of interventions
Automated Blood Glucose Reminders in the Intraoperative Setting
Full text linkBackground and Review of Literature: Maintaining optimal blood glucose (BG) levels in patients with diabetes (PWD) undergoing surgery is crucial to prevent perioperative complications. Anesthesia providers are expected to adhere to established guidelines for monitoring BG levels in PWD during surgery. However, ensuring consistent adherence to these guidelines remains a challenge.
Purpose: This quality improvement (QI) project aimed to investigate the effect of automated BG reminders on anesthesia provider adherence to an intraoperative BG monitoring guideline for surgical PWD.
Methods: A QI project was conducted at Barnes Jewish Hospital (BJH) over three months. The population of interest was surgical patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
Implementation Plan/Procedure: The automated BG reminder tool was disseminated across the BJC Healthcare Epic system but the Washington University Department of Anesthesia (WUDA) providers’ cases at BJH were the focus of data collection. Adherence to the BG guideline was measured and compared to baseline data. The primary outcome of this project was to assess the impact of automated BG reminders on anesthesia provider adherence to an intraoperative BG guideline. Data analysis included Tableau data using descriptive statistics, Chi-square tests to compare groups, and run charts to quantify differences in guideline adherence frequency pre- and post-real-time reminder implementation. The project aimed to improve patient safety and outcomes by implementing real-time BG reminders to ensure better adherence to an established guideline.
Implications/Conclusions: Findings from this project have the potential to influence practice and enhance the perioperative care of surgical PWD, ultimately leading to improved patient outcomes and healthcare quality
A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests
Full text linkPlasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer\u27s disease pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET and cognition as outcomes and benchmarked them against CSF biomarker tests. Samples from 998 individuals [mean (range) age 68.5 (20.0-92.5) years, 53% female] from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analysed. Plasma p-tau217 was measured with mass spectrometry assays [the ratio between phosphorylated and non-phosphorylated (%p-tau217WashU) and p-tau217WashU] and with immunoassays (p-tau217Lilly, p-tau217Janssen and p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, the US Food and Drug Administration-approved p-tau181/Aβ42Elecsys, and p-tau181Elecsys. All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET [area under the curve (AUC) range: 0.91-0.96] and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff \u3c 0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 0.91 (immunoassays: 0.84-0.87) and a specificity of 0.94 (immunoassays: 0.85-0.89). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (Pdiff \u3c 0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (Pdiff = 0.025). Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared with immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff \u3c 0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff \u3c 0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff \u3c 0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff \u3c 0.014). Among immunoassays, plasma p-tau217Lilly was more associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff \u3c 0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff \u3c 0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination) than all immunoassays (R2: %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; Pdiff \u3c 0.024). The main results were replicated in an external cohort from Washington University in St Louis (n = 219). Finally, p-tau217NULISA showed similar performance to other immunoassays in subsets of both cohorts. In summary, both mass spectrometry- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for Alzheimer\u27s disease pathology, whereas some immunoassays might be better suited as triage tests where positive results are confirmed with a second test, which needs to be determined by future reviews incorporating results from multiple cohorts