Standard Clinical Scores Research Articles

The relationship of clinical presentation, d-dimer levels and previous SARS-CoV-2 positivity in outpatients with suspected pulmonary embolism

Abstract Introduction Elevated D-dimer levels can be detected in patients with pulmonary embolism (PE), but also in patients with the disease caused by the novel coronavirus (COVID-19). Aims To investigate relationship between clinical presentation, D-dimer levels and previous SARS-CoV-2 positivity in outpatients with suspected PE. Material and methods This retrospective study included 609 consecutive outpatients (mean age 68±15 years, 50% female) who underwent computed tomography pulmonary angiography for suspected PE from 2021 to 2023. By reviewing electronic databases, clinical and laboratory data were collected, as well data on previously documented SARS-CoV-2 infection. Results PE was confirmed in 130 (21%) patients who had higher D-dimer values than patients without PE (p<0.001). Patients with previous COVID-19 had significantly higher D-dimer values compared to those without prior COVID-19, but only during the first 8 months from infection to pulmonary angiography (Figure, upper panel). Clinical probability of PE, as indicated by Geneva score [odds ratio (OR) 2.36, 95% confidence interval (CI) 1.55 – 3.58)], and age-adjusted D-dimer (OR 4.52, 95%CI 1.58 – 12.90) were independently associated with PE, while previous COVID-19 was not. Main clinical reasons for emergency department presentation are shown in Figure (bottom panel). In 45/609 (7.4%) patients evaluated primarily for elevated D-dimer, the prevalence of COVID-19 in the previous 6 months was higher in those with PE compared to those without PE (100% vs. 49%, p=0.019). Conclusion Within 8 months of infection, patients with a history of COVID-19 had higher D-dimer levels than those without COVID-19. Age-adjusted D-dimer and standard clinical probability scores retained their predictive power in outpatients with suspected PE, regardless of COVID-19 history.

An automatic measure for speech intelligibility in dysarthrias-validation across multiple languages and neurological disorders.

Dysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework. The study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants' speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed. Verification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability. The ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.

Accelerated MRI reconstructions via variational network and feature domain learning

We introduce three architecture modifications to enhance the performance of the end-to-end (E2E) variational network (VarNet) for undersampled MRI reconstructions. We first implemented the Feature VarNet, which propagates information throughout the cascades of the network in an N-channel feature-space instead of a 2-channel feature-space. Then, we add an attention layer that utilizes the spatial locations of Cartesian undersampling artifacts to further improve performance. Lastly, we combined the Feature and E2E VarNets into the Feature-Image (FI) VarNet, to facilitate cross-domain learning and boost accuracy. Reconstructions were evaluated on the fastMRI dataset using standard metrics and clinical scoring by three neuroradiologists. Feature and FI VarNets outperformed the E2E VarNet for 4×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document}, 5×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} and 8×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} Cartesian undersampling in all studied metrics. FI VarNet secured second place in the public fastMRI leaderboard for 4×\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ imes$$\\end{document} Cartesian undersampling, outperforming all open-source models in the leaderboard. Radiologists rated FI VarNet brain reconstructions with higher quality and sharpness than the E2E VarNet reconstructions. FI VarNet excelled in preserving anatomical details, including blood vessels, whereas E2E VarNet discarded or blurred them in some cases. The proposed FI VarNet enhances the reconstruction quality of undersampled MRI and could enable clinically acceptable reconstructions at higher acceleration factors than currently possible.

Multimodal PA/US imaging in Rheumatoid Arthritis: Enhanced correlation with clinical scores

BackgroundAccurate assessment of Rheumatoid Arthritis (RA) activity remains a challenge. Multimodal photoacoustic/ultrasound (PA/US) joint imaging emerges as a novel imaging modality capable of depicting microvascularization and oxygenation levels in inflamed joints associated with RA. However, the scarcity of large-scale studies limits the exploration of correlating joint oxygenation status with disease activity. ObjectiveThis study aimed to explore the correlation between multimodal PA/US imaging scores and RA disease activity, assessing its clinical applicability in managing RA. MethodsIn this study, we recruited 111 patients diagnosed with RA and conducted examinations of seven small joints on their clinically dominant side using a PA/US imaging system. The PA and power Doppler ultrasound (PDUS) signals were semi-quantitatively assessed using a 0–3 grading system. The cumulative scores for PA and PDUS across these seven joints (PA-sum and PDUS-sum) were calculated. Relative oxygen saturation (So2) values of inflamed joints on the clinically dominant side were measured, and categorized into four distinct PA+So2 patterns. The correlation between PA/US imaging scores and disease activity indices was systematically evaluated. ResultsAnalysis of 777 small joints in 111 patients revealed that the PA-sum scores exhibited a strong positive correlation with standard clinical scores for RA, including DAS28 [ESR] (ρ = 0.682), DAS28 [CRP] (ρ = 0.683), CDAI (ρ = 0.738), and SDAI (ρ = 0.739), all with p < 0.001. These correlations were superior to those of the PDUS-sum scores (DAS28 [ESR] ρ = 0.559, DAS28 [CRP] ρ = 0.555, CDAI ρ = 0.575, SDAI ρ = 0.581, p < 0.001). Significantly, in patients with higher PA-sum scores, notable differences were observed in the erythrocyte sedimentation rate (ESR) (p < 0.01) and swollen joint count 28 (SJC28) (p < 0.01) between hypoxia and intermediate groups. Notably, RA patients in the hypoxia group exhibited higher clinical scores in certain clinical indices. ConclusionMulti-modal PA/US imaging introduces potential advancements in RA assessment, especially regarding So2 evaluations in synovial tissues and associated PA scores. However, further studies are warranted, particularly with more substantial sample sizes and in multi-center settings. SummaryThis study utilized multi-modal PA/US imaging to analyze Rheumatoid Arthritis (RA) patients' synovial tissues and affected joints. When juxtaposed with traditional PDUS imaging, the PA approach demonstrated enhanced sensitivity, especially concerning detecting small vessels in thickened synovium and inflamed tendon sheaths. Furthermore, correlations between the derived PA scores, PA+So2 patterns, and standard clinical RA scores were observed. These findings suggest that multi-modal PA/US imaging could be a valuable tool in the comprehensive assessment of RA, offering insights not only into disease activity but also into the oxygenation status of synovial tissues. However, as promising as these results are, further investigations, especially in larger and diverse patient populations, are imperative. Key points⸸ Multi-modal PA/US Imaging in RA: This novel technique was used to assess the So2 values in synovial tissues and determine PA scores of affected RA joints.⸸ Correlation significantly with Clinical RA Scores: Correlations significantly were noted between PA scores, PA+So2 patterns, and standard clinical RA metrics, hinting at the potential clinical applicability of the technique.

Converting to reverse shoulder arthroplasty from primary anatomic shoulder arthroplasty and fracture hemiarthroplasty: a radiographic and clinical outcome analysis at 8-years.

Revision shoulder arthroplasty can be challenging. One of the main considerations for surgeons is the type of implant that was placed in the initial surgery. Anatomic shoulder arthroplasty (ASA) is used for cases of osteoarthritis as well as for fractures of the humeral head. Hemiarthroplasty can be used for complex proximal humerus fractures. The purpose of this study is to determine whether there is a difference in clinical and radiographic outcomes between patients that failed primary fracture hemiarthroplasty (FHA), or ASA for osteoarthritis and then required reoperation with a conversion to reverse shoulder arthroplasty (RSA). Patients with failed anatomic shoulder replacement, who had undergone conversion to RSA, were enrolled after a mean follow-up of 107 (85-157) months. Two different groups, one with failed ASA implanted for osteoarthritis and one with failed FHA, were created. At follow-up patients were assessed with standard radiographs and clinical outcome scores. Twenty-nine patients (f = 17, m = 12; 51%) suffered from a failed ASA (Group A), while the remaining 28 patients (f = 21, m = 74; 49%) had been revised due to a failed FHA (Group B). Patients of Group B had a poorer Constant score (Group A: 60 vs. Group B: 46; p = 0.02). Abduction (Group A: 115° vs. Group B: 89°; p = 0.02) was worse after conversion of a failed FHA to RSA in comparison to conversions of failed ASA. The mean bone loss of the lateral metaphysis was higher in patients with failed FHA (Group A: 5mm vs. Group B: 20mm; p = 0.0). The initial indication for anatomic shoulder arthroplasty influences the clinical and radiological outcome after conversion to RSA. Conversion of failed FHA to RSA is related to an increased metaphyseal bone loss, decreased range of motion and poorer clinical outcomes when compared to conversions of failed ASA implanted for osteoarthritis. III Retrospective Cohort Comparison Study.

P422 Prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaire in Inflammatory Bowel Disease patients and its association with disease activity and quality of life

Abstract Background An association between active inflammatory bowel disease (IBD) and poor sleep quality has been proposed, however studies evaluating both subjective and objective assessment of disease activity and sleep quality are limited. Our study aimed to investigate the prevalence of poor sleep quality assessed by wrist actigraphy and sleep questionnaires in IBD patients and its association with disease activity and quality of life. Methods A prospective observational study was conducted in Siriraj Hospital, Mahidol University, Bangkok, Thailand from March 2021 to December 2022. Eligible IBD patients were categorized into remission, mild, and moderate-to-severe groups, based on standard clinical disease activity scores. Demographic data, inflammatory markers, inflammatory bowel disease questionnaire (IBDQ), sleep questionnaire (Pittsburgh Sleep Quality Index, PSQI), and seven-day sleep data from wrist actigraphy (Actiwatch®, CamNtech, Cambridge, United Kingdom) were obtained. The prevalence of sleep disorder and group comparison were analyzed. Results Eighty-four participants (40 Crohn’s disease, 44 UC), consisting of 60 remission, 16 mild, and 8 moderate-to-severe disease activity, were enrolled. Baseline demographic data were comparable between each group. Lower hemoglobin and albumin levels, and higher serum C-reactive protein, and fecal calprotectin levels were found in the more clinically active groups (table1). Fifty patients (60%) had poor sleep defined by PSQI &amp;gt; 5 with a trend to be higher in the group with active symptoms (57% in remission, 63% in mild, and 75% in moderate-to-severe group, p=0.31). Using actigraphy, the group with moderate-to-severe symptoms tended to have longer sleep latency, more frequently awake after sleep, and poorer sleep efficiency than the other groups (Figure 1). Patients with more severe disease activity had poorer quality of life with a mean IBDQ of 190 in remission, 159 in mild, and 134 in moderate-to-severe group (p&amp;lt;0.001). Conclusion Poor sleep quality is common among IBD patients, even those with clinical remission. Those with more severe symptoms had poorer sleep quality and worse quality of life. Sleep assessment and treatment should be integrated into IBD standard clinical care.

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis

BACKGROUND & AIMSWe quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis (PSC). METHODSForty-seven patients had baseline testing, and 40 were retested after one year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test) and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT). Disease severity index (DSI), hepatic reserve (HR%), and portal-systemic shunting (SHUNT%) were calculated. RESULTSThree subgroups with low, moderate, and high disease severity were defined from the age-adjusted results for DSI, HR%, and SHUNT%. Standard laboratory tests, clinical scores, cytokine levels, and clinical outcome correlated with these subgroups. In univariate analysis of baseline tests, SHUNT% was a strong predictor of clinical outcome (n=13 of 47; AUROCs 0.84DuO, 0.90SHUNT). A model combining SHUNT%, DSI (or HR%), platelet count, and changes from baseline was most predictive of outcome (n=10 of 40; AUROCs 0.95DuO, 0.96SHUNT). CONCLUSIONDSI, HR%, and SHUNT% identified subgroups of PSC based on the age-related severity of hepatic impairment that predicted risk for liver-related clinical outcome. Further study is warranted to confirm and validate these intriguing findings both in studies of natural progression of PSC and in clinical trials. DuO enhances the utility of quantitative liver function testing.

Regulatory T lymphocytes and selected cytokines in horses with mild to severe equine asthma and different inflammatory cytology profiles

This study determined Tregs and inflammatory cytokines in BALF and peripheral blood (PB) of adult horses with mild and severe asthma and different BALF cytological inflammation profiles. Horses of diverse breeds with asthma (age range: 2–20 years, n = 24) were divided into groups according to the number of points obtained in a standardized clinical scoring system (mild-moderate equine asthma – MEA, severe equine asthma – SEA) and according to the inflammation type based on cytological finding. Plasma levels of IFN-γ, IL-4, IL-10, IL-17 and MMP-9 in the BALF were determined by ELISA. Tregs in the BALF and PB were detected by flow cytometry. Horses with SEA were older than horses with MEA and had higher concentrations of MMP-9 in the BALF (P < 0.05). The neutrophilic inflammation group was characterised by higher age, grade of clinical score, percentage of Tregs and MMP-9 concentration in the BALF compared to the mastocytic inflammation group (P < 0.05). Age positively correlated with neutrophils, grade of score, Tregs in the BALF and in the PB. The grade of score positively correlated with MMP-9. The percentage of Tregs in the BALF positively correlated with Tregs in the PB. Tregs in the BALF and PB positively correlated with neutrophils and MMP-9 in the BALF and with IFN-γ, IL-4 and IL-10 in the plasma. IFN-γ and IL-10 in the plasma positively correlated with the age. The results indicate that the evaluation of selected parameters in PB, the collection of which is less invasive than the collection of BALF, is of potential importance.

Variation in Organizational Clinical Practice Guidelines for Croup.

Croup is one of the most common respiratory complaints in pediatric emergency departments (EDs), yet little is known about clinical practice guidelines (CPGs) for this condition. To describe variation in CPGs across US children's hospitals. We describe the prevalence and features of CPGs among hospitals that submit data to the Pediatric Health Information System. Each hospital was contacted between January 10, 2022, and April 25, 2022, for their most recent croup CPG and any revisions. Characteristics reported were based on the most recent CPG revision. Characteristics included treatment recommendations, utilization measures, ED observation times, and admission criteria. Interrater reliability between reviewers was reported as percentage agreement. Thirty-eight hospitals (79.2%) responded to our query, of which 20 (52.6%) had croup CPGs. Interrater reliability was moderate-high for categorizing the indication for racemic epinephrine (RE) (19 of 20; 95%), the minimum number of RE doses recommended before admission (15 of 20; 75%), and ED observation time (19 of 20; 95%), and was 100% for all other characteristics. Three CPGs (15.0%) recommended 1 RE dose, 14 (70.0%) recommended 2 RE doses, and 3 (15.0%) recommended 3 RE doses before hospital admission. Thirteen (65%) CPGs recommended RE for stridor at rest, whereas 7 (30%) recommended RE for any degree of stridor. Fourteen (70%) CPGs recommended an ED observation time <2 hours, 3 (15%) recommended 2 to 4 hours, and 2 (10%) recommended >4 hours. Few CPGs (15%) recommended use of standardized croup clinical scores. Substantial variation exists among croup CPGs. Our results may inform future efforts to standardize croup CPGs across centers.

Artificial intelligence for dementia-Applied models and digital health.

The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping" cohorts with multi-omics health data become available. This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis, and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors. This review focuses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access; integration of high-throughput biomarker and electronic health record data into modeling; and progressing beyond the primary prediction of dementia to secondary outcomes, for example, treatment response and physical health. Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g., online), or naturalistic (e.g., watch-based accelerometry).

Predictive Modeling Of Alzheimer's Disease Prognosis Using Anatomical & Diffusion MRI.

Mild cognitive impairment (MCI) is an intermediate stage between healthy aging and Alzheimer's disease (AD), and AD is a progressive neurodegenerative disorder that affects around 50 million people worldwide. As new AD treatments begin to be developed, one key goal of AD research is to predict which individuals with MCI are most likely to progress to AD over a given interval (such as 2 years); if successful, these individuals could be preferentially enrolled in drug trials that aim to slow AD progression. Here we benchmarked a range of MCI-to-AD predictive models including linear regressions, support vector machines, and random forests, using predictors from anatomical and diffusion-weighted brain MRI, age, sex, APOE genotype and standardized clinical scores. In evaluations on 2,448 subjects (1,132 MCI, 883 healthy controls, 433 with dementia) from the ADNI study, models including PCA-compacted features achieved a balanced accuracy of 75.3% (using cortical features) and 89.7% using diffusion MRI measures on test set, suggesting the added prognostic value of microstructural metrics obtainable with diffusion MRI.

Based on Tau PET Radiomics Analysis for the Classification of Alzheimer’s Disease and Mild Cognitive Impairment

Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) are closely associated with Tau proteins accumulation. In this study, we aimed to implement radiomics analysis to discover high-order features from pathological biomarker and improve the classification accuracy based on Tau PET images. Two cross-racial independent cohorts from the ADNI database (121 AD patients, 197 MCI patients and 211 normal control (NC) subjects) and Huashan hospital (44 AD patients, 33 MCI patients and 36 NC subjects) were enrolled. The radiomics features of Tau PET imaging of AD related brain regions were computed for classification using a support vector machine (SVM) model. The radiomics model was trained and validated in the ADNI cohort and tested in the Huashan hospital cohort. The standard uptake value ratio (SUVR) and clinical scores model were also performed to compared with radiomics analysis. Additionally, we explored the possibility of using Tau PET radiomics features as a good biomarker to make binary identification of Tau-negative MCI versus Tau-positive MCI or apolipoprotein E (ApoE) ε4 carrier versus ApoE ε4 non-carrier. We found that the radiomics model demonstrated best classification performance in differentiating AD/MCI patients and NC in comparison to SUVR and clinical scores models, with an accuracy of 84.8 ± 4.5%, 73.1 ± 3.6% in the ANDI cohort. Moreover, the radiomics model also demonstrated greater performance in diagnosing AD than other methods in the Huashan hospital cohort, with an accuracy of 81.9 ± 6.1%. In addition, the radiomics model also showed the satisfactory classification performance in the MCI-tau subgroup experiment (72.3 ± 3.5%, 71.9 ± 3.6% and 63.7 ± 5.9%) and in the MCI-ApoE subgroup experiment (73.5 ± 4.3%, 70.1 ± 3.9% and 62.5 ± 5.4%). In conclusion, our study showed that based on Tau PET radiomics analysis has the potential to guide and facilitate clinical diagnosis, further providing evidence for identifying the risk factors in MCI patients.

Differences in CSF Biomarkers Profile of Patients with Parkinson's Disease Treated with MAO-B Inhibitors in Add-On.

Monoamine oxidase type B inhibitors (iMAO-Bs) are a class of largely-used antiparkinsonian agents that, based on experimental evidence, are supposed to exert different degrees of neuroprotection in Parkinson's disease (PD). However, clinical proofs on this regard are very scarce. Since cerebrospinal fluid (CSF) reflects pathological changes occurring at brain level, we examined the neurodegeneration-related CSF biomarkers profile of PD patients under chronic treatment with different iMAO-Bs to identify biochemical signatures suggestive for differential neurobiological effects. Thirty-five PD patients under chronic treatment with different iMAO-Bs in add-on to levodopa were enrolled and grouped in rasagiline (n = 13), selegiline (n = 9), safinamide (n = 13). Respective standard clinical scores for motor and non-motor disturbances, together with CSF biomarkers of neurodegeneration levels (amyloid- β -42, amyloid- β -40, total and 181-phosphorylated tau, and lactate) were collected and compared among the three iMAO-B groups. No significant clinical differences emerged among the iMAO-B groups. CSF levels of tau proteins and lactate were instead different, resulting higher in patients under selegiline than in those under rasagiline and safinamide. Although preliminary and limited, this study indicates that patients under different iMAO-Bs may present distinct profiles of CSF neurodegeneration-related biomarkers, probably because of the differential neurobiological effects of the drugs. Larger studies are now needed to confirm and extend these initial observations.

P-wave beat-to-beat analysis to predict atrial fibrillation recurrence after catheter ablation

Abstract Introduction Identification of patients prone to atrial fibrillation (AF) relapse after catheter ablation is essential for better patient selection and risk stratification. Purpose The current prospective cohort study aims to validate a novel P-wave index based on beat-to-beat (B2B) P-wave morphological and wavelet analysis designed to detect patients with low burden AF, as a predictor of AF recurrence within a year after successful catheter ablation. Methods 12-lead ECG and 10-minute vectorcardiogram (VCG) recordings were obtained from 138 consecutive patients scheduled for AF ablation. Pre-ablation B2B P-wave index, along with standard P-wave indices, clinical scores and patients history and physical examination parameters were evaluated as AF recurrence predictors. Results Univariate analysis revealed that patients with higher B2B P-wave index had a two-fold risk for AF recurrence (HR: 2.35, 95% CI: 1.24–4.44, p: 0.010). Prolonged P-wave, interatrial block, early AF recurrence, female gender, heart failure history, previous stroke, and CHA2DS2-VASc score ≥2 were also found to be related to higher recurrence rate. Multivariate analysis of predictors that can be assessed before ablation revealed that B2B P-wave index, along with heart failure history and history of previous stroke or transient ischemic attack are independent predicting factors of AF relapse. Conclusion B2B P-wave morphology and wavelet analysis, is a promising, non-invasive technique, able to identify patients prone to AF recurrence after pulmonary veins ablation. Further studies are needed to assess the predictive value of B2B index with greater accuracy and evaluate a possible relationship with atrial substrate analysis. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Hellenic Society of Cardiology

Pattern of Mitochondrial Respiration in Peripheral Blood Cells of Patients with Parkinson's Disease.

Mitochondria are central in the pathogenesis of Parkinson’s disease (PD), as they are involved in oxidative stress, synaptopathy, and other immunometabolic pathways. Accordingly, they are emerging as a potential neuroprotection target, although further human-based evidence is needed for therapeutic advancements. This study aims to shape the pattern of mitochondrial respiration in the blood leukocytes of PD patients in relation to both clinical features and the profile of cerebrospinal fluid (CSF) biomarkers of neurodegeneration. Mitochondrial respirometry on the peripheral blood mononucleate cells (PBMCs) of 16 PD patients and 14 controls was conducted using Seahorse Bioscience technology. Bioenergetic parameters were correlated either with standard clinical scores for motor and non-motor disturbances or with CSF levels of α-synuclein, amyloid-β peptides, and tau proteins. In PD, PBMC mitochondrial basal respiration was normal; maximal and spare respiratory capacities were both increased; and ATP production was higher, although not significantly. Maximal and spare respiratory capacity was directly correlated with disease duration, MDS-UPDRS part III and Hoehn and Yahr motor scores; spare respiratory capacity was correlated with the CSF amyloid-β-42 to amyloid-β-42/40 ratio. We provided preliminary evidence showing that mitochondrial respiratory activity increases in the PBMCs of PD patients, probably following the compensatory adaptations to disease progression, in contrast to the bases of the neuropathological substrate.

Initial emergency department vital signs may predict PICU admission in pediatric patients presenting with asthma exacerbation

Objective Severe asthma exacerbations account for a large share of asthma morbidity, mortality, and costs. Here, we aim to identify early predictive factors associated with pediatric intensive care unit (PICU) admission. Methods We performed a retrospective observational study of 5,185 emergency department (ED) encounters at a large children’s hospital, including 86 (1.7%) resulting in PICU admission between 10/1/2015 and 8/7/2018 with ICD9/ICD10 codes for “asthma,” “bronchospasm,” or “wheezing.” Vital signs and demographic information were obtained from electronic health record data and analyzed for each encounter. Predictive factors were identified using adjusted regression models, and our primary outcome was PICU admission. Results Higher mean heart rates (HRs) and respiratory rates (RRs), and lower SpO2 within the first hour of ED presentation were independently associated with PICU admission. Odds of PICU admission increased 70% for each 10 beats/min higher HR, 125% for each 10 breaths/min higher RR, and 34% for each 5% lower SpO2. A binary predictive index using 1-h vitals yielded OR 13.4 (95% CI 8.1–22.1) for PICU admission, area under receiver operator characteristic (AUROC) curve 0.84 and overall accuracy of 80.1%. Results were largely unchanged (AUROC 0.84–0.88) after adjusting for surrogates of asthma severity and initial ED management. In combination with a secondary standardized clinical asthma distress score, positive predictive value increased by sevenfold (6.1%–46%). Conclusions A predictive index using HR, RR, and SpO2 within the first hour of ED presentation accurately predicted PICU admission in this cohort. Automated vital signs trend analysis may help identify vulnerable patients quickly upon presentation.

B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases

BackgroundIn the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35–55). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases.MethodsThe present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing.ResultsWe observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evidenced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected.ConclusionTherefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments.

NLRP3 in the Cerebrospinal Fluid as a Potential Biomarker for the Diagnosis and Prognosis of Community-Acquired Bacterial Meningitis in Adults.

ObjectiveTo discover the levels of NLR family pyrin domain-containing 3 (NLRP3) in the cerebrospinal fluid (CSF) from adult patients with community-acquired bacterial meningitis (CABM).MethodsWe enrolled 34 patients with CABM, 20 patients with viral meningitis (VM), and 25 patients with non-inflammatory neurological disease. Data on standard clinical parameters, scores, and outcomes were obtained from clinical records, and inflammasome levels in the CSF were measured by an enzyme-linked immunosorbent assay. The area under the receiver operating characteristic curve (AUROC) was used to quantify the diagnostic and prognostic performance of CSF NLRP3 as a biomarker of CABM.ResultsThe levels of NLRP3 were elevated in the CSF of patients with CABM, but levels for ASC, caspase-1, or other inflammasomes did not vary significantly. CSF NLRP3 was positively correlated with clinical severity and with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte count, albumin quotient (Qalb), and immunoglobulin G quotient (QIgG). Patients with unfavorable outcomes had higher levels of NLRP3 in the CSF, which were correlated with several blood indicators, including NLR, PLR, and lymphocyte and monocyte counts.ConclusionsOur results suggested that the level of CSF NLRP3 could represent the severity of CABM in adults. CSF NLRP3 may be a good biomarker for the diagnosis of CABM and for the discrimination between CABM and VM. It may also be a better biomarker for predicting the prognosis of adult patients with CABM when compared to the NLR or the lymphocyte and monocyte counts.

Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition

Alpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinson’s disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration- (CCR2, CD11b) and phagocytic- (CD163) markers, particularly on classical and intermediate monocytes in early Parkinson’s disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinson’s Disease. The disease-associated immune changes of CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinson’s disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both symptoms and the sex bias of the disease.