Measures Of Disease Severity Research Articles

Bilateral leg stepping coherence as a predictor of freezing of gait in patients with Parkinson's Disease walking with wearable sensors.

Fourteen participants with PD (in OFF state) were asked to walk in challenging conditions (e.g. with turning, dual-task walking, etc.) while wearing inertial motion sensors (waist, 2 shanks) and being videotaped. Occasionally, participants were asked to voluntarily stop (VOL). FOG and VOL events were identified by trained researchers based on videos. Wavelet analysis was performed on shank sagittal velocity signals and a synchronization loss threshold (SLT) was defined and compared between FOG and VOL. A proof-of-concept analysis was performed for a subset of the data to obtain preliminary classification characteristics of the novel measure. 128 FOG and 42 VOL episodes were analyzed. SLT occurred earlier for FOG (MED=1.81 sec prior to stop, IQR=1.57) than for VOL events (MED=0.22 sec, IQR=0.76) (Z=-4.3, p<0.001, ES=1.15). These time differences were not related with measures of disease severity. Preliminary results demonstrate sensitivity of 98%, specificity of 42% (mostly due to 'turns' detection) and balanced accuracy of 70% for SLT-based prediction, with good differentiation between FOG and VOL. Wavelet analysis provides a relatively simple, promising approach for prediction of FOG in people with PD.

Decreased Cardiac Autonomic Function is Associated with Higher Exacerbation Risk and Symptom Burden in Chronic Obstructive Pulmonary Disease.

Current measures of chronic obstructive pulmonary disease (COPD) severity, including lung function, do not fully explain symptom burden, and there is a need to identify predictors of exacerbation risk and morbidity. Autonomic dysfunction may be implicated in both cardiovascular and respiratory morbidity in COPD and convey risk for exacerbations. Heart rate variability (HRV) is a marker of cardiac autonomic function that is predictive of cardiovascular health and has promise as a non-invasive COPD biomarker. The CLEAN AIR Heart study provided an opportunity to investigate the association between HRV and COPD morbidity among former smokers with moderate-severe COPD. Eighty-five participants, contributing 305 HRV measurements, underwent repeated clinical assessments over 4 study periods that included a 24-Holter monitoring assessment of HRV. HRV measures of interest were standard deviation of normal-to-normal intervals, (SDNN) (overall HRV) and root-mean-square of successive differences (RMSSD) (parasympathetic function). Exacerbation risk was assessed using negative binomial models, and mixed-effects models analyzed associations between HRV and symptoms. Decreases in SDNN (incidence rate ratio [IRR]1.40; 95% confidence interval [CI] 1.13 to1.74) and RMSSD (IRR 1.60; 95% CI 1.07 to 2.37) were associated with severe exacerbation risk. Decreases in SDNN were associated with higher St George's Respiratory Questionnaire scores, COPD Assessment Test scores, and chronic bronchitis symptoms. Findings demonstrate that HRV is associated with COPD symptom burden and exacerbation risk. HRV may represent an important biomarker with the potential to identify high-risk COPD populations.

Associations of Combustible Cigarette, Electronic Cigarette, and Dual Use With COVID Infection and Severity in the U.S.: A Cross-sectional Analysis of the 2021 National Health Information Survey.

Given the potential respiratory health risks, the association of COVID infection and the use of combustible cigarettes, electronic nicotine delivery systems (ENDS), and concurrent dual use is a priority for public health. Many published reports have not accounted for known covarying factors. This study sought to calculate adjusted odds ratios for self-reported COVID infection and disease severity as a function of smoking and ENDS use, while accounting for factors known to influence COVID infection and disease severity (i.e., age, sex, race and ethnicity, socioeconomic status and educational attainment, rural or urban environment, self-reported diabetes, COPD, coronary heart disease, and obesity status). Data from the 2021 U.S. National Health Interview Survey, a cross-sectional questionnaire design, were used to calculate both unadjusted and adjusted odds ratios for self-reported COVID infection and severity of symptoms. Results indicate that combustible cigarette use is associated with a lower likelihood of self-reported COVID infection relative to non-use of tobacco products (AOR = .64; 95% CI [.55, .74]), whereas ENDS use is associated with a higher likelihood of self-reported COVID infection (AOR = 1.30; 95% CI [1.04, 1.63]). There was no significant difference in COVID infection among dual users (ENDS and combustible use) when compared with non-users. Adjusting for covarying factors did not substantially change the results. There were no significant differences in COVID disease severity between those of varying smoking status. Future research should examine the relationship between smoking status and COVID infection and disease severity utilizing longitudinal study designs and non-self-report measures of smoking status (e.g., the biomarker cotinine), COVID infection (e.g., positive tests), and disease severity (e.g., hospitalizations, ventilator assistance, mortality, and ongoing symptoms of long COVID).

An image-based technique for automated root disease severity assessment using PlantCV.

Plant disease severity assessments are used to quantify plant-pathogen interactions and identify disease-resistant lines. One common method for disease assessment involves scoring tissue manually using a semi-quantitative scale. Automating assessments would provide fast, unbiased, and quantitative measurements of root disease severity, allowing for improved consistency within and across large data sets. However, using traditional Root System Markup Language (RSML) software in the study of root responses to pathogens presents additional challenges; these include the removal of necrotic tissue during the thresholding process, which results in inaccurate image analysis. Using PlantCV, we developed a Python-based pipeline, herein called RootDS, with two main objectives: (1) improving disease severity phenotyping and (2) generating binary images as inputs for RSML software. We tested the pipeline in common bean inoculated with Fusarium root rot. Quantitative disease scores and root area generated by this pipeline had a strong correlation with manually curated values (R 2 = 0.92 and 0.90, respectively) and provided a broader capture of variation than manual disease scores. Compared to traditional manual thresholding, images generated using our pipeline did not affect RSML output. Overall, the RootDS pipeline provides greater functionality in disease score data sets and provides an alternative method for generating image sets for use in available RSML software.

Serum Galectin-3 in Hepatitis C Virus Infection Declines after Successful Virus Eradication by Direct-Acting Antiviral Therapy

Serum galectin-3 is regarded as an inflammatory marker in patients with chronic liver diseases. Hepatitis C virus (HCV) infection is associated with higher levels of inflammatory molecules which ameliorate by efficient treatment with direct-acting antivirals (DAAs). The aim of this study was to compare serum galectin-3 levels between HCV patients before treatment with DAAs and at the time of sustained virologic response at 12 weeks post-treatment (SVR12). Hepatitis B and human immunodeficiency virus-negative HCV infected patients not treated with HCV therapies before were recruited at the University Hospital of Regensburg. Galectin-3 was measured by enzyme-linked immunosorbent assay in the serum of patients with chronic HCV infection, before treatment initializing, at four and twelve weeks after the start of DAA therapy and at SVR12. Associations of serum galectin-3 with C-reactive protein (CRP), leukocyte count and measures of liver disease severity were analyzed. Liver fibrosis was assessed by acoustic radiation force impulse, the aspartate aminotransferase/platelet ratio index, and the fibrosis-4 score. In the serum of 81 HCV patients, galectin-3 did not correlate with viral load, viral genotype, CRP, leukocyte count, or the model for end stage liver disease score. Therapy with DAAs effectively diminished viral load within four weeks in all patients. The median value of the serum galectin-3 was 3.0 (Q1:2.0, Q3:4.0) ng/ml before therapy and declined to 2.4 (Q1: 1.7, Q3: 3.4) ng/ml at SVR12 (p<0.001; paired samples of 67 patients). At SVR12, serum galectin-3 was not correlated with CRP (r=0.057, p=0.646) or leu-kocyte count (r=0.222, p=0.071) and did not change with increasing fibrosis stage. The associations between serum galectin-3 and body mass index, liver steatosis or diabetes could not be observed. Elimination of HCV by DAA treatment lowered serum galectin-3 compared to the pre-treatment levels suggesting that HCV infection causes an increase of this immune-regulatory protein.

247. Catching CAPA: The Healthcare Impact of COVID-19-Associated Pulmonary Aspergillosis in an Academic Medical Center

Abstract Background COVID-19 associated pulmonary aspergillosis (CAPA) is a known complication of COVID-19 which carries a high mortality rate. While there are proposed diagnostic criteria, CAPA remains likely underdiagnosed. Our objectives are to evaluate markers of disease severity, bacterial coinfections, and outcome measures in order to assess the clinical impact of CAPA in patients admitted with COVID-19. Methods A retrospective chart review was performed on all adult patients admitted to a single-center, tertiary hospital from March 1, 2020 to May 1, 2022 with a positive COVID-19 PCR and probable or proven CAPA based on ECMM/ISHAM consensus criteria. Admission data, ICU status, time to CAPA diagnosis, respiratory cultures, and 90-day mortality were identified. Results 14 patients met criteria for probable CAPA. 10 of 14 patients (71.4%) were immediately admitted to the ICU. By day 14, 13 patients (92.9%) were intubated. The average time from admission to CAPA diagnosis was 31.3 days. 12 patients were diagnosed by BAL galactomannan, while 2 patients were diagnosed by growth on respiratory culture. 12 patients (85.7%) also had bacterial growth on respiratory cultures. The most common pathogen was Staphylococcus aureus, which was seen in 6 patients. All-cause mortality was 42.8%, or 6 of 14 patients, at day 90. In patients with a CAPA diagnosis, the average length of ICU stay was 36.4 days and average total hospital length of stay was 43.6 days, compared to 6.3 and 12.5 days, respectively, for all patients admitted with COVID-19 disease. Conclusion CAPA is a rare complication of COVID-19 but had substantial negative impacts on affected patients. The late onset of CAPA may be a result from longer hospitalizations and increased healthcare-associated infections. The association of CAPA with bacterial coinfections is consistent with literature on other viral infections such as influenza predisposing to secondary pneumonias. As the majority of cases were diagnosed by galactomannan rather than culture, providers should have a low threshold for testing in patients with protracted hospitalization for COVID-19. This case series emphasizes the poor outcomes associated with CAPA and its burden on already strained hospital resources, highlighting the need for improved disease awareness and further study. Disclosures All Authors: No reported disclosures.

Effectiveness of Guselkumab Therapy among Patients with Plaque Psoriasis with Baseline IGA Score ≥ 2 in the CorEvitas Psoriasis Registry.

In clinical trials, treatment with the interleukin-23 inhibitor guselkumab was associated with significantly improved disease severity and patient-reported outcome measures (PROMs) among patients with moderate-to-severe plaque psoriasis. However, limited information is available regarding the real-world effectiveness of guselkumab among patients with psoriasis of mild, moderate, and severe Investigator's Global Assessment (IGA) severities living in the USA and Canada. Patients participating in the CorEvitas Psoriasis Registry between 18 July 2017 and 10 July 2019 who met the following criteria were included: IGA ≥ 2 (mild or greater disease severity), initiated guselkumab at a registry (index) visit, and had a registry follow-up visit after persistent guselkumab treatment for 9 to 12months. Data were collected for patient demographics, disease characteristics, treatment history, disease activity, and PROMs. At follow-up, outcome measure response rates and mean changes from the index visit were calculated. Among 130 patients, the mean age was 50.2years, 39.2% were female, and 56.9% had a body mass index ≥ 30kg/m2. Mean psoriasis duration was 17.5years and 79.2% of patients had previously received one or more biologic therapy. At the index visit, mean IGA, Psoriasis Area Severity Index (PASI), and Dermatology Life Quality Index (DLQI) scores were 3.0, 9.9, and 8.0, respectively. At follow-up, IGA0/1 and IGA 0 were achieved by 64.6% and 36.2% of patients, respectively. PASI75, 90, and 100 were achieved by 61.5%, 46.9%, and 36.9% of patients; 55.4% had maintained or achieved DLQI0/1. Mean improvements were observed in all evaluated disease activity outcomes and PROMs, with all differing significantly from zero except for the percent of work hours missed due to psoriasis. In this real-world study, patients with a baseline IGA score ≥ 2 experienced improvements in disease activity and PROMs after 9-12months of persistent guselkumab treatment.

Costs of dementia in Europe: a systematic literature review and meta‐analysis

AbstractBackgroundReliable data on costs of dementia care is critically important for estimating the value of novel therapies, technologies and methods in dementia care. The costs of dementia have been described in an increasing number of studies, however many are limited by small, selected samples and incomplete scope of cost categories included. Comparison of results has been challenged by considerable methodological heterogeneity, however increasing standardization of how resource utilization is measured and valued is increasing opportunities for systematic compilation of results. In this study we summarize available evidence on the costs of dementia in Europe through meta‐analysis on individual cost items.MethodWe conducted a systematic literature review to identify studies that collect and report costs of care in individuals with dementia. Costs were assessed in seven categories covering direct medical care (inpatient care, outpatient care, drugs), direct non‐medical care (institutional care, home care) and informal care (caregiver time loss, caregiver work loss). Data on study methodology, patient populations, care setting and disease severity was abstracted and harmonized across studies, and costs were converted to 2021 EUR.Result115 studies were included in the final review and meta‐analysis, reporting data for 631,281 patients from 17 countries. Annual total costs vary between regions within Europe, from approximately €6,000 EUR in Eastern Europe to €50,000 in Northern Europe, but consistently increase with disease severity and for institutionalized patients. Costs are dominated by informal care and non‐medical direct costs, while the balance of these two vary between regions. About half of the studies used a standardized scale for collecting resource utilization and cost data, the most common of which was the Resource Use in Dementia (RUD) instrument.ConclusionIn this study we construct the most comprehensive database to date of costs of dementia in relation to disease severity and care setting. Meta‐analytical estimates of care costs are possible but require categorization of resource use items and cross‐mapping of different measures of disease severity.

PTau heterogeneity as a measure for disease severity in incipient Alzheimer's disease

AbstractBackgroundThe presence of p‐tau in biofluids has previously been proposed to be a response to neurofibrillary tangle pathology, one of the hallmarks of Alzheimer’s disease (AD). However, the increase of p‐tau in cerebrospinal fluid (CSF) precedes detectable neurofibrillary tangle pathology, as indexed by tau Positron Emission Tomography (PET), by up to a decade, suggesting that soluble tau could be an indication of early tau pathology. With this study, we investigated the heterogeneity of p‐tau species in CSF to assess the disease status of participants of the Translational Biomarkers of Aging and Dementia (TRIAD) cohort.MethodsSupport vector machines were used to determine cutoff values of p‐tau181, p‐tau217, p‐tau231 and p‐tau235 in CSF, identifying a group of participants that were amyloid positive (58 from a total of 165 participants). Amyloid positivity was determined by using an [18F]AZD4694 SUVR threshold value of 1.55 in the neocortex. Using these cutoff values, signatures were calculated on an individual level to identify the number of phosphorylated sites. Based on the number of phosphorylated sites, [18F]MK6240 SUVR maps and [18F]AZD4694 SUVR maps were calculated.ResultsWhen combining different CSF p‐tau species, the largest contribution in identifying amyloid positivity came from p‐tau217, followed by p‐tau231, p‐tau181 and p‐tau235. Achieving the cutoff for multiple p‐tau species was associated with more tau pathology particularly in the later Braak stages (fig 1) and increased amyloid‐β plaque accumulation (fig 2).ConclusionOur findings suggest that heterogeneity in p‐tau species carries predictive power in the identification of disease severity in incipient Alzheimer’s Disease.

The Neurofilament Surveillance Project (NSP): A biomarker study to sample blood quarterly in familial frontotemporal lobar degeneration

AbstractBackgroundIn familial frontotemporal lobar degeneration (f‐FTLD), plasma levels of neurofilament light (NfL) are elevated at least two years prior to symptom onset and predict future clinical status. The Neurofilament Surveillance Project (NSP), an actively recruiting observational study, seeks to obtain higher resolution data of temporal changes in plasma NfL to better understand its clinical utility in f‐FTLD interventional trials. The NSP is a pre‐competitive collaboration sponsored by the Bluefield Project to Cure FTD and funded by biotechnology and pharmaceutical companies and nonprofit organizations.MethodParticipants must be members of families with disease‐causing mutations in C9orf72, MAPT or GRN and enrolled in the ALLFTD natural history study. Up to 335 participants, with roughly equal representation across mutation type, provide plasma quarterly for 3 years (4355 samples total) to enable the observation of peripheral NfL levels longitudinally during disease onset and progression. Plasma is collected by certified mobile research nurses during remote visits, and NfL is measured in batch at least every 6 months. NfL measurements from one plasma aliquot per draw will be correlated with annual assessments obtained in the ALLFTD study, including measures of disease severity (CDRÒ+NACC‐FTLD, CGI, etc.), cognitive function from the UDS Neuropsychology Battery, and volumetric MRI data. Additional plasma aliquots are reserved for future analyses of other biomarkers during the course of the study; another subset of aliquots is reserved to share with interested investigators after the study ends.ResultAs of 1/19/22, the NSP had enrolled 161 participants, including 62 from C9orf72 kindreds, 60 from MAPT kindreds, and 28 from GRN kindreds. One‐hundred forty‐five participants had completed their initial visit, and 109 had completed more than 3, and up to 5, quarterly blood draws. Enrollment and study visits are ongoing despite COVID‐related limitations.ConclusionThe quarterly blood sampling from this study, combined with annual comprehensive clinical assessments through the ALLFTD natural history study, will enable a more detailed understanding of when and how NfL levels change during phenoconversion and/or disease progression in f‐FTLD mutation carriers. These data will be especially informative in the context of the targeted investigational therapeutics for f‐FTLD now entering clinical trials.

Somatoform Symptoms in Parkinson Disease.

Co-occurring somatoform symptoms complicate the diagnosis and treatment of Parkinson disease (PD). To learn more about the relationship between somatoform symptoms and PD by comparing demographic and clinical features across PD groups differing in somatoform symptom severity. Using standardized Brief Symptom Inventory-18 (BSI-18) scores to measure somatoform symptom severity, we assigned 1093 individuals with PD to one of four subgroups using comparisons to normative means: low (M < -½ SD), average (M ± ½ SD), high (M +½ SD to +1 SD), very high (M > +1 SD). We used demographics and disease severity measures to assess each subgroup. Most of the individuals with PD (56%) had high or very high somatoform symptom levels. Increased somatoform symptom levels were associated with female gender, lower socioeconomic status, greater disease duration, increased PD severity (Total Unified Parkinson's Disease Rating Scale), greater disability (Older Americans Resource and Services Disability subscale), increased BSI-18 Depression and Anxiety subscale scores, lower cognitive function (Mini-Mental State Examination), lower self-efficacy scores (Self-Efficacy to Manage Chronic Disease Scale), lower quality of life scores (SF-12 Health Status Survey), and greater medical comorbidity (Cumulative Illness Rating Scale-Geriatrics) (all comparisons: P < 0.001). We found no significant between-group differences for age, race, or marital status. Somatoform symptom severity in individuals with PD is associated with greater PD severity and disability and is more common in females and in individuals with low socioeconomic status. Greater awareness of somatoform symptoms should help improve PD treatment.

Biomarker modelling of Alzheimer's disease using in vivo Braak staging

AbstractBackgroundGold standard diagnostic methods for AD rely on staging systems to measure disease severity, which have not yet been incorporated into the in vivo biological research framework for AD. The topographical information conferred by tau‐PET offers the potential to translate the gold standard histopathological Braak staging system to living individuals.MethodUsing the topographical information from [18F]MK6240 tau‐PET, we applied the Braak tau staging system to 324 living individuals. We used PET‐based Braak stage to model the trajectories of amyloid‐b, phosphorylated tau in cerebrospinal fluid (pTau181, pTau217, pTau231, pTau235) and plasma (pTau181, pTau231), neurodegeneration and cognitive symptoms.ResultPET‐based Braak stages were We identified nonlinear AD biomarker trajectories corresponding to the spatial extent of tau‐PET, with modest biomarker changes detectable by Braak stage II and significant changes occurring at stages III‐IV, followed by plateaus. Early Braak stages were associated with isolated memory impairment, while Braak stages V‐VI were incompatible with normal cognition. Follow up tau‐PET scans indicated sequential progression of in vivo Braak stages over time, with progression beyond Braak stage III requiring the presence of amyloid‐beta abnormality.ConclusionOur results support PET‐based Braak staging as a framework to model the natural history of AD, as well as monitor AD severity from presymptomatic to clinical dementia phases.

Evaluation of Skindex-16 construct validity in routinely collected psoriasis data: a retrospective analysis of the relationship between overall physician global assessment scores and Skindex-16 and measure discordance.

Patient-reported outcome measures (PROMs) capture disease severity metrics from the patient's perspective, including health-related quality of life (HRQL). Disease-specific validation of PROMs improves their clinical utility. We evaluated construct validity (HRQL) for Skindex-16 in routinely seen psoriasis patients and characterized instances of discordance between Skindex-16 scores and clinician-reported outcome measure of disease severity. We retrospectively studied psoriasis patients seen by University of Utah Dermatology from 2016 to 2020. Cross-sectional construct validity was assessed using quantile regression and Spearman correlation between overall physician global assessment (OPGA) score and Skindex-16 scores. Longitudinal within-subject correlation was performed using linear mixed models. Discordance (10th percentile or lower OPGA and 90th percentile or higher Skindex-16 score [clear skin, poor HRQL; cspHRQL] or the reverse [severe skin, good HRQL; ssgHRQL]) was characterized descriptively. 681 first-visit patients with psoriasis were included. Median overall Skindex-16 score varied by ≥ 10 points across all levels of OPGA scores. OPGA and Skindex-16 domain scores were moderately correlated (emotions ρ = 0.54, functioning ρ = 0.47, and symptoms ρ = 53). Longitudinal correlations were similar (emotion ρxy = 0.54, functioning ρxy = 0.65, symptoms ρxy = 0.47). Visits with cspHRQL discordance occurred for each Skindex-16 domain (emotions = 7, functioning = 13, symptoms = 12). The ssgHRQL group was observed within the emotions (n = 1) and functioning (n = 23) domains. Median Skindex-16 scores are different between different levels of OPGA and show moderate cross-sectional and longitudinal correlation. This supports construct validity in patients with psoriasis. Severe discordance was rare and most often for those with clear skin but poor HRQL. These discordances can prompt further patient-clinician conversation.

Organ Donation and Transplants During Major US Motorcycle Rallies

Large-scale motorcycle rallies attract thousands of attendees and are associated with increased trauma-related morbidity and mortality. To examine the association of major US motorcycle rallies with the incidence of organ donation and transplants. This population-based, retrospective cross-sectional study used data from the Scientific Registry of Transplant Recipients for deceased organ donors aged 16 years or older involved in a motor vehicle crash and recipients of organs from these donors from March 2005 to September 2021. Dates of 7 large US motorcycle rallies and regions near these events. The main outcomes were incidence of motor vehicle crash-related organ donation and number of patients receiving a solid organ transplant from these donors. An event study design was used to estimate adjusted rates of organ donation during the dates of 7 major US motorcycle rallies compared with the 4 weeks before and after the rallies in rally-affected and rally-unaffected (control) regions. Donor and recipient characteristics and metrics of organ quality were compared between rally and nonrally dates. The study included 10 798 organ donors (70.9% male; mean [SD] age, 32.5 [13.7] years) and 35 329 recipients of these organs (64.0% male; 49.3 [15.5] years). During the rally dates, there were 406 organ donors and 1400 transplant recipients. During the 4 weeks before and after the rallies, there were 2332 organ donors and 7714 transplant recipients. Donors and recipients during rally and nonrally dates were similar in demographic and clinical characteristics, measures of organ quality, measures of recipient disease severity, and recipient waiting time. During rallies, there were 21% more organ donors per day (incidence rate ratio [IRR], 1.21; 95% CI, 1.09-1.35; P = .001) and 26% more transplant recipients per day (IRR, 1.26; 95% CI, 1.12-1.42; P < .001) compared with the 4 weeks before and after the rallies in the regions where they were held. In this cross-sectional study, major motorcycle rallies in the US were associated with increased incidence of organ donation and transplants. While safety measures to minimize morbidity and mortality during motorcycle rallies should be prioritized, this study showed the downstream association of these events with organ donation and transplants.

Correlation between whole body muscle MRI and functional measures in paediatric patients with facioscapulohumeral muscular dystrophy

Symptoms and severity of facioscapulohumeral muscular dystrophy (FSHD) can vary greatly, even within the same family. Clinical trial readiness requires accurate and reliable methods of assessing disease stage and progression. MRI has not previously been assessed as a disease biomarker in paediatric FSHD. Eleven patients with FSHD1 underwent whole body muscle MRI. Pre-selected muscles were analysed by a paediatric radiologist using the semi-quantitative Mercuri/Kim method. Within each domain (oedema, fat replacement, atrophy) scores for each muscle were then summated to give each participant three cumulative domain scores. The same participants had functional measures scored: FSHD-CSS (Ricci), FSHD-CS (Lamperti), FSHD-COM, PUL2.0, MFM-32, 6MWT, myometry and manual muscle testing. Pearson coefficient was calculated to determine strength of correlation. The scores for atrophy and fat replacement showed strong correlation with functional outcome measures, particularly FSHD-CSS, FSHD-CS and FSHD-COM. In contrast, muscle oedema correlated poorly with all functional outcome measures, with no relationship seen to the 6MWT. This study of eleven children suggests that semi-quantitative visual Mercuri score utilising fat replacement or atrophy on whole body muscle MRI correlates strongly with disease-specific functional measures and may be a useful measure of disease severity in paediatric FSHD.

409 EASI p-EASI: predicting disease severity in atopic dermatitis patients treated with tralokinumab

Numerous targeted treatments for atopic dermatitis (AD) are currently under investigation in clinical trials. Comparability of the efficacy of new drugs is therefore becoming more important. Serum biomarkers may offer an objective outcome measure for disease severity in AD. A combination of serum biomarkers TARC, IL-22, and sIL-2R as a signature (predicted EASI) may offer an objective measurement tool for disease severity in AD patients treated with topical steroids, cyclosporin A, or dupilumab.

Blood Neutrophil Count and Neutrophil-to-Lymphocyte Ratio for Prediction of Disease Progression and Mortality in Two Independent Systemic Sclerosis Cohorts.

To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc). Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b= -4.74, P=0.009 and b=-2.68, P=0.028, respectively) and higher serially obtained MRSS (b=4.07, P < 0.001 and b=2.32, P < 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P=0.02 and HR 1.48, P < 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II. Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc.

A SINGLE-CENTRE RETROSPECTIVE AND OBSERVATIONAL INVESTIGATION ON THE MANIFESTATIONS OF COVID-19 ON CHEST HRCT IN THEPOPULATION OF ANDHRA PRADESH, INDIA

Background: The clinical symptoms of COVID-19 in conjunction with chest high resolution computed tomography (HRCT) can give quick screening and determine the disease's severity. HRCT plays an important role in the evaluation and clinical management of COVID-19, which would benet from a more comprehensive overview of its clinical diagnosis and therapy. To dene the spectrum of HRCT results in Objective: COVID 19 individuals with symptoms and to connect HRCT ndings with clinical symptoms of the disease. A retrospective r Methods: esearch of 1513 COVID patients recently diagnosed with COVID-19 and positive RT-PCR test ndings; both sexes were included from the middle of March to the end of May 2021. The patients were separated into three age groups and their HRCT CT severity scores (CTSS) were evaluated. Different age groups' clinical symptoms were connected with the derived CTSS. Results: The average age of the patients was 50.14 percent, with 34% falling between the ages of 35 and 54. The majority of them had fever, cough, dyspnea, myalgia, and headache, but other symptoms like sore throat, diarrhoea, nausea, anosmia, and chest discomfort were less common. In the current study, clinical characteristics had the strongest relationship with moderate CTSS. HRCT ndings include ground-glass opacity (GGO), consolidation, bronchovascular thickening, crazy paving look, subpleural bands/brosis, and bronchiectasis. In moderate and severe patient groups, the CTSS link with lung lobe distribution and gender was highly signicant. Bilateral lung distribution changes (83.6%) were more common in group 2 than central and peripheral distribution changes (70.5%), with lower lobe involvement in both genders. Conclusion: HRCT helps identify COVID-19's pulmonary symptoms in diagnosis and treatment. Imaging patterns depending on infection duration help understand pathophysiology and predict illness development and effects. This study may link clinical symptoms to CTSS and COVID-19 pulmonary changes. It could mean understanding the following wave's features and management. HRCT chest detects early parenchymal abnormalities, measures disease severity in all symptomatic patients, and diagnoses COVID infection regardless of RT-PCR status.

Presence of Activating STAT3 Mutations in the CD8+ T Cells of Rheumatoid Arthritis Patients

Rheumatoid Arthritis (RA) is a systemic autoimmune disorder afflicting around 1% of the global population. It is treated with a variety of immunosuppressants typically progressing from first line therapies such as low dose methotrexate (MTX) or other disease modifying anti-rheumatic drugs (DMARDs) to second line treatments such as tumor necrosis factor (TNF) inhibitors or other biologics designed to target pro-inflammatory cytokines. Several factors are used to anticipate and measure disease severity including Disease Activity Measures (DAM) and positivity of rheumatoid factor (RF), antibodies to cyclic citrullinated protein (CCP), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Presence of anti-CCP antibody is the most specific of these markers of RA, and its presence may be associated with more severe disease. Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy characterized by clonal proliferation of natural killer or CD8+ T cells, somatic activating mutations in the signaling transducer and activator of transcription 3 (STAT3) gene, and clinical features including neutropenia and anemia. Interestingly, LGL leukemia is strongly associated with RA, with as high as 36% of patients exhibiting concomitant RA. There is significant overlap between the diseases. Both RA alone and in combination with LGL leukemia exhibit cytotoxic T cell expansions, HLA-DR4 enrichment, female bias, and RA-associated autoantibodies. The dominant molecular hallmark of LGL leukemia is somatic activating STAT3 mutation. Most patients exhibit increased activation of STAT3 through phosphorylation, and 50% or more patients have a mutation in STAT3, the most common being missense mutations, Y640F and D661Y. Of note, LGL leukemia patients with one or more STAT3 mutations are more likely to suffer from concomitant RA. Based on these observations, we hypothesized that STAT3 mutations would be enriched in RA patients compared to the general population and that the presence of mutations may correlate with specific clinical characteristics of RA. In this study, blood samples and demographic data were simultaneously collected from 96 RA patients at the UVA Rheumatology Clinic. CD8+ cells were isolated from blood samples and DNA was extracted and analyzed via droplet digital PCR to detect Y640F, D661Y, and S614R_G618R STAT3 mutations. Figure A shows that roughly 3% (3/96) of the RA samples had a STAT3 mutation in greater than 5% of the DNA analyzed. Additionally, an even larger proportion of RA patients had either Y640F or D661Y mutations at a rate of between 1:100 and 1:1000 cells (10/96 Y640F, 14/96 D661Y). These samples were classified as mutated for the purposes of statistical analysis. Of the 9 healthy control samples analyzed, only one exhibited a mutation of this size (1/9 Y640F, 0/9 D661Y). Correlation with clinical parameters showed similar disease manifestations between WT and STAT3 mutant samples. However, CCP differed between mutational types, with the Y640F group exhibiting higher positivity than the D661Y group (Figure B). Taken together, the increased presence of STAT3 activating mutations in CD8+ cells isolated from RA blood samples as well as the difference in CCP positivity between D661Y and Y640F mutational groups merits further investigation of these pathways in RA. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Pilot Trial of Dopamine Replacement for Dynamic Facial Expressions in Parkinson's Disease.

Current conflict exists regarding the potential beneficial effects of dopamine medications on facial expressivity in Parkinson's disease. Via digital video analysis software, we previously found reduced facial movement (entropy) and slower time to reach peak entropy in individuals with Parkinson's disease compared to controls. We aimed to determine whether levodopa medications improved parameters of dynamic facial expressions (amplitude, speed). A total of 34 individuals with idiopathic Parkinson's disease were videotaped making voluntary facial expressions (happy, fear, anger, disgust) when "on" and "off" levodopa. Participants were 52 to 80 years old, early to mid-stage disease, non-demented, and included more men (65%). Expressions were digitized and analyzed using software that extracted three variables: two indices of movement change (total entropy, percent entropy change) and time to reach peak expression. Indices of facial movement (total entropy, peak entropy) and timing were significantly improved when patients were "on" vs "off" medication (all F's ≥ 3.00, P < 0.05). For total movement and time to reach peak entropy, levodopa-related improvements were emotion nonspecific. Levodopa-related improvement for peak entropy was driven primarily by happy expressions. There was no relationship between quantitative indices and clinical measures of mood (depression, anxiety) and motor disease severity. The effects of levodopa on Parkinson's disease voluntary facial movement and on timing were robust and consistent with those of levodopa on other intentional movements in Parkinson's disease. This improvement possibly occurred because of levodopa enhanced activation of face representation areas in fronto-cortical regions or because of less movement-based suppression.