Moderate Disease Research Articles

Lymphocyte B Subtypes in Peripheral Blood: A Prognostic Biomarker for COVID-19 Patients.

In view of the scientific gap in knowledge of the involvement of the B-cell compartment and clinical prognostic in SARS-CoV-2 infection, this work aims to evaluate the B-cell subsets and the presence of specific IgM and IgG, as well as neutralizing antibodies against SARS-CoV-2, in unvaccinated patients diagnosed with COVID-19. This study included 133 patients with COVID-19. Cellular components were assessed by flow cytometry, and immunoglobulin levels and reactivity were measured by indirect enzyme-linked immunosorbent assay. Our results showed no changes in less differentiated B cells. However, non-switched memory B cells (NS-MBCs) and class-switched memory B cells (CS-MBCs) were reduced in the patients with moderate disease. Also, plasmablasts and double-negative (DN) or "atypical" memory B cells were increased in groups of patients with moderate to critical conditions. In addition, the production of IgM, IgG, and neutralizing antibodies against SARS-CoV-2 demonstrated a positive correlation between the positivity of antibodies against SARS-CoV-2 and disease severity. Besides being related to the development of a more severe course of the disease, the increase in DN B-cell count also contributed to a poorer disease outcome in patients with a higher percentage of these cells. On the other hand, we observed an increase in the absolute number of CS-MBCs in patients with greater chances of survival. This study demonstrates that the B-cell compartment may contribute to the development of clinical symptoms of COVID-19, with changes in B-cell subset counts linked to disease course and patient prognosis.

Dysphagia Pattern in Early to Moderate Parkinson's Disease Caused by Abnormal Pharyngeal Kinematic Function.

Airway invasion is common in patients with Parkinson's disease (PD) and can cause serious complications. However, a PD-related dysphagic pattern has not been clearly elucidated. In this study, 53 patients with early to moderate PD were enrolled to undergo a videofluoroscopic study of swallowing evaluation (VFSS) and a battery of neuropsychological assessments. A set of VFSS variables (three visuoperceptual, nine temporal, and six spatial) were measured. The main effects of bolus viscosity and volume on airway invasion were calculated. Statistical analyses were performed to determine key kinematic factors of airway invasion for swallowing each bolus type. Airway invasion frequency was significantly higher for liquid boluses (liquid vs. pudding P < 0.001; liquid vs. honey P = 0.006). Laryngeal vestibule closure reaction time (LVCrt) was the key kinematic factor of airway invasion for 3ml liquid swallow (P = 0.040), anterior displacement of hyoid bone was the key kinematic factor for both 5ml and 10ml liquid swallows (P = 0.010, 0.034, respectively). Male sex and advanced Hoehn and Yahr stage were significantly related to reduced anterior displacement of hyoid bone. These results reveal the dysphagic pattern related to PD, demonstrating that prolonged LVCrt and reduced anterior displacement of hyoid bone are two crucial kinematic factors contributing to airway invasion during the liquid swallow. In addition, hyoid bone dysfunction was correlated with disease severity and male sex. Our findings warrant further investigation of the pathophysiological mechanism of dysphagia in PD and would guide clinical intervention.

Serum Trefoil Factor-3 Predicts Survival in Peripheral Artery Disease.

Trefoil factor 3 (TFF3) has been studied in processes leading to atherosclerosis. Data are scarce in manifest disease and missing in peripheral artery disease (PAD). This study aims to elucidate TFF3 with disease stages, degrees of atherosclerosis, and outcomes. TFF3 was measured in serum in 364 PAD patients without critical limb ischemia and mild to moderate chronic kidney disease (CKD). Mortality data were retrieved from the Austrian central death registry (median observation 9.6years). Survival analyses were performed using Cox regression and the Kaplan-Meier method. A negative association between ankle-brachial index and TFF3 (P < .001) was observed, while levels were similar in asymptomatic and symptomatic PAD. TFF3 increased with history of cardiovascular and cerebrovascular disease (P < .001). TTF3 was associated with the estimated glomerular filtration rate (R = -0.617, P < .001) and urinary albumin-creatinine ratio (R = 0.229, P < .001). One SD increase in TFF3 showed a worsening in all-cause mortality (hazard ratio 1.68, CI 1.37-2.05) which persisted after multiple adjustment for cardiovascular risk, inflammatory, and angiogenetic markers (hazard ratio 1.35, CI 1.01-1.81). This study is the first to link TFF3 with both disease markers and outcomes in PAD. TFF3 demonstrated associations with renal function, PAD severity measured by ankle-brachial index, and additional atherosclerotic burden in PAD.

Favipiravir for treating COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to challenge the health workforce and societies worldwide. Favipiravir was suggested by some experts to be effective and safe to use in COVID-19. Although this drug has been evaluated in randomized controlled trials (RCTs), it is still unclear if it has a definite role in the treatment of COVID-19. To assess the effects of favipiravir compared to no treatment, supportive treatment, or other experimental antiviral treatment in people with acute COVID-19. We searched the Cochrane COVID-19 Study Register, MEDLINE, Embase, the World Health Organization (WHO) COVID-19 Global literature on coronavirus disease, and three other databases, up to 18 July 2023. We searched for RCTs evaluating the efficacy of favipiravir in treating people with COVID-19. We used standard Cochrane methodological procedures for data collection and analysis. We used the GRADE approach to assess the certainty of evidence for each outcome. We included 25 trials that randomized 5750 adults (most under 60 years of age). The trials were conducted in Bahrain, Brazil, China, India, Iran, Kuwait, Malaysia, Mexico, Russia, Saudi Arabia, Thailand, the UK, and the USA. Most participants were hospitalized with mild to moderate disease (89%). Twenty-two of the 25 trials investigated the role of favipiravir compared to placebo or standard of care, whilst lopinavir/ritonavir was the comparator in two trials, and umifenovir in one trial. Most trials (24 of 25) initiated favipiravir at 1600 mg or 1800 mg twice daily for the first day, followed by 600 mg to 800 mg twice a day. The duration of treatment varied from five to 14 days. We do not know whether favipiravir reduces all-cause mortality at 28 to 30 days, or in-hospital (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.46; 11 trials, 3459 participants; very low-certainty evidence). We do not know if favipiravir reduces the progression to invasive mechanical ventilation (RR 0.86, 95% CI 0.68 to 1.09; 8 trials, 1383 participants; very low-certainty evidence). Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory) (RR 1.04, 95% CI 0.44 to 2.46; 4 trials, 670 participants; low-certainty evidence). We do not know if favipiravir reduces the time to clinical improvement (defined as time to a 2-point reduction in patients' admission status on the WHO's ordinal scale) (hazard ratio (HR) 1.13, 95% CI 0.69 to 1.83; 4 trials, 721 participants; very low-certainty evidence). Favipiravir may make little to no difference to the progression to oxygen therapy (RR 1.20, 95% CI 0.83 to 1.75; 2 trials, 543 participants; low-certainty evidence). Favipiravir may lead to an overall increased incidence of adverse events (RR 1.27, 95% CI 1.05 to 1.54; 18 trials, 4699 participants; low-certainty evidence), but may result in little to no difference inserious adverse eventsattributable to the drug (RR 1.04, 95% CI 0.76 to 1.42; 12 trials, 3317 participants; low-certainty evidence). The low- to very low-certainty evidence means that we do not know whether favipiravir is efficacious in people with COVID-19 illness, irrespective of severity or admission status. Treatment with favipiravir may result in an overall increase in the incidence of adverse events but may not result in serious adverse events.

Emerging Role of Interleukin-38 (IL-38) in the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an incurable autoimmune disease. The role of interleukin-38 (IL-38), an anti-inflammatory cytokine, in RA is not fully understood, and its clinical relevance in RA remains unclear. This study aims to investigate the correlation of IL-38 with disease activity and the clinical manifestation of RA. In this cross-sectional study, patients with treatment-naïve RA (n = 63) and healthy controls (HC) (n = 60) were consecutively enrolled over a 15-month period. Patients with RA were categorized into three subgroups-low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)-using the Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP). Circulating levels of IL-38, tumour necrosis factor (TNF), IL-6, IL-17, IL-1β, and 25(OH)D were assessed using enzyme-linked immunosorbent assay (ELISA). Clinical data, including duration, tender joints count (TJC), swollen joints count (SJC), patient global assessment (PGA), evaluator global assessment (EGA), bone mineral density (BMD), clinical disease activity index (CDAI), simplified disease activity index (SDAI), DAS28-CRP, joint musculoskeletal ultrasound (MSUS), and serological indicators were recorded. We determined the correlation between IL-38 and disease activity, as well as clinical manifestation in RA. At the macroscopic level, musculoskeletal ultrasonography of joints in different stages of disease activity in RA suggests that, as the disease progresses, arthritis in the hand becomes more severe, accompanied by synovial thickening and pronounced blood flow signals in the joint area. The expression of IL-38, TNF, IL-6, IL-17 and IL-1β significantly increased in patients with RA compared to HC. Noteworthy differences were observed in the blood flow signal score, synovial signal score, IL-38, TNF, IL-6, IL-17 and IL-1β among the three subgroups (LDA, MDA and HDA). As disease activity increased in patients with RA, the blood flow signal score, synovial signal score and expression of TNF, IL-6, IL-17 and IL-1β exhibited a gradual increase, while the expression of IL-38 showed the opposite pattern. Inverse correlations were identified between IL-38 and pro-inflammatory cytokines (IL-6, IL-17), as well as key clinical parameters, including disease duration, SJC, TJC and DAS28-CRP score. IL-38, intricately linked to the pathogenesis of RA, emerges as a promising therapeutic target for the management of this debilitating disease.

Very low dose glucocorticoid therapy in rheumatoid arthritis: Impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal.

We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off, and 23% had permanently discontinued very low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very low-dose GCs cessation (OR 1.1, 95% CI 1.03-1.14 for any 1-year decrease; p= 0.001). A significant association existed between ongoing utilization of very low-dose GCs and persistent moderate disease activity. Use of very low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.

Inter-hospital moderate and advanced Alzheimer's disease detection through convolutional neural networks

Electroencephalography (EEG) has been a fundamental technique in the identification of health conditions since its discovery. This analysis specifically centers on machine learning (ML) and deep learning (DL) methodologies designed for the analysis of electroencephalogram (EEG) data to categorize individuals with Alzheimer's Disease (AD) into two groups: Moderate or Advanced Alzheimer's dementia.Our study is based on a comprehensive database comprising 668 volunteers from 5 different hospitals, collected over a decade. This diverse dataset enables better training and validation of our results. Among the methods evaluated, the CNN (deep learning) approach outperformed others, achieving a remarkable classification accuracy of 97.45% for patients with Moderate Alzheimer's Dementia (ADM) and 97.03% for patients with Advanced Alzheimer's Dementia (ADA). Importantly, all the compared methods were rigorously assessed under identical conditions. The proposed DL model, specifically CNN, effectively extracts time domain features from EEG data in time, resulting in a significant reduction in learnable parameters and data redundancy.

Correlation of ABO Blood Group Susceptibility to Disease Severity of SARS-COV-2: An Original Research

ABSTRACT COVID-19, the Ecumenical Pandemic that hit Wuhan, Hubei Province, China, in 2019 has instigated an emergency situation all over the globe. Current scientific corroborations highlighted the role of zoonotic cross-over species transmission for the spread of the deadly virus SARSCoV2. The proposition of ABO blood grouping to susceptibility for various infectious diseases has been documented in the past since blood group antigens constitute polymorphic traits that are inherited among humans, therefore are frequent targets in epidemiological studies. Aim: To correlate the ABO blood group susceptibility to disease severity in COVID-19-positive cases among Indian populations. Objectives: Association of ABO blood group patterns to disease severity in COVID-19-positive cases. Materials and Methods: A cross-sectional, observational study design was conducted among 700 confirmed COVID-19-positive cases admitted to the tertiary health care center in Maharashtra, India. The data collected were subjected to statistical analysis. Results: Blood group ‘A’ positive was frequent (40%) in severe COVID-19 (E group) disease, and ‘O’ positive blood group was frequent in moderate COVID-19 disease (34.62%). Conclusion: ABO Blood grouping can be used as one of the efficient biomarker for COVID-19, thereby providing a new platform for therapeutic applications in the field of research.

Cardiovascular risk markers (computed tomography‑coronary artery calcium and carotid intima‑media thickness) in patients with rheumatoid arthritis and controls.

Chronic inflammatory diseases, such as arthritis have been linked to a higher risk of developing cardiovascular disease. The present study examined the association between carotid intima-media thickness (CIMT) and coronary artery calcium (CAC), as well as the cardiovascular risk in patients with rheumatoid arthritis (RA). Additionally, the present study used 28 measures to calculate the disease activity score (DAS). To compare healthy controls with patients with RA, a case-control study was conducted that assessed CAC and CIMT in patients with the disease. A total of 45 healthy individuals and 45 patients with a diagnosis of RA were included in the study. With an average age of 50.66±12.35 years, the ages of the participants varied from 24 to 80 years. In both the control and RA patient groups, the sex ratio was 60%. The RA patient group had 53.3% female participants. There were significant variations in the levels of serum urea, potassium, magnesium, serum alkaline phosphatase, serum glutamic pyruvic transaminase, total leucocyte count, erythrocyte sedimentation rate, C-reactive protein (CRP) and lipids [apart from triglycerides and very low-density lipoprotein (VLDL)]. There was a substantial difference in the scores between patients with RA and the controls as regards CAC. A mild-severe risk of coronary artery disease was observed in 55.6% of RA cases and 4.4% of the controls (all mild). Both CIMT thickness and the CAC score exhibited a significant correlation with CRP, serum cholesterol, serum triglycerides, serum low-density lipids and serum VLDL. The DAS of patients ranged between 4.4 and 8.2 (mean, 5.81±0.91). A moderate disease activity was noted in the remaining patients, whereas 66.7% exhibited a high disease activity (DAS >5.2). On the whole, the present study demonstrates that conventional risk factors for cardiovascular disease, such as dyslipidemia, are consistent with both CIMT and CAC. The risk of developing atherosclerosis may be substantially increased by chronic inflammation, as the DAS score corresponds with CIMT and CAC.

Prevalence of pulmonary artery dilation in non-cystic fibrosis bronchiectasis: a computed tomography analysis from a cohort of the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry.

Although pulmonary artery (PA) dilation is independently associated with significant morbidity and mortality in patients with pulmonary diseases irrespective of diagnosed pulmonary hypertension, its relationship with nontuberculous mycobacteria (NTM) is unknown. The Bronchiectasis and NTM Research Registry is a multicenter registry created to foster research in non-cystic fibrosis (CF) bronchiectasis and NTM lung disease. The majority of patients with non-CF bronchiectasis at Oregon Health & Science University have NTM infections. To determine the prevalence of PA dilation in these patients and its association with supplemental oxygen use, severity of bronchiectasis, tobacco use, and NTM in the sputum culture, we evaluated the chest computed tomography (CT) scans from 321 patients in a cross-sectional analysis. We measured the severity of bronchiectasis by applying modified Reiff criteria and measured the diameters of the PA and aorta (Ao), with PA dilation defined as a PA:Ao ratio >0.9. In our cohort, the mean age was 67.3 years and 83.2% were female. The mean modified Reiff score was 7.1, indicating moderate disease severity. Forty-two patients (13.1%) were found to have PA dilation. PA dilation was positively associated with the use of supplemental oxygen (P<0.001), but there was no association between PA dilation and NTM infection.

Defining criteria for disease activity states in juvenile dermatomyositis based on the Juvenile Dermatomyositis Activity Index

ObjectivesTo develop and validate the cut-offs in the Juvenile DermatoMyositis Activity Index (JDMAI) to distinguish the states of inactive disease (ID), low disease activity (LDA), moderate disease activity (MDA) and...

Characteristics and prevalence of clinical remission of rheumatoid arthritis in a nationwide study from Indonesia

AbstractAimTo investigate the clinical characteristics, DMARD treatment pattern, remission rate, and factors associated with disease remission of rheumatoid arthritis (RA) patients in Indonesia.MethodA multicenter survey was conducted in 2019–2020 involving 16 hospitals in Indonesia. Inclusion criteria were RA patients who fulfilled the 2010 ACR/EULAR classification criteria, were aged ≥18 years, and have been treated with 1 DMARD or more for at least 6 months, with exclusion criteria being the co‐existence of other autoimmune diseases or pain syndromes. Disease activities and remission rate were defined using DAS28‐ESR.ResultsA total of 870 patients were completed for analysis. Remission was achieved in 24.5% of patients, while low disease activity in 18.5%, moderate disease activity in 44.6%, and high disease activity in 12.4%. The distribution of conventional DMARDs from subjects was methotrexate 69.9%, leflunomide 15.9%, sulfasalazine 12.0%, chloroquine/hydroxychloroquine 8.9%, and cyclosporine 4.8%. Patients treated with biologic DMARDs were only 0.3%. The mean methotrexate dose was 11.2 ± 4.0 mg/week, and the mean methotrexate duration was 45.1 ± 36.6 months. The majority of patients received glucocorticoids (65.5%). 71.1% received DMARD monotherapy, while 28.9% had combined DMARDs. According to the multivariate analysis, delayed time to diagnosis and treatment (&gt;6 months), DMARD monotherapy, and glucocorticoid use were negatively associated with disease remission.ConclusionThe remission rate of Indonesian RA patients is 24.5%, and low disease activity is 18.5%. Methotrexate and leflunomide are the most frequent conventional DMARDs used. Delayed diagnosis, delayed treatment, and DMARD monotherapy contributed to the current low remission rate in Indonesia.

A real-world disproportionality analysis of mesalazine data mining of the public version of FDA adverse event reporting system.

Background: Mesalazine, a preparation of 5-aminosalicylic acid, is a medication widely used in clinical practice as a first-line therapy in the treatment of mild and moderate inflammatory bowel disease. However, the long-term safety of mesalazine in large sample population was unknown. The current study was to assess mesalazine -related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of mesalazine -associated AEs. Results: Out of 14,149,980 reports collected from the FDA Adverse Event Reporting System database, 24,284 reports of mesalazine -associated AEs were identified. A total of 170 significant disproportionality preferred terms conforming to the four algorithms simultaneously were retained. The most common AEs included colitis ulcerative, diarrhoea, condition aggravated, crohn's disease, fatigue, abdominal pain, nausea, haematochezia, which were corresponding to those reported in the specification and clinical trials. Unexpected significant AEs as dizziness, drug ineffective, drug hypersensitivity, infection, off label use, weight decreased, decreased appetite, arthralgia, rash might also occur. The median onset time of mesalazine -related AEs was 1,127days (interquartile range [IQR] 1,127-1,674days), and most of the cases occurred 2years later (n = 610, 70.93%) and within the first 1month (n = 89, 10.35%) after mesalazine initiation. Conclusion: Results of our study were consistent with clinical observations. We also found potential new and unexpected AEs signals for mesalazine, suggesting prospective clinical studies were needed to confirm these results and illustrate their relationship. Our results could provide valuable evidence for further safety studies of mesalazine.

Clinical and Demographic Profiling of Patients with Spondyloarthritis and Its Association with Disease Activity in a Tertiary Hospital in Surabaya, Indonesia

Introduction: The assessment of disease activity is crucial for effectively managing chronic diseases like spondyloarthritis (SpA). Establishing the relationship between disease activity, demographic, and clinical factors is essential for better disease management. This study aimed to delve into the demographic and clinical characteristics of patients at Dr. Soetomo General Academic Hospital, a tertiary hospital in Surabaya, Indonesia, contributing to a comprehensive understanding of SpA occurrences in Surabaya.Methods: Data were obtained from 38 SpA patients’ data classified using ASAS 2009 criteria at Dr. Soetomo General Academic Hospital, excluding individuals with SLE, gout, RA, and septic arthritis. Disease activity was measured using ASDAS-CRP. Association analysis between disease activity, clinical parameters, and demographics was conducted using Mann-Withney U test and Spearman correlation test.Results: Results indicated a male-to-female ratio of 8:30, with patients having a median age of 48 (95% CI: 41-53) and most of the patients had a senior high school education (42.11%). The patients exhibited a mean BMI of 25.19 ± 3.77, a median disease duration of 8.5 (95% CI: 5-10) years, and a median CRP value of 0.2 (95% CI: 0.1-0.5) mg/dL. The majority displayed moderate disease activity, with a median ASDAS-CRP score of 2 (95% CI: 1.5-2.7). Interestingly, no significant correlation was found between disease activity using ASDAS-CRP and the demographic or clinical parameters studied.Conclusion: Disease activities were found not to have correlations with the demography and clinical parameters of patients with SpA from Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. This emphasizes the necessity for further research to comprehend the intricate relationship between disease activity and diverse influencing factors.

Clinical and laboratory characteristics of patients associated with severe COVID-19 infection and death at a tertiary care hospital in Sri Lanka

Introduction: COVID-19 caused a massive burden to the health sector in Sri Lanka. This study aims to describe the clinical and laboratory characteristics associated with severe COVID infection and death in patients with moderate or severe COVID-19.Methods: This descriptive cross-sectional study was carried out from November 2021-June 2022 at a Teaching Hospital in Colombo. Consecutive sampling of adults admitted to hospital with moderate or severe COVID-19 was done. Data was collected from patient interviews and medical records.Results: The study population consisted of 388 patients. Mean age (SD) was 61.1 (±14.7) years and 56.4% were men. In-hospital deaths were 39%. Shortness of breath was the commonest presenting complaint (89.4%). Death was more common among those with the following symptoms as opposed to those without; fever (49.3% vs 27.7%, p&lt; .001), cough (64.2% vs 23.2%, p&lt; .001) and chest pain (70.5% vs 34.9%, p &lt; .001). Other factors associated with death were male gender (44.2% vs 32.1 %, p= .016), age &gt;60years (66.5 vs 10.1, p&lt; .001), diabetes (47.2% vs 23.7%, p&lt; .001), hypertension (61% vs 23.5, p&lt; .001), ischemic heart disease (78.6% vs 30.1%, p&lt; .001), COPD (90.0% vs 35.8%, p&lt; .001) and smoking (60.3% vs 34%, p&lt; .001). Symptoms, demographics and comorbidities associated with severe disease compared to moderate disease were similar to those associated with in-hospital deaths. High white cell count, high CRP, low pH and low SpO2 on admission were significantly associated with death as well as severe disease. Conclusions: Clinical and laboratory characteristics associated with death in patients with COVID-19 were similar to those with severe COVID. These parameters help to detect patients who need close monitoring and more intensive management.

Development and evaluation of emulsified reference materials for magnetic resonance imaging

Hepatic steatosis is characterized by an abnormal accumulation of lipids within hepatocytes. Magnetic resonance imaging (MRI) is a widely used noninvasive method that can accurately and objectively quantify liver fat. To evaluate the accuracy of the quantitatively measured fat fraction, stable and homogenous qualified material is needed as a reference. Surfactant-free micro-emulsions of three fat fractions I, II, and III, corresponding to (9.12 ± 0.02)%, (18.32 ± 0.04)%, and (27.86 ± 0.05)%, respectively, were prepared using a high-intensity focused ultrasonic emulsification technique. The targeted fat fraction of 10%–30% covers the range of grade I moderate non-alcoholic fatty liver disease, which occurs in the early stages that require early detection. Water contents as the main component of the emulsified reference materials (RMs) were determined using the Karl Fisher titration method to evaluate the stability and homogeneity of the RMs. The water contents of fat fraction I, II, and III were (89.12 ± 1.08)%, (79.87 ± 0.81)%, and (72.71 ± 1.29)%, respectively. The RMs were stable for six months and showed good homogeneity with both standard deviations between and within units in the range of 0.3%–0.6%. The physical phantom consisted of nine vials of RMs surrounded by agarose gel. The phantom was scanned on 3 T MRI (Siemens MAGNETOM Vida, Siemens Healthineers, Erlangen, Germany). The correlation between the measured proton density fat fraction values and the fabricated fat fraction values was evaluated using linear regression analysis. The slope of the linear fitting was 0.99, and the intercept was −0.88%. These results show that the developed RMs can provide a reference value for the measured fat fraction from a medical imaging system to evaluate the effectiveness of a measurement procedure. It is also expected that the developed RMs can be utilized to harmonize the measured values across multi-site.

IDENTIFICATION OF DISEASE SEVERITY DEFINITIONS FOR ULCERATIVE COLITIS AND CROHN’S DISEASE

Abstract BACKGROUND Evidence suggests that, in patients with ulcerative colitis (UC) or Crohn’s disease (CD), those with moderate disease may achieve better outcomes with vedolizumab than those with severe disease. However, no consensus definition of moderate disease exists for UC or CD, as confirmed by a comprehensive literature review published in 2016.1 We aimed to identify definitions of disease severity for UC and CD in studies published since the approval of vedolizumab. METHODS The first stage of the research comprised a systematic literature review (SLR) that complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement and was registered prospectively with PROSPERO (CRD42023427948). Literature searches were conducted in Embase, MEDLINE, and the Cochrane Library databases on May 16, 2023 to identify publications from 2015 onwards. Title and abstract screening, followed by full-text review was undertaken by two blinded reviewers, with discrepancies resolved by a third reviewer. Data on disease severity indices and thresholds used to define mild, moderate, and/or severe disease were extracted from eligible primary publications. RESULTS Data were extracted from 119 eligible publications (Figure 1), of which 109 related to UC only, 7 to CD only, and 3 to both UC and CD. For UC, the most common disease severity index was Truelove and Witts’ criteria (N = 82), followed by Mayo score or one of its derivatives such as partial Mayo score or Mayo sub-score (N = 29), Lichtiger index (N = 9), Montreal classification (N = 4), Rachmilewitz score (N = 3), and Oxford criteria (N = 3). The definitions identified for mild and moderate disease were similar across studies; however, numerical thresholds used to define moderate and severe disease with Mayo score, partial Mayo score, and Lichtiger index overlapped (Figure 2). For CD, the Crohn’s Disease Activity Index (CDAI) (N = 6) was the most commonly used disease severity index, followed by the Harvey–Bradshaw index (HBI) (N = 2). Moderate disease was defined as a CDAI score of 200–450 or 220–450 or a HBI score of 8–16. CONCLUSION For UC, the thresholds used to define moderate disease were similar across studies but overlapped with those used for severe disease in some cases. Too few CD publications were identified to draw robust conclusions, likely due to the exclusion of those describing patients with mild-to-moderate or moderate-to-severe disease without further stratification in the title or abstract. A targeted literature review of publications reporting phase 3 clinical trials of drugs for UC or CD is ongoing; the thresholds of all measurements used to stratify the patient cohorts in these trials will be extracted to further understand the characteristics of patients with moderate disease. 1. Peyrin-Biroulet L, et al. Clin Gastroenterol Hepatol. 2016;14(3):348-354.e17. Figure 1 PRISMA flow diagram. Figure 2 Numerical ranges used to define mild, moderate, and severe disease for UC.

CLINICAL, BIOCHEMICAL, AND INTESTINAL ULTRASONOGRAPHY RESPONSE TO CURCUMIN-QINGDAI (CURQD) COMBINATION IN PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CASE SERIES

Abstract BACKGROUND There are few FDA-approved therapies for pediatric patients with inflammatory bowel disease (IBD). Clinical remission rates plateau at 60%, even with the currently available biologic therapies. Nutraceuticals are novel alternative treatments that can be used as adjunct treatments. AIM In this case series of 8 patients, we aim to present the clinical and radiological response to a novel nutraceutical agent, CurQD, composed of QingDai (Indigo Naturalis) and Curcumin. METHODS Patients included required a baseline pre-treatment clinical assessment and at least a single follow-up examination. Clinical status was evaluated based on the Physician General Assessment (PGA, determined independently from the clinical scoring systems) and the pediatric Crohn’s disease activity index (PCDAI) or the pediatric ulcerative colitis activity index (PUCAI), as appropriate. Baseline biomarkers (Hgb, ESR, CRP, albumin, and calprotectin(FC)) were collected pre and post-treatment when available. When available, intestinal ultrasound (IUS) features were also noted. On the IUS, bowel wall thickness (BWT, in mm) and color Doppler signaling (measured by the modified Limberg score graded 0,1,2, or 3 based on severity) were collected. The longitudinal changes were demonstrated on the most inflamed segment. Considering the small sample size, only descriptive statistics were applied. RESULTS Primary therapies received included anti-TNFα for 3 patients, ustekinumab in 3 patients, 1 on vedolizumab, and mesalamine in 1. Baseline assessment was done at a median time of 1.8 weeks (IQR 0.9-3.6 weeks) before starting the supplement, and the follow-up was 3.9 weeks (IQR 2.8-5.4 weeks) after starting the supplement. Two patients were in clinical remission at baseline but had active disease based on Doppler activity on IUS, 3 patients had mild active disease, and 3 patients had either moderate or severe disease activity. At follow-up, all patients but one were in clinical remission. (Table 1) Median baseline FC decreased from 1047.4 ug/g (IQR 532.4-1107) to 27.1 (IQR 27.5-341.3). Five patients had complete IUS information. When isolating the most inflamed segment on IUS, all patients demonstrated a response to treatment, noted by a decrease in BWT and/or a decrease in Doppler signaling. (Figure 1) No patient had a baseline therapy change after their follow-up. One patient reported abdominal bloating after starting CurQD and discontinued the product after five weeks. CONCLUSION CurQD is a promising nutraceutical that may assist in breaking the therapeutic ceiling of biological therapies in IBD. Based on this small experience, a larger randomized controlled trial in children would be needed to assess the safety and efficacy of this product in this vulnerable patient group. Furthermore, IUS is a practical tool for evaluating response to therapy in a pragmatic clinical setting. Table 1 Change in clinical disease scores in patients receiving CurQD Figure 1 Description of changes in a) bowel wall thickness (BWT) and b) color Doppler signaling (measured by the modified Limberg score) in patients treated with CurQD.

In-hospital real-time prediction of COVID-19 severity regardless of disease phase using electronic health records.

Coronavirus disease 2019 (COVID-19) has strained healthcare systems worldwide. Predicting COVID-19 severity could optimize resource allocation, like oxygen devices and intensive care. If machine learning model could forecast the severity of COVID-19 patients, hospital resource allocation would be more comfortable. This study evaluated machine learning models using electronic records from 3,996 COVID-19 patients to forecast mild, moderate, or severe disease up to 2 days in advance. A deep neural network (DNN) model achieved 91.8% accuracy, 0.96 AUROC, and 0.90 AUPRC for 2-day predictions, regardless of disease phase. Tree-based models like random forest achieved slightly better metrics (random forest: 94.1% of accuracy, 0.98 AUROC, 0.95 AUPRC; Gradient boost: 94.1% of accuracy, 0.98 AUROC, 0.94 AUPRC), prioritizing treatment factors like steroid use. However, the DNN relied more on fixed patient factors like demographics and symptoms in aspect to SHAP value importance. Since treatment patterns vary between hospitals, the DNN may be more generalizable than tree-based models (random forest, gradient boost model). The results demonstrate accurate short-term forecasting of COVID-19 severity using routine clinical data. DNN models may balance predictive performance and generalizability better than other methods. Severity predictions by machine learning model could facilitate resource planning, like ICU arrangement and oxygen devices.

LIQUID-BIOPSY FOR ASSESSING SEVERITY OF INFLAMMATORY BOWEL DISEASE VIA PLASMA MICROBIAL CELL-FREE DNA

Abstract Plasma cell-free DNA (cfDNA) has emerged as a robust biomarker utilized in multiple applications that span cancer screening, diagnosis and monitoring, prenatal testing, and characterization of organ health post-transplantation. Cell-free DNA-based assays leverage the occurrence of processed extracellular DNA that produce unique signatures to discern a variety of biological states, disease manifestations, as well as forms of cell death. Similar to human cells, microbes produce cfDNA when they turnover, providing evident clinical utility in diagnosing and treating deep-seated infections in immunocompromised patients. Here, we describe the use of plasma microbial cell-free DNA (mcfDNA) as a unique means to assess inflammatory bowel disease type and severity. A total of 392 plasma samples encompassing remission and active (mild, moderate, severe) Crohn’s disease (N=196) and ulcerative colitis (N=196) were provided by the Crohn’s and Colitis Foundation for this study. All samples were derived from patients who had an endoscopic assessment within a 30-day window of plasma collection. Our classifiers, based solely on plasma mcfDNA signatures, are able to discriminate between Crohn’s disease, Ulcerative colitis, or otherwise healthy patient populations with an AUC &amp;gt;0.95. Similarly, a second set of classifiers are able to distinguish between endoscopically validated remission, mild, moderate, and severe disease cases (as determined by Mayo Endoscopic score or Crohn’s disease activity index) with AUCs &amp;gt;0.75. These results correspond to greater than 37% (UC) and 18% (CD) increase in sensitivity in comparison to standard of care measurements via fecal-calprotectin and high sensitivity-C-reactive protein for this cohort. Upon investigation, critical features in our classifiers correspond with well-known signatures from microbes associated with IBD or well-curated from the human microbiome. The use of mcfDNA for IBD diagnosis and assessment of disease severity may provide clinicians and patients a valuable non-invasive means to gain additional insight into disease progression in a routine manner. Further opportunities to leverage these signatures to predict response to therapy, and validate classifier performance on an independent cohort are currently being explored.