Improvement In Disease Severity Research Articles

The Impact of Statins on Disease Severity and Quality of Life in Patients with Psoriasis: A Systematic Review and Meta-Analysis.

Psoriasis, a chronic autoimmune condition, imposes significant burdens on patients' well-being. While corticosteroid medications are commonly used, their prolonged use presents risks. Statins, known for their immunoregulatory and anti-inflammatory properties, have emerged as potential alternatives. Previous reviews indicated that statins might improve psoriasis symptoms but showed inconsistent results and lacked meta-analyses that generated pooled effect estimates. Therefore, this study addresses this gap by providing a comprehensive overview of the impact of statins on psoriasis severity and quality of life (QoL) for patients with psoriasis. A thorough search of four electronic databases (PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Science Direct) was conducted for relevant studies published before April 2024. Seven studies involving 369 patients were included. This meta-analysis showed a statistically significant reduction in PASI scores at week 8 with statin treatment (MD = -1.96, 95% CI [-3.14, -0.77], p = 0.001). However, no statistically significant difference was found between statins and placebo at week 12 (MD = 0.19, 95% CI [-0.18, 0.55]). Additionally, DLQI scores indicated a significant improvement in quality of life with statins compared to placebo (MD = -3.16, 95% CI [-5.55, -0.77]). Statins can improve disease severity and quality of life in psoriasis patients, suggesting the potential benefits of statin therapy. However, further research is needed to determine the optimal treatment duration, address outcome heterogeneity, and explore additional benefits such as cholesterol and triglyceride reduction.

Enhanced Therapeutic Effects of Human Mesenchymal stem Cells Transduced with Secreted Klotho in a Murine Experimental Autoimmune Encephalomyelitis Model.

Treatment of multiple sclerosis (MS) remains a major challenge. The aim of this study was to evaluate the therapeutic potential of mesenchymal stem cells (MSCs) engineered with secreted Klotho (SKL) in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. EAE was induced in mice. MSCs or MSCs engineered with SKL (SKL-MSCs) were administered to EAE mice at the onset of disease. Hematoxylin-eosin and luxol fast blue staining were performed to evaluate histopathological changes. Expression of pro-inflammatory (TNF-α, IFN-γ, and IL-17) and anti-inflammatory (IL-10) cytokines was determined in the spinal cord using real-time PCR. Spinal cords were then processed for immunohistochemistry of the aforementioned cytokines. The frequencies of Th1, Th17, and regulatory T (Treg) cells were evaluated by flow cytometry of the spleen. The results showed that SKL-MSCs decreased clinical scores and reduced demyelination and inflammatory infiltration in the spinal cord more significantly than MSCs. Compared to MSCs, SKL-MSCs also exhibited a more profound capability of decreasing expression of TNF-α, IFN-γ, and IL-17 and increasing expression of IL-10 in the spinal cord with an enhanced homing to the inflamed tissue. Moreover, SKL-MSCs decreased the frequencies of Th1 and Th17 cells and increased the frequency of Treg cells in the spleen more potently than MSCs. Taken together, these findings demonstrate that SKL overexpression enhances the therapeutic potential of MSCs, as evidenced by significantly improved disease severity, decreased inflammation and tissue damage in the spinal cord, and a promoted shift in the Th17/Treg balance towards the anti-inflammatory Treg side in the EAE mice.

Effect and mechanism of aqueous extract of Strychni Semen on bone destruction in rats with type Ⅱ collagen-induced rheumatoid arthritis

To investigate the mechanism of action of aqueous extract of Strychni Semen(SA) on bone destruction in rats with type Ⅱ collagen-induced arthritis(CIA), the SD rats were randomly divided into normal group, model group, low, medium, and high dose(2.85, 5.70, and 11.40 mg·kg~(-1)) groups of SA, and methotrexate group. Except for the normal group, the CIA model was prepared for the other groups. After the second immunization, different doses of SA were given to the low, medium, and high dose groups of SA once a day, and the methotrexate group was given once every three days. 0.3% sodium hydroxymethylcellulose(CMC-Na) was given once a day to the normal and model groups for 28 d. The clinical score of arthritis was evaluated every three days. Micro computed tomography(Micro-CT) method was used to evaluate the degree of bone destruction. Histopathological changes in the joint tissue and the number of osteoclasts in CIA rats were evaluated by hematoxylin-eosin(HE) staining and tartrate-resistant acid phosphatase(TRAP) staining. The expression of interleukin-1β(IL-1β) in the joint tissue of rats was detected by immunohistochemistry. Western blot was used to detect key protein expression in mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathways in the joint tissue of rats. The results showed that different doses of SA were able to improve the red and swollen inflammatory joint and joint deformity in CIA rats to varying degrees, reduce the clinical score, inhibit synovial inflammation, vascular opacification, cartilage erosion, and bone destruction, and reduce the number of TRAP-positive cells in bone tissue. Micro-CT results showed that the SA was able to increase bone mineral density, bone volume fraction, trabecular reduce, and trabecular number and reduce bone surface/bone volume and trabecular separation/spacing. Different doses of SA could down-regulate the protein expression of IL-1β, p-JNK, p-ERK, p-p38, PI3K, and p-Akt to varying degrees. In conclusion, SA can improve disease severity, attenuate histopathological and imaging changes in joints, and have osteoprotective effects in CIA rats, and its mechanism of action may be related to the inhibition of the overactivation of MAPK and PI3K/Akt signaling pathways.

Review of Integrative Medical Therapies for Psoriasis: The Microbiome, Probiotics, Diet, and Mindfulness

Background Psoriasis is a chronic inflammatory condition with cutaneous and systemic involvement. Although many efficacious treatment options are available, concerns regarding costs and duration of treatment have expanded interest in the role of integrative medical therapies for psoriasis. Objective In this review, we aim to provide evidence for the use of integrative medical approaches in the management of psoriasis, namely approaches utilizing the microbiome, probiotics, diet, and mindfulness. Methods PubMed/Medline and Google Scholar databases were searched from inception up to 16 August 2023 to identify clinical studies that evaluated how integrative medical therapies affect psoriasis severity. Search terms combined “psoriasis” or “psoriatic arthritis” with terms related to the microbiome, diet, and lifestyle. Results Multiple clinical studies have shown that integrative approaches can reduce psoriasis severity. Probiotic supplementation in psoriatic patients decreased PASI scores, decreased inflammatory markers, increased quality of life, and reduced the risk of disease relapse. Intermittent fasting, in the context of Ramadan, decreased PASI scores and plasma CRP levels. Low-calorie diets and low-calorie ketogenic diets have been shown to reduce psoriasis severity. Notably, combining low-calorie diets with biologics and cyclosporine synergistically improved psoriasis to a greater extent than pharmaceutical therapy alone. A gluten-free diet improved psoriasis and reduced antigliadin antibodies in those with hypersensitivity. Mindfulness therapies also improved psoriasis severity with and without phototherapy. Conclusion Several studies show that integrative medicine can be used to manage psoriasis. Specifically, probiotic supplementation, diets that promote weight loss or modulate antigliadin antibodies, and mindfulness therapies may improve disease severity.

509 - Dupilumab improves disease severity in children less than 12 years of age with moderate-severe AD: interim results from PEDISTAD real-world registry

Abstract Introduction In phase 3 studies, dupilumab significantly improved disease severity in children with moderate-to-severe atopic dermatitis (AD). However, the impact of this systemic treatment on children in real-world treatment settings is yet to be investigated. Objectives To report the real-world effectiveness and safety of dupilumab in children the PEDISTAD registry. Methods PEDISTAD (NCT03687359) is an ongoing, international, longitudinal, observational 10-year registry study in patients aged from 6 months to 11 years at enrollment with moderate-to-severe AD, whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are medically inadvisable. This interim analysis measures the effect of dupilumab on Eczema Area and Severity Index (EASI) total score and %-affected body surface area (BSA) from therapy start to up to 3 years’ follow up. Safety was also evaluated. Results A total of 214 patients received dupilumab (median treatment observation period: 16.1 months; accumulated 3-year discontinuation rate: 13.3%). The proportion of patients with clear/mild AD (EASI score <7 [range 0–28]) increased from 20.8% at therapy start to 76.7% at last observation. The mean (±SE) EASI score decreased with dupilumab use, from 19.7±1.0 at therapy start to 6.1±0.8 at last observation. The proportion of patients with <10% BSA affected by AD increased from 12.6% at therapy start to 46.5% at last observation. The mean (± SE) BSA affected decreased from 38.3%±1.7 at therapy start to 17.1%±2.0 at last observation. 24.2% of patients had adverse events, including 2.4% serious adverse events. Conclusions Dupilumab treatment significantly improved disease severity in patients aged from 6 months to 11 years in real-world practice.

A novel infant microbiome formula (SIM03) improved eczema severity and quality of life in preschool children

Altered gut microbiome composition has been reported in children with eczema and interventions that restore beneficial bacteria in the gut may improve eczema. This open-label pilot study aimed to investigate the efficacy of a novel infant microbiome formula (SIM03) in young children with eczema. Pre-school Chinese children aged 1–5 years old with eczema received SIM03 twice daily for three months. The novelty of SIM03 consists of both the use of a patented microencapsulation technology to protect the viability of unique Bifidobacterium bifidum and Bifidobacterium breve strains identified through big data analysis of large metagenomic datasets of young Chinese children. Paired stool samples at baseline and following SIM03 were analyzed by metagenomics sequencing. Generalized estimating equation was used to analyze changes in eczema severity, skin biophysical parameters, quality of life and stool microbiome. Twenty children aged 3.0 ± 1.6 years (10 with severe eczema) were recruited. Treatment compliance was ≥ 98%. SCORing Atopic Dermatitis score decreased significantly at two months (P = 0.008) and three months (P < 0.001), while quality of life improved significantly at 1, 2, and 3 months. The relative abundance of B. breve and microbial pathways on acetate and acetyl-CoA synthesis were enriched in stool samples at one month (P = 0.0014). Children who demonstrated increased B. bifidum after SIM03 showed improvement in sleep loss (P = 0.045). Relative abundance of B. breve correlated inversely with eczema extent (P = 0.023) and intensity (P = 0.019) only among patients with increased B. breve at Month 3. No serious adverse event was observed. In conclusion, SIM03 is well tolerated. This patented microbiome formula improves disease severity and quality of life in young eczematous children by enhancing the delivery of B. bifidum and B. breve in the gut. SIM03 is a potential treatment option for childhood eczema.

P086 Identification of a Novel Immunometabolic Target and Agonist for PLXDC2 for Amelioration of DSS Colitis Model in Mice

Abstract Background PLXDC2 is expressed on the cell surface of macrophage, dendritic and specific mesenchymal and epithelial cells whose activation shifts cellular metabolism and reduces oxidative stress to rebalance the immune response and decrease inflammation. It’s role in IBD pathogenesis is unknown. PLXDC2 activation improves disease severity in rheumatoid arthritis models1, while loss of PLXDC2 exacerbates the severity of disease in DSS colitis2. PX-04 is a novel, first-in-class, orally active PLXDC2 agonist. Here, we report on the consequences of activating PLXDC2 using PX-04 in an acute DSS colitis model. Methods Mice were given DSS in drinking water for seven days to induce disruption of the epithelial layer. At project initiation, mice were 8 weeks of age and began once daily dosing with 20mg/kg of PX-04 24 hours after being placed on DSS. Mice were weighed and scored daily for 15 symptoms of disease (weight loss, diarrhea, rectal bleeding, rectal inflammation, pain, &amp; overall behavior). Colons were collected and digested, and the resultant cellular suspensions were filtered to produce single cell suspensions. Colonic Lamina Propria Immune cells were isolated by Percoll gradient centrifugation. Cells were labeled with mixtures of extracellular (CD45, CD3, CD4, CD8, CD19, NK1.1, CD25, F4/80, CD11b, Gr1, CX3CR1, CD64) and intracellular (Tbet, RORγT, FOXP3, IFNγ, IL17, IL10, TNFα) antibodies in a sequential live staining in 96-well plates. Data was acquired using a FACS Celesta flow cytometer with FACSDiva software. Results Oral PX-04 treatment decreased the cumulative disease activity of mice challenged with DSS (FIG 1A). Immunologically, PX-04 affected both the adaptive and innate immune responses. First, PX-04 greatly decreased Th17 cells in the colon, while providing a slight increase to regulatory CD4+ T cells (FIG. 1C). A lower proportion of Natural Killer (NK) cells (FIG. 7D) produced IFNγ. Meanwhile, the proportion of TNF producing dendritic cells was decreased by PX-04 treatment. Conclusion Conclusion: PLXDC2 is expressed in cells relevant to IBD pathogenesis. PX-04, which binds to and activates PLXDC2, effectively decreases levels of effector T cells and myeloid cells, as well as overall disease severity in acute DSS colitis, warranting further investigation. 1Tubau-Juni et al. J Immunol 206(Supp) 2Tubau-Juni et al. Sci Rep 10(1)

Effectiveness and cost of integrated cognitive and balance training for balance and falls in cerebellar ataxia: a blinded two-arm parallel group RCT.

In patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks. Evaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA. This RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4). Compared to single-task training CIBT improved the dual-task cost of physical task [MD -8.36 95% CI (-14.47 to -2.36, p < 0.01), dual-tasking ability [-6.93 (-13.16 to -0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [-2.03 (-4.04 to -0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [-18.53 (-25.81 to -11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [-1.11 (-1.42 to -0.78); p < 0.01] and right [-0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group. We found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim. https://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501].

SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings

Background: Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.&#x0D; Methods: A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.&#x0D; Results: 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.&#x0D; Conclusions: This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.

Topical Prescription Management.

With recent advances in topical therapies for atopic dermatitis (AD), steroid-sparing options like calcineurin inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors are becoming mainstays in therapy, underscoring the importance of careful selection and usage of topical corticosteroids (TCSs) to minimize side effects. Alongside the necessity of emollient use, these steroid-sparing alternatives offer rapid itch relief and efficacy in improving disease severity. While TCSs still hold a prominent role in AD management, promising novel topical treatments like tapinarof and live biotherapeutics to modulate the skin microbiome are also discussed. Overall, the recent addition of novel topical therapies offers diverse options for AD management and underscores the importance of topical treatments in the management of AD.

The Role of Weight Loss and Nutrition in the Management of Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is an inflammatory skin condition affecting the pilosebaceous unit. It is characterized by the formation of painful nodules, abscesses, and sinus tracts in intertriginous regions. HS has numerous, well documented risk factors including obesity, metabolic syndrome, and diabetes mellitus. Weight loss is frequently recommended as a lifestyle change for patients diagnosed with HS. There is evidence that shows weight loss improves disease severity in most cases. However, there are reports of patients who have experienced stable, worsening, or de novo disease development after undergoing bariatric surgery. Nutrition is proving to be an increasingly important aspect in the management of HS. Deficiencies in micronutrients, such as Vitamin D and zinc, as well as the consumption of triggering foods including dairy and brewer’s yeast, are implicated in HS. Encouraging patients to consume a healthy diet with supplementation of micronutrients and avoidance of dairy and brewer’s yeast has been linked to decreased HS severity. Physical activity is commonly recommended to aid in weight loss, but has been understudied in HS patients. There are reports of increased levels of physical activity decreasing disease severity, but more research is needed on this topic.

Harnessing Endogenous Peptide Compounds as Potential Therapeutics for Severe Influenza.

Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT8881 is a synthetic 16-amino acid cyclic peptide form of a naturally occurring C-terminal fragment of human growth hormone with therapeutic efficacy against influenza. Shorter linear peptides are typically easier to manufacture and formulate for delivery than larger cyclic peptides. A 6-amino acid linear peptide fragment of LAT8881, LAT9997, was investigated as a potential influenza therapy. LAT9997 was evaluated for its potential to limit disease in a preclinical mouse model of severe influenza infection. Intranasal treatment of mice with either LAT8881 or LAT9997 from day 1 following influenza infection significantly improved survival outcomes. Initiating LAT9997 treatment at the onset of severe disease also significantly improved disease severity. Greater disease resistance in LAT9997-treated mice correlated with reduced lung immunopathology, damage markers, vascular leak, and epithelial cell death. Treatment reduced viral loads, cytokines, and neutrophil infiltration in the airways yet maintained protective alveolar macrophages in a dose-dependent manner. Sequential trimming of N- and C-terminal amino acids from LAT9997 revealed a structure-activity relationship. These findings provide preclinical evidence that therapeutic LAT9997 treatment limits viral burden and characteristic features of severe influenza, including hyperinflammation and lung damage. Excessive pulmonary inflammation and damage are characteristic features of severe influenza virus infections. LAT9997 is a linear peptide fragment derived from human growth hormone. This study provides preclinical evidence that therapeutic LAT9997 treatment limits viral burden, hyperinflammation, and lung damage.

Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis.

The blood-brain barrier is composed of microvascular endothelial cells, immune cells, and astrocytes that work in concert with the coagulation cascade to control inflammation and immune cell infiltration into the central nervous system. Endothelial cell dysfunction leading to increased permeability and compromised barrier function are hallmarks of neuroinflammatory and autoimmune disorders, including multiple sclerosis (MS). Therapeutic strategies that improve or protect endothelial barrier function may be beneficial in the treatment or prevention of neuroinflammatory diseases. We therefore tested the hypothesis that biasing thrombin toward anticoagulant and cytoprotective activities would provide equivalent or even additive benefit compared with standard-of-care therapeutic strategies, including corticosteroids. In a mouse model of relapsing-remitting MS, treatment with the thrombin mutant, E-WE thrombin, an engineered thrombin mutant with cytoprotective activities that is biased toward anticoagulant and cytoprotective activity, reduced neuroinflammation and extracellular fibrin formation in SJL mice inoculated with proteolipid protein (PLP) peptide. When administered at the onset of detectable disease, E-WE thrombin significantly improved the disease severity of the initial attack as well as the relapse and delayed the onset of relapse to a similar extent as observed with methylprednisolone. Both methylprednisolone and E-WE thrombin reduced demyelination and immune cell recruitment. These results provide rationale for considering engineered forms of thrombin biased toward anticoagulant and cytoprotective activity as a therapeutic strategy and perhaps an effective alternative to high-dose methylprednisolone for the management of acute relapsing MS attacks.NEW & NOTEWORTHY There are limited treatment options for mitigating acute relapsing attacks for patients with multiple sclerosis. We tested the hypothesis that harnessing the cytoprotective activity of the blood coagulation enzyme, thrombin, would provide benefit and protection against relapsing disease in a mouse model of MS. Our results provide rationale for considering engineered forms of thrombin biased toward cytoprotective activity as a therapeutic strategy and perhaps an alternative to steroids for the management of relapsing MS attacks.

Loss of NOD2 in macrophages improves colitis and tumorigenesis in a lysozyme-dependent manner.

Crohn's disease (CD) is a complex and poorly understood myeloid-mediated disorder. Genetic variants with loss of function in the NOD2 gene confer an increased susceptibility to ileal CD. While Nod2 in myeloid cells may confer protection against T-cell mediated ileopathy, it remains unclear whether it may promote resolution of the inflamed colon. In this study, we evaluated the function of Nod2 in myeloid cells in a model of acute colitis and colitis-associated colon cancer (CAC). To ablate Nod2 specifically within the myeloid compartment, we generated LysMCre/+;Nod2fl/fl mice. The role of NOD2 was studied in a setting of Dextran Sodium Sulfate (DSS)-induced colitis and in azoxymethane (AOM)/DSS model. Clinical parameters were quantified by colonoscopy, histological, flow cytometry, and qRT-PCR analysis. Upon DSS colitis model, LysMCre/+;Nod2fl/fl mice lost less weight than control littermates and had less severe damage to the colonic epithelium. In the AOM/DSS model, endoscopic monitoring of tumor progression revealed a lowered number of adenomas within the colon of LysMCre/+;Nod2fl/fl mice, associated with less expression of Tgfb. Mechanistically, lysozyme M was required for the improved disease severity in mice with a defect of NOD2 in myeloid cells. Our results indicate that loss of Nod2 signaling in myeloid cells aids in the tissue repair of the inflamed large intestine through lysozyme secretion by myeloid cells. These results may pave the way to design new therapeutics to limit the inflammatory and tumorigenic functions of NOD2.

Could red and near-infrared emitting fabric technology improve the severity of psoriasis, polymorphous light eruption, and alopecia areata?

AimLow-level light therapy (LLLT) may offer an adjunctive therapeutic tool for inflammatory skin conditions. This pilot study assessed the efficacy of a red/near-infrared (NIR)-emitting fabric for psoriasis, polymorphous light eruption (PMLE), and alopecia areata (AA).MethodsFourteen patients (five with psoriasis, five with PMLE, and four with AA) were instructed to wear a red/NIR-emitting (Lumiton®) garment during the 12-week study. Efficacy was assessed subjectively by patient-reported improvement and objectively by the redness, thickness, and scale of elbow psoriasis plaques, the frequency of PMLE flares, and the Severity of Alopecia Tool (SALT) score.ResultsThree patients with psoriasis completed the study while two self-discontinued. The three patients who completed the study noted improvement and two had improvements in lesion redness, thickness, or scale, while one was clinically stable. Three patients with PMLE completed the study, and none had a disease flare during the study period. Three patients with AA completed the study: two reported disease improvement and all three had an improved SALT score.ConclusionUse of a wellness apparel that emits red and NIR light may be associated with improved disease severity in patients with mild elbow psoriasis, PMLE, and limited AA. Limitations of this study include continuation on topical, intralesional, or systemic medications and small sample size.

E33 Identifying and understanding JDM in Africa: a survey of rheumatology care providers from Africa

Abstract Background It is estimated that millions of children in Africa suffer from pediatric rheumatic diseases (PRD). Despite this, as of 2021, there were just 28 pediatric rheumatologists in only 10 of the 54 African countries. With ∼700 million children living in Africa, this number falls far short of the recommended minimum 1750 pediatric rheumatologists needed for ideal care. Rheumatic and musculoskeletal diseases are the second leading cause of disability globally. However, there is a paucity of data on PRD in low and middle-income countries (LMIC) due to limited diagnostic capacities, scarcity of pediatric rheumatologists, and limited awareness of PRD. We have much to learn about the prevalence of PRD as well as clinical manifestations, optimal treatments, and outcomes in African children with PRD. Juvenile dermatomyositis (JDM) can cause significant morbidity and irreversible damage when inadequately treated, resulting in medical, social, and economic burden on patients, families, and healthcare systems, particularly in LMIC. The few studies of JDM in Africa suggest high rates of severe manifestations, including calcinosis, vasculitis, and pulmonary involvement. The objective of this survey is to better understand the scope of JDM burden in Africa by obtaining an overview of JDM and comparing this to data in previously published work. Methods A survey was distributed to members of the African League of Associations for Rheumatology (AFLAR; n = 233) and Paediatric Society of the African League Against Rheumatism (PAFLAR; n = 130) via WhatsApp groups. Respondents were queried about the total number of JDM patients seen currently or within the last 10 years; morbidities and clinical outcomes, including calcinosis, interstitial lung disease (ILD), clinically inactive disease, remission, and death; and availability and accessibility of diagnostic tools and medications. Results A total of 43 (12%) individuals started the survey, with 4 (9%) partially and 16 (37%) fully completing it, describing 216 JDM patients. One general pediatrician participated; the remainder were adult (n = 10; 50%), pediatric (n = 7; 35%), or adult/pediatric (n = 2; 10%) rheumatologists. Respondents represented the 5 regions of Africa, primarily Northern Africa (n = 12; 60%). Mortality was reported at 14% and 29% in Kenya and Zambia, respectively (Table 1). Many respondents identified limited availability of medications (56%), unfamiliarity with JDM by caregivers (69%) and other medical providers (44%), and delayed presentation to care (75%). Access and/or cost limited use of diagnostic tools and medications. Of the 27 queried diagnostic tools and medications, 13 were reported to be accessible to only 50% or fewer of respondents, the majority (69%) of whom were from Northern or Southern African countries. Despite the lack of cost or other apparent access barriers, disease assessment tools are used by only 53% of respondents. Conclusion This is the first study to explore JDM on a broad scale across the African continent. We identified 216 African children with JDM within the past 10 years, exceeding the previously published reports of 196 JDM patients seen in the last 25 years and likely still underestimating prevalence. Our results suggest substantially higher rates of severe disease, with mortality rates in some countries vastly different from the 1–3% reported in high-income countries. Many respondents were limited in their capacity to diagnose and treat JDM, but there was a wide range across African regions that seemed to parallel known disparities in healthcare resource availability in Africa. This survey highlighted important possible differences in disease manifestations and outcomes that warrant further study. Future collaboration with our African colleagues is critical to raise awareness of JDM to ultimately improve disease severity and outcomes. Ethics Institutional review board approval was obtained with waiver of informed consent.

GIRUS-net: A Multimodal Deep Learning Model Identifying Imaging and Genetic Biomarkers Linked to Alzheimer's Disease Severity.

We introduce an explainable deep neural architecture that combines brain structure with genetic influence to improve disease severity prediction in Alzheimer's disease. Our framework consists of an encoder, a decoder, and a rank-consistent ordinal regression module. The encoder projects neural imaging and genetics data into a low-dimensional latent space regularized by the decoder. The ordinal regression module guides the feature embedding process to find discriminative patterns representative of disease severity. We also add a learnable dropout layer that learns feature importance and extracts explainable biomarkers from the data. We evaluate our model using structural MRI (sMRI) and Single Nucleotide Polymorphism (SNP) data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. In 2-class severity classification comparison, our model has a median F-score of 0.86 (baseline median F-score range: 0.57-0.81). In 3-class classification comparison, our model's median F-score is 0.50 (baseline range: 0.17 - 0.41). In 4-class classification comparison, our model's median F-score is 0.40 (baseline range: 0.14 - 0.39). We demonstrate that our model provides improved disease diagnosis alongside sparse and clinically relevant biomarkers.Clinical relevance-This study provides a deep-learning model that can predict Alzheimer's disease severity levels while identifying consistent and clinically relevant biomarkers.

Blockade of IL-18 signaling downregulates homing of effector CD4+ T cells to the gut mucosa and provides protection from experimental IBD

Abstract The immunological complexity of inflammatory bowel disease (IBD) results in persistent intestinal inflammation in millions of patients. As an epithelial cell-derived cytokine essential in the differentiation of CD4+ T helper cells, interleukin 18 (IL-18) is emerging as a therapeutic target for IBD. When naïve CD4+ T cells are stimulated with IL-18, the production of IFNγ and differentiation of Th1 cells increase. IL18R1−/− CD4+ T cells produce less IFNγ and inflammatory cytokines compared to WT. To examine the viability of targeting IL-18 in vivo, colitis was induced in WT, IL18−/−, and IL18R1−/− mice by DSS. In both knockouts, lower proportions of IFNγ- and IL17-producing CD4+ T cells were observed in the colon along with lesser overall severity relative to WT. To further investigate, we examined the interplay of antigen presenting cells and CD4+ T cells in vitro. IL18R1−/− Th1 cells had decreased α4β7 and GPR15 expression when co-cultured with WT BMDCs. Meanwhile, IL18R1−/− Tregs had decreased IFNγ and CCR9 expression when co-cultured with WT BMDCs that were stimulated with LPS and retinoic acid, suggesting that IL-18 may play a role in the differential gut homing of CD4+ T cell subsets. When CD4+ T cells are transferred to Rag2−/−, mice receiving IL18R1−/− T cells possess significantly lower proportions of α4β7+ Th1 cells while the proportion of Tregs in the colon are increased. Treatment of mice with DSS or Mdr1a−/− colitis with an oral IL-18 inhibitor (20 mg/kg) resulted in decreased Th1 cells and neutrophils, lower histological scores and improved disease severity. From converging data, we deduce that inhibition of IL-18 may alleviate exacerbated immune responses associated with IBD, yielding a favorable therapeutic.

Trend in the admissions of patients with non-COVID-19 respiratory symptoms during COVID-19 pandemic and its impact on hospital finances in Surabaya, Indonesia

BackgroundCOVID-19 cases surge, it has a crucial impact on healthcare systems, with rapidly increasing demand for healthcare resources in hospitals and intensive care units (ICUs) in Indonesia and worldwide. It is necessary to quantify the extent to which the effects of the COVID-19 pandemic on the hospital admissions, and clinical and financial outcomes of patients with non-COVID-19 respiratory symptoms. ObjectiveTo determine whether the COVID-19 pandemic changed the hospitalisation of child and adult patients with non-COVID-19 respiratory conditions and whether these changes affected the patient's disease condition, clinical outcomes, and hospital finances. MethodsA retrospective cohort study was conducted from May 1, 2018 (before the COVID-19 pandemic) until December 31, 2021. Total sampling was done to compare hospital admission of patients with non-COVID-19 respiratory symptoms before versus during the COVID-19 pandemic. The results were analyzed using SPSS 26.0 and SmartPLS.v.3.2.9. ResultsThere was a reduction in hospitalisations for respiratory disorders unrelated to COVID-19 during the pandemic by 55.3% in children and 47.8% in adult patients. During the pandemic, the average hospital revenue per patient of child and adult patients increased significantly, but the profit per patient decreased. Pathway analysis showed that in children, the COVID-19 Pandemic changed disease severity and complexity (β = 0.132, P < 0.001), as well as clinical outcomes (β = 0.029, P < 0.05). In adults, the COVID-19 pandemic improves disease severity and complexity (β = -0.020, P < 0.001), as well as clinical outcomes (β = −0.013, P < 0.001). COVID-19 pandemic increases care charges (in children with β = 0.135, P < 0.001; and in the adult patients with β = 0.110, P < 0.001), worsens hospital financial outcomes relating to child (β = −0.093, P < 0.001) and adult patient (β = −0.073, P < 0.001). In adult patients, seasonal variations moderate the impact of the COVID-19 pandemic on improving disease conditions (β = −0.032, P=<0.001). The child structural model effectively predicted clinical outcomes (Q2 = 0.215) and financial outcomes (Q2 = 0.462). The adult structural model effectively predicted clinical outcomes (Q2 = 0.06) and financial outcomes (Q2 = 0.472). ConclusionThe conclusions are that the number of non-COVID respiratory patients decreased during the COVID-19 pandemic (47.8% in adult patients, 55.3% in child patients). Disease severity and complexity increased in child patients but decreased in adult patient. Costs of care and insurance payments increased. Since the insurance payments did not increase as much as the cost of care, hospital profit decreased.

A Comparison of Topical Corticosteroids and Topical Calcineurin Inhibitors for the Treatment of Atopic Dermatitis

Topical corticosteroids (TCS) are a mainstay of treatment for atopic dermatitis (AD). There are shared physician and patient concerns that TCS use can result in skin atrophy and systemic absorption. The clinical use of topical calcineurin inhibitors (TCI) for AD is relatively limited despite evidence that TCI are safe and effective. Understanding the differences in efficacy and adverse effects between TCS and TCI can help shape prescription practices to the benefit of patients. The objective of this review is to characterize the difference in efficacy and adverse effects between TCS and TCI. A review of the literature between 2002 and 2022 was performed using the PubMed, EMBASE, and Cochrane Library databases. Ten studies comparing TCS of varying potencies with TCI approved for AD treatment were included in the review. Outcome measures were qualified using percent reductions on the modified Eczema Area and Severity Index score and decreases in physician's global evaluation of AD severity. Tacrolimus had statistically significant (P < .05) improvement in disease severity compared with TCS in 4 of the 5 studies that compared against weak TCS. The data suggest greater treatment efficacy of tacrolimus over weak TCS, and inferior performance of pimecrolimus (TCI) compared with both tacrolimus and weak TCS. It is difficult to draw conclusions between moderate, potent, and very potent TCS and TCI due to the small number of studies making comparisons. TCI can improve disease severity, especially on thin or intertriginous skin regions most vulnerable to adverse events with TCS treatment, and their use may help overcome adherence issues due to patient bias against TCS.