Systemic Inflammatory Disease Research Articles

Emerging Imaging Techniques for Atherosclerosis in Systemic Immune-Mediated Inflammatory Conditions.

Atherosclerosis affects patients with systemic immune-mediated inflammatory diseases at an increased rate compared with the general population. In recent years, our understanding of the pathophysiology of atherosclerosis has advanced considerably. Nevertheless, cardiovascular imaging modalities that can adequately assess the biological background of atherosclerosis have not reached widespread clinical adoption. Novel developments in cardiac imaging have the potential to enhance the diagnostic yield of these modalities further while providing essential insights into the anatomy, composition, and biology of atherosclerotic lesions. In this review, we highlight some of the latest developments in the field for the evaluation of atherosclerosis using advances in echocardiography, computed tomography, positron emission tomography, and cardiovascular magnetic resonance. Additionally, we discuss evidence specifically in patients with immune-mediated inflammatory diseases and outline unmet research needs for future development.

Association between advanced lung cancer inflammation index and unstable asthma: a population-based study from the NHANES 2007–2018

BackgroundAsthma exacerbation is associated with obesity and systemic inflammatory diseases, and advanced lung cancer inflammation index (ALI) is a novel biomarker of nutritional inflammation. The purpose of this study was to investigate the potential relationship between ALI and unstable asthma.MethodsThis cross-sectional study utilized data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Asthma was assessed through self-reported questionnaires. Multifactorial logistic regression, subgroup analyses, interaction assessments, smoothed curve fitting, and threshold effect analysis models were conducted to investigate the association between ALI and unstable asthma.ResultsThe study included 1,822 subjects with current asthma, and we found a linear positive association between ALI and unstable asthma, with higher levels of ALI significantly associated with an increased risk of asthma exacerbations in fully corrected models. However, the associations were not entirely consistent across subgroups. In subgroup analyses by body mass index (BMI) and race, unstable asthma and ALI were independently significant in the BMI (25–29.9) range and the Non-Hispanic White group. Interaction analysis suggested that BMI moderated the relationship between ALI and unstable asthma. Furthermore, smoothed curve fitting showed an inverted U-shaped relationship between log ALI and unstable asthma in subjects with a BMI <25 and male individuals, with inflection points observed at 1.53 and 2.13, respectively.ConclusionWe found a linear positive association between ALI and unstable asthma, which remained constant in the fully adjusted model. These findings suggest that higher levels of ALI were significantly associated with an increased risk of asthma exacerbation, particularly in asthmatic populations with BMI in the 25–29.9 range. However, more prospective studies are required to confirm our findings.

Identification of a 5-Plex Cytokine Signature that Differentiates Patients with Multiple Systemic Inflammatory Diseases.

Patients with non-infectious systemic inflammation may suffer from one of many diseases, including hyperinflammation (HI), autoinflammatory disorders (AID), and systemic autoimmune disease (AI). Despite their clinical overlap, the pathophysiology and patient management differ between these disorders. We aimed to investigate blood biomarkers able to discriminate between patient groups. We included 44 patients with active clinical and/or genetic systemic inflammatory disease (9 HI, 27 AID, 8 systemic AI) and 16 healthy controls. We quantified 55 serum proteins and combined multiple machine learning algorithms to identify five proteins (CCL26, CXCL10, ICAM-1, IL-27, and SAA) that maximally separated patient groups. High ICAM-1 was associated with HI. AID was characterized by an increase in SAA and decrease in CXCL10 levels. A trend for higher CXCL10 and statistically lower SAA was observed in patients with systemic AI. Principal component analysis and unsupervised hierarchical clustering confirmed separation of disease groups. Logistic regression modelling revealed a high statistical significance for HI (P = 0.001), AID, and systemic AI (P < 0.0001). Predictive accuracy was excellent for systemic AI (AUC 0.94) and AID (0.91) and good for HI (0.81). Further research is needed to validate findings in a larger prospective cohort. Results will contribute to a better understanding of the pathophysiology of systemic inflammatory disorders and can improve diagnosis and patient management.

The economic burden of diagnostic uncertainty on rare disease patients.

It often takes a long time before a rare disease is diagnosed. Without a diagnosis, the right therapy often cannot be carried out and without the right therapy, the patients are denied the opportunity for a cure or relief from their symptoms. In addition, rare diseases can also have economic consequences for those affected. This study aimed to investigate the extent to which a rare disease affects the income and work performance of the patients concerned and whether the use of AI in diagnostics would have the potential to reduce economic losses. The work performance and income of 71 patients of the outpatient clinic for rare inflammatory systemic diseases with renal involvement at Hannover Medical School were analyzed during the course of the disease. The WHO Health and Work Performance Questionnaire (HPQ) was used to collect data. During the patient interviews, the questionnaire was completed four times: at the onset of the first symptoms, when a diagnostic decision support system (DDSS) would have suggested the correct diagnosis, at the time of diagnosis and at the current status. With the onset of the diagnostic odyssey, the monthly net income of the patients under study dropped by an average of 5.32% due to lower work performance or work absenteeism. With the correct diagnosis, the original or even a better income of 11.92% could be achieved. Loss of income due to illness was more massive in patients with a rare disease with joint, muscle and connective tissue involvement than in patients with rare vasculitides. If a DDSS had been used, the loss of income would have been 2.66% instead of the actual 5.32%. Rare diseases resulted in temporary or existing income losses in 28.17% of the patients. Losses in work performance and income were related to the type of disease and were more pronounced in patients with joint, muscle or connective tissue disease than in patients with rare vasculitides. The use of a DDSS may have the potential to reduce the negative income effects of patients through earlier correct diagnosis. Retrospectively registered.

Relationship between Cardiometabolic index and endometriosis in a US nationally representative sample: results from NHANES 1999-2006

BackgroundEndometriosis is an estrogen-dependent gynecological endocrine condition and a systemic inflammatory disease associated to improper lipid metabolism and increased cardiovascular risk. The Cardiometabolic Index (CMI) is a novel indicator representing visceral adipose tissue distribution and metabolic dysfunction, integrating lipid metabolism indicators and the waist-to-height ratio. While anomalies in lipid metabolism are often associated with (BMI) Body Mass Index, literature consistently shows a negative link between endometriosis and female BMI, and some studies have found that endometriosis is one of the few reproductive diseases not persistently positively correlated with obesity. Given the limitations of BMI, a comprehensive index like CMI is crucial for exploring the incidence of endometriosis. Currently, research on the correlation between CMI and endometriosis is lacking, prompting this study to investigate this association.ObjectiveTo investigate the association between the CMI and the risk of having endometriosis in a sample representing the entire U.S. population.Study designA cross-sectional analysis was conducted using data from four cycles of the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2006. The study included individuals aged 20 to 54 with a documented history of endometriosis and complete CMI data. Logistic regression analysis, subgroup and interaction analyses, smooth curve fitting, and restricted cubic splines (RCS) were utilized to examine the association between CMI and endometriosis.ResultsThe study found that individuals with higher CMI had an increased probability of developing endometriosis. This relationship remained significant after adjusting for potential confounders such as age, ethnicity, Poverty Income Ratio (PIR), drinking, smoking, education level, and marital status. The fully adjusted model revealed a positive correlation between CMI and endometriosis (OR = 1.21; 95% CI, 1.04–1.40, p &amp;lt; 0.05). Subgroup and interaction analyses showed no significant effect modification by age, BMI, PIR, hypertension, drinking, smoking, or menarche age (all p-values for interaction &amp;gt; 0.05).ConclusionOur study shows a link between CMI and the chance of getting endometriosis.Due to the common occurrence of endometriosis and the lack of clarity surrounding their cause, more study is needed to confirm our results and find out if CMI could be used as a warning sign for endometriosis.

A systematic review of the implications of lipocalin-2 expression in periodontal disease.

Evidence suggests that lipocalin-2 (LCN-2), a bone-derived protein, is upregulated in periodontal diseases. This systematic review aimed to evaluate LCN-2 concentrations in individuals with periodontal diseases, identifying the most suitable body fluids for its detection, the type of periodontal disease with the highest LCN-2 expression, its association with other inflammatory markers and systemic diseases, and whether its expression can be modified by periodontal treatment. A systematic search of Google Scholar, PubMed, and ProQuest up to August 2024 was conducted. The studies were screened and selected by the authors according to specific eligibility criteria. Quality assessment of the included studies was performed according to the study type using STROBE statement for observational studies or the modified Jadad scale for experimental studies. The review was registered in PROSPERO (CRD42023458565). In total, three thousand six hundred and thirty-eight reports were identified, of which twenty-seven were full-text assessed for eligibility, including eleven articles. Seven articles were observational, and four were experimental. Significantly elevated LCN-2 levels were reported in patients with periodontal disease across 9 studies, being higher in periodontitis rather than gingivitis. LCN-2 was mainly detected in gingival crevicular fluid (GCF) and saliva. LCN-2 expression is related to the increment of inflammatory markers, and periodontal therapy decreases LCN-2 concentrations. LCN-2 levels were aggravated when periodontitis was accompanied by obesity and type 2 diabetes. LCN-2 is implicated in periodontal diseases, probably through the inflammation process.

EFFICACY OF HORMONAL METHODS AS ONE OF THE PILLARS IN THE TREATMENT OF ENDOMETRIOSIS

Endometriosis is a gynecological manifestation of a systemic inflammatory disease that causes chronic pelvic pain and can lead to infertility, characterized by the growth of endometrial tissue outside the uterus. This occurs due to retrograde menstruation, which consists of the leakage of part of the menstrual flow into the pelvis, and is common in 90% of women and eliminated by the immune system. However, in a portion of this population, the endometrial tissue proliferates and enters organs such as the intestine and bladder, growing during the menstrual period, which results in complications, intense pain and incapacity in daily life. It is estimated that between 5% and 10% of women of reproductive age worldwide are affected by this pathology, in addition to being the second most common pelvic disorder and the most frequent cause of female pelvic pain. Endometriosis is believed to be caused by the dysregulation of the female hormones estrogen and progesterone. Thus, the regulation of these hormonal agents through the use of hormonal methods has proven efficacy, as it reduces or even eliminates estrogenic stimulation and consequently improves the quality of life of patients; since this stimulus is the main agent responsible for the growth and permanence of the foci of this disease, which highlights the efficacy of this method as an important pillar in the treatment of endometriosis.

Endometriosis, Anxiety, and Atherosclerosis: A study of eight million young hospitalized women in United States.

In recent years, several studies have proposed an association between endometriosis and various cardiovascular diseases. Our study evaluated the association between endometriosis and atherosclerosis in patients under 35 years of age using a large population database. This was a retrospective population-based study. We used the data of more than eight million hospitalized women under 35 years of age who were registered in one of the hospitals participating in the Healthcare Cost and Utilization Project-National Inpatient Sample (HCUP NIS) during the study period of 2007 to 2014. The prevalence of endometriosis, atherosclerosis and related conditions was estimated, and logistic regression model was used to examine the association. In the period of study, we noted an upward pattern for the prevalence of atherosclerosis and a downward trend for endometriosis. Adjusting the analysis for sociodemographic characteristics and comorbidities, the probability of being diagnosed with atherosclerosis was 42% higher in patients with endometriosis (OR=1.421; 95%CI 1.058-1.910); 35% higher in patients with anxiety (OR=1.352; 95%CI 1.249-1.464); and 3 times higher in women with both endometriosis and anxiety (OR=3.075; 95%CI 1.969-4.803) compared to women without those conditions. In HCUP NIS databases some information such as the severity of disease, laboratory findings, or medical treatment is not available. The strong association between endometriosis and atherosclerosis suggests that they may share a similar mechanism possibly endothelial dysfunction related to chronic inflammation. Further studies on the potential role of psychologic conditions, such as anxiety, on systemic inflammatory diseases are also deemed timely and important.

Evaluation of Brain and Spinal Cord Lesions and Cerebrospinal Fluid Analysis in Detecting Demyelinating Diseases in Patients with Optic Neuritis

ABSTRACT Optic neuritis can be an early sign of demyelinating diseases like multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated diseases (MOGAD). We investigated the presence or absence of head and spinal cord lesions on magnetic resonance imaging (MRI) and assessed whether cerebrospinal fluid (CSF) tests are useful in detecting demyelinating disease in patients with first diagnosed optic neuritis. We conducted a retrospective study of 111 patients (47 idiopathic, 19 NMOSD, 16 MOGAD, 16 MS, 6 optic neuritis with cerebral lesions but that does not meet the McDonald’s criteria for MS (ON+)), and 7 chronic relapsing inflammatory optic neuropathy) diagnosed with optic neuritis without cerebral or spinal symptoms. Patients underwent evaluations including orbital, head, and spine MRI, along with CSF analysis. Among the 111 patients, 20 (35.1%: 4 NMOSD, 4 MOGAD, 7 MS, and 6 ON+) exhibited intracerebral or spinal cord lesions. Twelve patients showed findings on both orbital and head MRI, while six had no orbital MRI findings except for optic neuritis but exhibited lesions on head MRI. Five patients had spinal lesions without intracerebral lesions. CSF analysis revealed positive oligoclonal bands and elevated myelin basic protein levels indicate the high likelihood with systemic inflammatory demyelinating diseases. Even in the absence of concomitant encephalitis or myelitis symptoms or a history of these conditions, MRI images of patients with optic neuritis sometimes reveal lesions in the brain or spinal cord. CSF abnormalities were indicative of systemic demyelinating disease presence, extending beyond MS to NMOSD and MOGAD.

Sinulariolide Suppresses Inflammation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis and Mitigates Collagen-Induced Arthritis Symptoms in Mice.

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by active polyarthritis, which leads to functional loss and joint deformities. Natural compounds derived from marine organisms are considered valuable immune-modulating agents. This study aimed to assess the anti-inflammatory effect of sinulariolide, a soft coral-derived compound, on RA fibroblast-like synoviocytes and its therapeutic efficacy against collagen-induced arthritis (CIA). To determine the effects of sinulariolide on tumor necrosis factor-alpha (TNF-α)-induced inflammation, MH7A cells pre-treated with 10 ng/mL TNF-α for 24h were treated with sinulariolide. The effect of sinulariolide on proinflammatory cytokine expressions at both the mRNA and protein levels in the MH7A cells was assessed using real-time-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Further, we analyzed the effect of sinulariolide on the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways using Western blotting and the TransAM NF-κB p65 kit. To comprehensively evaluate the potential application of sinulariolide in the treatment of inflammatory diseases, we used a well-established collagen-induced arthritis (CIA) mouse model. We examined the tissue sections of the ankle joints of the mice, assessed synovial hyperplasia, inflammatory cell infiltration, and cartilage damage, and used ELISA to analyze changes in cytokine expression in the hind paw tissues. MH7A cells treated with sinulariolide showed a notable reduction in the expression of proinflammatory cytokines, which could be due to decreased activation of the MAPK and NF-kB pathways. Additionally, sinulariolide-treated mice showed significantly reduced joint swelling and lower clinical arthritis scores than those in the normal and control groups. Significant reductions in synovial hyperplasia, inflammatory cell infiltration, and cartilage damage were observed in the tissue sections of the ankle joints of the mice treated with sinulariolide. Furthermore, the expression of inflammatory cytokines in the hind paw tissue of the mice treated with sinulariolide was significantly decreased. Sinulariolide inhibited the progression of inflammation in MH7A cells. Sinulariolide treatment significantly reduced clinical arthritis symptoms and histological inflammatory responses in mice with CIA. Sinulariolide may serve as a potential therapeutic agent for RA.

Ameliorative Potency of Iridoid Glucoside Compound Catalpol on Inhibiting NF-κB-mediated Inflammation in Allergic Rhinitis-induced Mice

Background Over time, the prevalence of allergic rhinitis (AR) has surged due to various risk factors, notably attributed to global urbanization, rendering heightened levels of pollutants, including traffic-related emissions and particulate matter. About 25% of the global children population and 40% of the adult population were reported with AR. Even though AR is recognized as a systemic inflammatory disease, it often results in diverse other comorbidities, such as dermatitis, sinusitis, conjunctivitis, and otitis, requiring extensive and expensive treatment. Purpose We assessed the effectiveness of iridoid glucoside catalpol against AR in a mouse model. Catalpol is recommended in traditional Chinese medicine to treat diverse acute and chronic diseases. Methods AR was induced in mice with an ovalbumin-sensitized AR model and treated with 10 and 20 mg of catalpol. Nasal severity scoring was performed to confirm the AR induction in mice. Allergic mediators immunoglobulin E (IgE) and histamine were quantified in the serum to assess the anti-allergic response of catalpol. In nasal lavage fluid (NALF), the inflammatory mediators IgE Ab, prostaglandin D2, leukotriene C4, eosinophil cationic protein (ECP), and pro-inflammatory cytokines were measured to analyze the anti-inflammatory potency of catalpol. The binding capacity of nuclear factor-kappa B (NF-κB) to DNA was evaluated to assess the catalpol inhibitory potency against NF-κB-mediated inflammation in AR mice. To confirm the ameliorative potency of catalpol in AR mice, a histopathological analysis of nasal mucosa was performed. Results Catalpol treatment significantly decreased the nasal symptoms and reduced the allergic mediators in the serum of experimental animals. It effectively inhibited the synthesis of inflammatory mediators, ECP, and pro-inflammatory cytokines in the NALF, and also suppressed the NF-κB DNA-binding activity in AR mice. The decrease in ciliary loss, goblet cells, eosinophil infiltration, and vascular congestion observed with our nasal mucosa histopathological analysis confirmed the ameliorative potency of catalpol. Conclusion Our findings have proven catalpol inhibits NF-κB-mediated inflammatory response in AR mice. With further analysis, a potent natural compound, catalpol, can be formulated as a drug to treat AR.

Association between achieved cholesterol levels and the risk of major adverse cardiovascular events after acute coronary syndromes

Abstract Background European guidelines recommend reducing lipid levels to defined targets to lower cardiovascular risk after acute coronary syndromes (ACS). Purpose This study aims to evaluate the association of achieved and reduced lipid levels one year post-ACS with the risk of subsequent major adverse cardiovascular events (MACE) in a real-world setting. Methods Data from SPUM-ACS, a Swiss multicentric cohort of patients hospitalized with ACS between 2007 and 2021, were used to assess the association between lipid levels (LDL-C, non-HDL-C, HDL-C, triglycerides), relative difference from baseline lipid levels, and lipid targets achievement (LDL-C &amp;lt;1.8 and ≥50% reduction from baseline, non-HDL-C &amp;lt;2.2 and triglycerides &amp;lt;1.7mmol/l) one year after ACS with the risk of MACE (myocardial infarction, stroke, coronary revascularization, and cardiovascular death). The observation period for MACE started after a follow-up visit one year post-ACS, during which lipid levels were measured, extending over a median duration of 5.5 years. Cox proportional hazards models, adjusted age, sex, BMI, smoking status, statin therapy intensity, diabetes, systemic inflammatory disease, and creatinine were used. Predicted adjusted hazard ratios (HR) were represented graphically for continuous exposures. Analyses were repeated with interaction terms for predefined subgroups. Results 2579 ACS survivors (mean age 62 years; 80% male), primarily undergoing percutaneous revascularization, attended a follow-up visit one year after ACS and were followed up for a median of 5.5 years. 98% were prescribed statin therapy (59% high-intensity) at discharge. During the first year post-ACS, median LDL-C decreased from 3.7 to 2.4 mmol/l (-34%, p&amp;lt;0.001), non-HDL-C from 3.9 to 2.6 mmol/l (-32%, p&amp;lt;0.001), and triglycerides from 1.21 to 1.16 mmol/l (-6%, p&amp;lt;0.001); HDL-C increased from 1.1 to 1.2 mmol/l (+6%, p&amp;lt;0.001). 92% of patients were on statin therapy (50% high-intensity) one year after ACS. In log-linear models, one year after ACS, a 1 mmol/l reduction of LDL-C, non-HDL-C, and triglycerides levels to the target was associated with a lower risk of subsequent MACE by 23%, 24%, and 14%, respectively (p values &amp;lt;0.001). A 10% relative reduction from baseline levels of LDL-C, non-HDL-C and triglycerides was associated with a lower risk of MACE by 8%, 9%, and 4%, respectively (p values &amp;lt;0.001). Achieving LDL-C &amp;lt;1.8 mmol/l (21%, HR=0.71 [0.54, 0.93]), LDL-C reduction ≥50% from baseline (26%, HR=0.63 [0.48, 0.84]), non-HDL-C &amp;lt;2.2 mmol/l (30%, HR=0.65 [0.51, 0.83]), and triglycerides &amp;lt;1.7 mmol/l (76%, HR=0.76 [0.62, 0.94]) were all associated with a reduction in the risk of MACE. Neither age, sex, BMI, diabetes, or smoking status affected the results (p for interaction ≥0.05). Conclusion These findings affirm current recommendations and underscore lipid reduction and targets achievement as critical strategies for mitigating residual cardiovascular risk in patients with ACS.

Primary inflammatory disease in heart failure with preserved ejection fraction

Abstract Background Inflammation plays a fundamental role in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of underlying systemic inflammatory diseases represented by rheumatoid arthritis. Purpose This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and primary inflammatory diseases. Methods Consecutive patients undergoing hemodynamic exercise testing with concurrent expiratory gas analysis to evaluate dyspnea of unknown cause were identified. HFpEF was defined as left ventricular ejection fraction ≥50% and pulmonary capillary wedge pressure ≥15 mmHg (rest) or ≥25 mmHg (exercise). Patients with HFpEF were divided into groups with and without primary inflammatory diseases. Patients without inflammatory disease were divided into tertiles according to the value of C-reactive protein (CRP). Results Of 982 consecutively evaluated patients with HFpEF diagnosed (577 female, mean age 68 years), 79 (8%) had primary inflammatory disease. In multivariable logistic regression, female sex (OR 1.88; 95% CI 1.01-3.52), higher resting heart rate (OR 1.18; 95% CI 1.08-1.30), lower hemoglobin level (OR 0.84; 95% CI 0.70-0.99), absence of history of atrial fibrillation (OR 0.45; 95% CI 0.24-0.86) and absence of epicardial coronary artery disease (OR 0.45; 95% CI 0.22-0.93) were independently associated with inflammatory disease. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with inflammatory disease, reflected by lower arterial-venous oxygen content difference (Ca-vO2) at rest (4.2±0.7 mL/dL vs 4.6±1.0 mL/dL, P&amp;lt;.001) and during exercise (9.3±2.2 mL/dL vs 10.4±2.2 mL/dL, P&amp;lt;.001) (Figure 1A), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCO2 slope) was also more impaired (38.0±7.9 vs 36.2±7.3, P=.035). The HFpEF patients without inflammatory disease falling in the highest tertile of CRP) displayed lower Ca-vO2 during exercise, more closely resembling peripheral deficits observed in those with inflammatory disease (Figure 1B). During a median follow-up of 3.0 years, the composite outcome of all-cause deaths and HF hospitalization occurred in 127 patients (14%). Patients with HFpEF and inflammatory disease showed a higher incidence of composite outcome than those without (log-rank P=.030; Figure 2). Patients with inflammatory disease had higher risk of composite outcome compared to those without in adjusted analyses (HR 1.93; 95% CI 1.15-3.23), which was primarily attributable to higher risk of HF hospitalization (HR 2.85; 95% CI 1.08-7.52). Conclusion Patients with HFpEF and primary inflammatory disease have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared to those without.

Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies.

Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDMinclude targetingIFN-signaling (JAK, IFNAR1, IFN beta),B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA)including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.

Systemic Sweet Syndrome Recurrence in Lung Allograft: Autopsy Findings from First Reported Case

Abstract Introduction/Objective Sweet syndrome is a non-vasculitic neutrophilic dermatosis characterized by acute, neutrophilic inflammation, most classically in the skin. Sweet syndrome can, however, manifest with systemic organ involvement including the lungs. Pulmonary involvement by Sweet syndrome is exceedingly rare, and its recurrence in a pulmonary allograft is understudied. Methods/Case Report A 43-year-old female with a history of Sweet syndrome with pulmonary involvement developed chronic bronchiolitis obliterans requiring bilateral lung transplantation. Seven years after transplantation, the patient began exhibiting shortness of breath requiring hospitalization. During the patient’s hospital stay, cytomegalovirus viremia and SARS-CoV-2 positivity were detected, and new oral lesions were concerning for a Sweet syndrome flare. Her respiratory status continued to decline requiring escalating ventilatory support. An autopsy limited to the chest and abdomen was performed after she expired. The pleural cavities had extensive adhesions, and both lungs were heavy. Microscopically, the lungs showed extensive, intralumenal acute inflammation of the bronchi and bronchioles with marked chronic inflammation of the submucosa, histologically similar to the patient’s explanted lung specimen. There was also focal endogenous lipoid pneumonia due to bronchiolar obstruction. In addition to the inflammatory findings, multiple infectious agents were identified in the patient’s respiratory tract including SARS-CoV-2, cytomegalovirus, Epstein-Barr virus, Candida glabrata, Klebsiella pneumoniae, and Stenotrophomonas maltophilia. No underlying malignancy was identified. (This patient’s earlier course was reported previously: PMC8411443) Results (if a Case Study enter NA) NA Conclusion Pulmonary involvement in Sweet syndrome can cause significant morbidity, and prior to this case, allograft recurrence of Sweet syndrome had not previously been reported. For transplant patients with a history of pulmonary Sweet syndrome, recurrence should be considered in cases of allograft dysfunction. This case also highlights the importance of thorough microbiological studies in autopsies of patients with systemic inflammatory diseases being treated with extensive immunosuppressive therapies.

CTPAD: an interactive web application for comprehensive transcriptomic profiling in allergic diseases

BackgroundAllergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic diseases.ObjectiveThe aim of the study is to provide a comprehensive web tool for multiple analysis in allergic diseases.MethodsWe retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user feedback.ResultsWe developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution images.ConclusionsCTPAD largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://smuonco.shinyapps.io/CTPAD/.

Systemic Implications of Bullous Pemphigoid: Bridging Dermatology and Internal Medicine.

Background: Bullous pemphigoid is an autoimmune bullous disease that frequently affects a large skin surface area, but it can also present in localized areas. It has been hypothesized that bullous pemphigoid affects the systemic functioning of different organs because inflammatory cells and cytokines circulate throughout numerous organs. Results: Recent clinical and experimental studies have revealed an association between bullous pemphigoid and systemic organ disorders. To avoid the emergence of systemic organ diseases, the significance of systemic treatment in cases of severe bullous pemphigoid should be emphasized. Conclusions: Here, we discuss the specific molecular processes underlying typical systemic organ inflammatory diseases associated with bullous pemphigoids.

Intravenous Anakinra for Treating Macrophage Activation Syndrome in Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease characterized by fever, rash, arthritis, and multi-organ involvement. Macrophage activation syndrome (MAS), a serious complication of AOSD, poses significant diagnostic and therapeutic challenges. A 32-year-old male was diagnosed with AOSD in 2020 after being hospitalized for a fever of unknown origin and elevated liver enzymes. The patient was initially treated with corticosteroids and methotrexate but subsequently discontinued both treatment and follow-up. In September 2023, he presented with fever, sore throat, and elevated inflammatory markers. After screening for infections, methylprednisolone (MP) treatment was initiated because of AOSD activation. The following day, the patient was admitted to the intensive care unit due to an altered state of consciousness. Brain magnetic resonance imaging revealed brainstem involvement. Empirical treatments were initiated, including intravenous MP, and immunoglobulin therapy. Due to suspected macrophage activation syndrome (MAS), anakinra (ANA) infusion was initiated. Significant improvement was observed after the ANA infusion. This case highlights the complex management of severe AOSD complications, emphasizing the role of early recognition, aggressive therapy, and multidisciplinary care in improving outcomes. Macrophage activation syndrome (MAS) is a serious complication of adult-onset Still's disease characterized by systemic inflammation. Early recognition and prompt initiation of treatment are crucial due to the high mortality rate associated with MAS, especially when neurologic symptoms are present.Clinicians should not delay treatment pending confirmatory diagnostic tests when MAS is suspected, as early intervention can significantly impact patient outcomes.Anakinra, an interleukin-1 inhibitor, is typically administered subcutaneously but has shown promise when administered intravenously, particularly in severe cases of MAS.

Pathophysiology, Treatment, and Prognosis of Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome: A Review.

TAFRO syndrome, first reported in 2010, is a systemic inflammatory disease with a rapid onset and potentially fatal course if not treated promptly and appropriately. The name is derived from the initial letters describing the characteristic symptoms of thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly. It is sometimes considered a special subtype of idiopathic multicentric Castleman disease (iMCD) because lymph node biopsies often reveal the pathology findings seen in iMCD. However, its clinical manifestations and prognoses are not well documented. Since the clinical manifestations and prognoses of TAFRO syndrome differ significantly from those of iMCD, it is recognized as an independent disease concept and considered to partially overlap with the pathology of MCD. The pathogenesis of TAFRO syndrome remains largely unknown. Due to the lack of appropriate treatment, it often presents with multiple organ dysfunction and fatality. In this review, we summarized new findings on the pathogenesis of TAFRO syndrome and discussed current effective therapies and future treatment strategies.

Microplastics and Nanoplastics as Environmental Contaminants of Emerging Concern: Potential Hazards for Human Health

With nearly 40% of the total plastics produced being used for packaging, up to five trillion plastic bags are consumed in the world annually. The inadequate disposal of plastic waste and its persistence has become a serious challenge/risk to the environment, health, and well-being of living creatures, including humans. The natural degradation of plastics is extremely slow; large pieces of plastic may break down into microplastics (MPs) (1 μm–5 mm) or nanoplastics (NPs) (&lt;1000 nm) after protracted physical, chemical, and/or biological degradations. A brief overview of the transport of micro- and nanoplastics in the aquatic, terrestrial, and atmospheric environments is presented. Details are provided on the exposure routes for these waste materials and their entry into humans and other biota through ingestion, inhalation, and dermal contact. The greatest concern is the cumulative impact of the heterogeneous secondary MPs and NPs on planetary and human health. Inhaled MPs and NPs have been shown to affect the upper respiratory tract, lower respiratory tract, and alveoli; prolonged exposure can lead to chronic inflammatory changes and systemic disease. These can also lead to autoimmune diseases and other chronic health conditions, including atherosclerosis and malignancy. Sustainable mitigation strategies to reduce the impact of MPs/NPs include source reduction, material substitution, filtration and purification, transformation of plastic waste into value-added materials, technological innovations, etc. Multidisciplinary collaborations across the fields of medicine, public health, environmental science, economics, and policy are required to help limit the detrimental effects of widespread MPs and NPs in the environment.