A nomogram based on clinical factors and CT radiomics for predicting anti-MDA5+ DM complicated by RP-ILD.

OBJECTIVES: Anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) DM complicated by rapidly progressive interstitial lung disease (RP-ILD) has a high incidence and poor prognosis. The objective of this study was to establish a model for the prediction and early diagnosis of anti-MDA5+ DM-associated RP-ILD based on clinical manifestations and imaging features. METHODS: A total of 103 patients with anti-MDA5+ DM were included. The patients were randomly split into training and testing sets of 72 and 31 patients, respectively. After image analysis, we collected clinical, imaging and radiomics features from each patient. Feature selection was performed first with the minimum redundancy and maximum relevance algorithm and then with the best subset selection method. The final remaining features comprised the radscore. A clinical model and imaging model were then constructed with the selected independent risk factors for the prediction of non-RP-ILD and RP-ILD. We also combined these models in different ways and compared their predictive abilities. A nomogram was also established. The predictive performances of the models were assessed based on receiver operating characteristics curves, calibration curves, discriminability and clinical utility. RESULTS: The analyses showed that two clinical factors, dyspnoea (P = 0.000) and duration of illness in months (P = 0.001), and three radiomics features (P = 0.001, 0.044 and 0.008, separately) were independent predictors of non-RP-ILD and RP-ILD. However, no imaging features were significantly different between the two groups. The radiomics model built with the three radiomics features performed worse than the clinical model and showed areas under the curve (AUCs) of 0.805 and 0.754 in the training and test sets, respectively. The clinical model demonstrated a good predictive ability for RP-ILD in MDA5+ DM patients, with an AUC, sensitivity, specificity and accuracy of 0.954, 0.931, 0.837 and 0.847 in the training set and 0.890, 0.875, 0.800 and 0.774 in the testing set, respectively. The combination model built with clinical and radiomics features performed slightly better than the clinical model, with an AUC, sensitivity, specificity and accuracy of 0.994, 0.966, 0.977 and 0.931 in the training set and 0.890, 0.812, 1.000 and 0.839 in the testing set, respectively. The calibration curve and decision curve analyses showed satisfactory consistency and clinical utility of the nomogram. CONCLUSION: Our results suggest that the combination model built with clinical and radiomics features could reliably predict the occurrence of RP-ILD in MDA5+ DM patients.

Interplay between COVID-19 and Secukinumab treatment in Spondylarthritis patients during the omicron surge: a retrospective cohort study.

The objective of this retrospective cohort study was to assess the relationship between Corona Disease 2019 (COVID-19) and Secukinumab treatment in patients with Spondylarthritis (SpA) in China during the omicron surge. Researchers retrieved 1018 medical records of Secukinumab-treated patients between January 2020 and January 2023 from the West China Hospital of Sichuan University. Out of these, 190 SpA patients from the rheumatology clinic were selected for the study. Guided phone questionnaires were administered by research staff to collect baseline characteristics, SpA disease status, and COVID-19 clinical outcomes. Cohabitants served as the control group and provided COVID-19 related data. Of the 190 potential SpA patients, 122 (66%) completed the questionnaire via phone, along with 259 cohabitants. 84.4% of SpA patients were diagnosed with Ankylosing Spondylitis (AS), and 15.6% were diagnosed with Psoriatic Arthritis (PsA). The rate of SARS-CoV-2 infection was 83.6% in the Secukinumab group and 88.8% in the cohabitants control group, with no significant difference (OR = 0.684, CI 0.366-1.275). One instance of severe COVID-19 was observed in the Secukinumab group, while two were identified in the cohabitants control group. Patients in the Secukinumab group had less time with fever caused by COVID-19 (p = 0.004). Discontinuing Secukinumab after SARS-CoV-2 infection did not significantly affect the course of COVID-19 or worsen SpA status according to our data. Our study suggests that administering Secukinumab to SpA patients does not increase their susceptibility to contracting SARS-CoV-2, and may have a positive effect on the course of SARS-CoV-2 infection.

COVID-19 in Systemic Lupus Erythematosus patients treated with belimumab: a retrospective clinical study.

BACKGROUND: Routine use of immunosuppressive agents in systemic lupus erythematosus (SLE) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) potentially increases the risk of adverse outcomes. belimumab, a monoclonal antibody for the treatment of SLE, remains untested for its specific impact on coronavirus disease 2019 (COVID-19) symptoms in these patients. Here, this research investigated the effect of belimumab on COVID-19 symptoms in SLE patients infected with SARS-CoV-2. METHODS: This study enrolled SLE patients who underwent treatment with belimumab. After thorough screening based on the inclusion and exclusion criteria, data pertaining to COVID-19 for both the participants and their cohabitants were obtained through telephone follow-up. The potential impact of belimumab on COVID-19 was evaluated by comparing COVID-19 symptoms and medication use across various groups to investigate the association between belimumab treatment and COVID-19 in SLE. RESULTS: This study involved 123 SLE patients, of whom 89.4% tested positive for SARS-CoV-2. Among cohabitants of SLE patients, the SARS-CoV-2 positive rate was 87.2% (p = 0.543). Patients treated with belimumab exhibited a lower incidence of multiple COVID-19 symptoms than their cohabitating counterparts (p < 0.001). This protective effect was found to be partially related to the time of last belimumab administration. Among those with COVID-19, 30 patients opted to discontinue their anti-SLE drugs, and among them, 53% chose to discontinue belimumab. Discontinuing drugs did not increase the risk of hospitalization due to SARS-CoV-2 infection. CONCLUSION: This study concluded that treatment with belimumab did not increase susceptibility to COVID-19 and beneficially alleviated the symptoms of COVID-19.

Gut microbiota dysbiosis characterized by abnormal elevation of Lactobacillus in patients with immune-mediated necrotizing myopathy.

Aim: The gut microbiota plays an important role in human health. In this study, we aimed to investigate whether and how gut microbiota communities are altered in patients with immune-mediated necrotizing myopathy (IMNM) and provide new ideas to further explore the pathogenesis of IMNM or screen for its clinical therapeutic targets in the future. Methods: The gut microbiota collected from 19 IMNM patients and 23 healthy controls (HCs) were examined by using 16S rRNA gene sequencing. Alpha and beta-diversity analyses were applied to examine the bacterial diversity and community structure. Welch's t test was performed to identify the significantly abundant taxa of bacteria between the two groups. Spearman correlation analysis was performed to analyze the correlation between gut microbiota and clinical indicators. A receiver operator characteristic (ROC) curve was used to reflect the sensitivity and specificity of microbial biomarker prediction of IMNM disease. P < 0.05 was considered statistically significant. Results: Nineteen IMNM patients and 23 HCs were included in the analysis. Among IMNM patients, 94.74% (18/19) of them used glucocorticoids, while 57.89% (11/19) of them used disease-modifying antirheumatic drugs (DMARDs), and the disease was accessed by MITAX (18.26 ± 8.62) and MYOACT (20.68 ± 8.65) scores. Participants in the groups were matched for gender and age. The diversity of the gut microbiota of IMNM patients differed and decreased compared to that of HCs (Chao1, Shannon, and Simpson indexes: p < 0.05). In IMNM patients, the relative abundances of Bacteroides, Roseburia, and Coprococcus were decreased, while that of Lactobacillus and Streptococcus were relatively increased. Furthermore, in IMNM patients, Lactobacillus was positively correlated with the levels of anti-signal recognition particle (SRP) antibodies, anti-Ro52 antibodies, and erythrocyte sedimentation rate (ESR), while Streptococcus was positively correlated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies and C-reactive protein (CRP). Roseburia was negatively correlated with myoglobin (MYO), cardiac troponin T (cTnT), ESR, CRP, and the occurrence of interstitial lung disease (ILD). Bacteroides was negatively correlated with ESR and CRP, and Coprococcus was negatively correlated with ESR. Finally, the prediction model was built using the top five differential genera, which was verified using a ROC curve (area under the curve (AUC): 87%, 95% confidence interval: 73%-100%). Conclusion: We observed a characteristic compositional change in the gut microbiota with an abnormal elevation of Lactobacillus in IMNM patients, which was accompanied by changes in clinical indicators. This suggests that gut microbiota dysbiosis occurs in IMNM patients and is correlated with systemic autoimmune features.

Proteomics: Potential techniques for discovering the pathogenesis of connective tissue diseases-interstitial lung disease.

Interstitial lung disease (ILD) is one of the most serious lung complications of connective tissue disease (CTD). The application of proteomics in the past decade has revealed that various proteins are involved in the pathogenesis of each subtype of CTD-ILD through different pathways, providing novel ideas to study pathological mechanisms and clinical biomarkers. On this basis, a multidimensional diagnosis or prediction model is established. This paper reviews the results of proteomic detection of different subtypes of CTD-ILD and discusses the role of some differentially expressed proteins in the development of pulmonary fibrosis and their potential clinical applications.

Effects of Microecological Regulators on Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials.

In this study, the available data from published randomized, controlled trials (RCTs) of the use of intestinal microecological regulators as adjuvant therapies to relieve the disease activity of rheumatoid arthritis (RA) are systematically compared. An English literature search was performed using PubMed, Embase, Scopus, Web of Science and the Cochrane Central Registry of Controlled Trials and supplemented by hand searching reference lists. Three independent reviewers screened and assessed the quality of the studies. Among the 2355 citations identified, 12 RCTs were included. All data were pooled using a mean difference (MD) with a 95% CI. The disease activity score (DAS) showed a significant improvement following microecological regulators treatment (MD (95% CI) of -1.01 (-1.81, -0.2)). A borderline significant reduction in the health assessment questionnaire (HAQ) scores was observed (MD (95% CI) of -0.11 (-0.21, -0.02)). We also confirmed the known effects of probiotics on inflammatory parameters such as the C-reactive protein (CRP) (MD -1.78 (95% CI -2.90, -0.66)) and L-1ß (MD -7.26 (95% CI -13.03, -1.50)). No significant impact on visual analogue scale (VAS) of pain and erythrocyte sedimentation rate (ESR) reduction was observed. Intestinal microecological regulators supplementation could decrease RA activity with a significant effect on DAS28, HAQ and inflammatory cytokines. Nevertheless, these findings need further confirmation in large clinical studies with greater consideration of the confounding variables of age, disease duration, and individual medication regimens.

Starch-guest complexes interactions: Molecular mechanisms, effects on starch and functionality.

Starch is a natural, abundant, renewable and biodegradable plant-based polymer that exhibits a variety of functional properties, including the ability to thicken or gel solutions, form films and coatings, and act as encapsulation and delivery vehicles. In this review, we first describe the structure of starch molecules and discuss the mechanisms of their interactions with guest molecules. Then, the effects of starch-guest complexes on gelatinization, retrogradation, rheology and digestion of starch are discussed. Finally, the potential applications of starch-guest complexes in the food industry are highlighted. Starch-guest complexes are formed due to physical forces, especially hydrophobic interactions between non-polar guest molecules and the hydrophobic interiors of amylose helices, as well as hydrogen bonds between some guest molecules and starch. Gelatinization, retrogradation, rheology and digestion of starch-based materials are influenced by complex formation, which has important implications for the utilization of starch as a functional and nutritional ingredient in food products. Controlling these interactions can be used to create novel starch-based food materials with specific functions, such as texture modifiers, delivery systems, edible coatings and films, fat substitutes and blood glucose modulators.

Risk of Early Infection in Idiopathic Inflammatory Myopathies: Cluster Analysis Based on Clinical Features and Biomarkers.

Patients with idiopathic inflammatory myopathies (IIMs), referred to as myositis, are prone to infectious complications, which hinder the treatment of the disease and worsen the outcome of patients. The purpose of this study was to explore the different types of infectious complications in patients with myositis and to determine the predisposing factors for clinical reference. A retrospective study was conducted on 66 patients with IIM who were divided into different subpopulations by an unsupervised analysis of their clinical manifestations, laboratory features, and autoantibody characteristics. Combined with the incidence of infectious complications, the types of infectious pathogens and the sites of infection, the characteristics of infection, and susceptibility factors were explored. Three clusters with significantly different clinical characteristics and coinfection rates were identified (76.2% vs. 41.6% vs. 36.4%, p = 0.0139). Cluster 1 (n = 12) had a moderate risk of infection, with an infection rate of 41.6%. The patients in cluster 1 had a high probability of positive mechanic's hands, periungual erythema, anti-Ro52 antibody, and anti-Jo1 antibody. CD3 and CD4 were the highest among the three groups. Cluster 2 (n = 21) had a high risk of infection, and the incidence of infection was 76.2%. Almost all patients in this cluster had a rash, prominent clinical symptoms, and decreased WBC, PMN, LYM, CD3, and CD4 counts. Cluster 3 (n = 33) had a low risk of infection, with an infection rate of 36.4%. Compared with the other two clusters, cluster 3 (n = 33) lacked a typical rash but had a high ANA-positive rate. The patients in cluster 1 and cluster 3 were mainly infected by viruses, followed by bacterial infections. In cluster 2 patients, bacterial infections were the most prevalent. Fungal and Pneumocystis carinii were common causes of cluster 2 and 3 infections. In addition, the patients within a cluster often have a single infection, and pulmonary infections are the most common. We clustered the patients with IIM complicated with infection into three different types by their clinical symptoms and found that there were differences in the infection risk and infection types among the different cluster groups.

Progress in the treatment of urethral adenocarcinoma.

BACKGROUND: Urothelial adenocarcinoma (UA) is a rare subtype of primary urothelial carcinoma, which is more common in women and has a poor prognosis. Because of their low incidence, most of the existing literature is based on case reports and there is a lack of comprehensive literature on this type of tumor. PURPOSE: This article provides a comprehensive and systematic review of the epidemiology, pathological types, treatment, and prognosis of UA. Especially in the treatment section, we reviewed the various treatment methods including surgery, radiotherapy, chemotherapy, immunotherapy and molecular targeted therapy. This review aims to provide a theoretical basis for the clinical diagnosis and management of UA. METHODS: We reviewed the relevant literature of UA from Pubmed. CONCLUSION: There is no standard treatment for UA. Multidisciplinary therapy, including surgery, radiotherapy and chemotherapy, is the current trend. Immunotherapy and molecular targeted therapy will also become viable options for the treatment of UA in future.

Decreased Th1 Cells and Increased Th2 Cells in Peripheral Blood Are Associated with Idiopathic Inflammatory Myopathies Patients with Interstitial Lung Disease.

Interstitial lung disease (ILD) is a highly fatal manifestation of idiopathic inflammatory myopathies (IIMs). Th cells play important roles in the initiation of ILD. Here, we investigated the clinical significance of peripheral blood Th cells in IIMs-ILD patients. Eleven healthy controls (HC) and 53 patients diagnosed with IIMs were included, including 30 with ILD (IIMs-ILD) and 23 without ILD (IIMs-non-ILD). Circulating Th1, Th2, Th17, and Treg cells were examined by flow cytometry, and their correlation with clinical and laboratory findings was analyzed by Spearman's correlation and logistic regression. The proportion of Th1 cells decreased and Th2 cells increased in IIMs-ILD compared with IIMs-non-ILD (median (quartile): 2.99 (1.59-5.39) vs. 6.91 (3.48-10.04), p < 0.001; 2.67 (1.79-4.67) vs. 1.62 (0.85-2.66), p = 0.006) and correlated with disease activity. The Th1-cell proportion decreased in anti-MDA5 antibody-positive patients, while the Th2 cell proportion increased in patients with nonspecific interstitial pneumonia compared with IIMs-non-ILD (2.66 (1.06-4.35) vs. 6.91 (3.48-10.04), p = 0.002; 3.09 (2.03-5.72) vs. 1.62 (0.85-2.66), p = 0.016). Univariate analysis showed that a lower Th1 proportion, higher Th2 proportion increased, lower CK level, positivity for ARS, or anti-Ro52 antibodies (OR = 0.7122; OR = 1.679; OR = 0.9993; OR = 9.188; and OR = 6.161, respectively) were associated with the occurrence of ILD in IIMs patients. Decreased Th1 cells and elevated Th2 cells in peripheral blood may be involved in the pathogenesis of ILD in IIMs patients and have different effects on different serological and imaging subtypes.

Gut microbiome and metabolites: The potential key roles in pulmonary fibrosis.

There are a wide variety of microbiomes in the human body, most of which exist in the gastrointestinal tract. Microbiomes and metabolites interact with the host to influence health. Rapid progress has been made in the study of its relationship with abenteric organs, especially lung diseases, and the concept the of "gut-lung axis" has emerged. In recent years, with the in-depth study of the "gut-lung axis," it has been found that changes of the gut microbiome and metabolites are related to fibrotic interstitial lung disease. Understanding their effects on pulmonary fibrosis is expected to provide new possibilities for the prevention, diagnosis and even treatment of pulmonary fibrosis. In this review, we focused on fibrotic interstitial lung disease, summarized the changes the gut microbiome and several metabolites of the gut microbiome in different types of pulmonary fibrosis, and discussed their contributions to the occurrence and development of pulmonary fibrosis.

Immune checkpoint inhibitor in a case with primary urethral adenocarcinoma with lung metastasis.

Primary urethral adenocarcinoma is extremely rare, and the clinical experience in optimizing the management is limited. The efficacy of immune checkpoint inhibitors for these patients is not clear. Here, we describe a 52-year-old patient with primary urethral adenocarcinoma accompanied by inguinal lymph nodes and lung metastasis with progressive disease after radiotherapy and multiline chemotherapy. The expression of programmed cell death ligand-1 (PD-L1) was positive. Hence, this patient was treated with tislelizumab, an immune checkpoint inhibitor. The disease is well controlled and the overall survival time is 5 years. Moreover, the patient tolerated the treatment well. To our knowledge, this is the first reported case in which immunotherapy was used for primary urethral adenocarcinoma. The immune checkpoint inhibitors may be a novel option for the treatment of these patients.

Effectiveness of Urate-Lowering Therapy for Renal Function in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials.

Background and Objective: Hyperuricemia is closely related to chronic kidney disease (CKD). The effects of urate-lowering therapy (ULT) on renal outcomes are uncertain, and whether it is warranted in CKD patients is currently unclear. The aim of our meta-analysis of randomized clinical trials (RCTs) was to assess the effectiveness and safety of ULT for improving kidney function in patients with CKD. Methods: RCTs were retrieved from the PubMed, Embase, MEDLINE and Cochrane Central Register of Controlled Trials databases. The meta-analysis was performed using Review Manager and Stata/SE software. The outcomes were changes in renal function and serum uric acid (SUA), serum creatinine, and adverse events. Results: Twelve RCTs with 1,469 participants were included in the meta-analysis. ULT was found to effectively lower SUA (standard mean difference (SMD): -2.70; 95% confidence interval (CI): -3.71, -1.69) but the renoprotective effects were not superior to those of control therapy (placebo or usual therapy), which were stable in the subgroup analyses and sensitivity analyses. Regarding adverse events, their risks did not increase in the ULT group compared with the control group and were stable in the sensitivity analyses. Conclusion: The findings of our meta-analysis suggested that ULT can effectively lower SUA, but there is insufficient evidence to support the renoprotective effects of ULT in CKD patients. In addition, ULT is safe for patients with CKD. Systematic Review Registration: https://clinicaltrials.gov/, identifier PROSPERO (CRD42020200550).

Tailoring the properties of double-crosslinked emulsion gels using structural design principles: Physical characteristics, stability, and delivery of lycopene.

Lycopene is claimed to have numerous physiological benefits, but its poor water solubility, chemical instability, and low bioavailability limit its application in functional foods and health care products. In this study, lycopene-loaded emulsions containing oil droplets with different interfacial structures were prepared and then cross-linked using transglutaminase (TG) and/or calcium ions (Ca2+) to form emulsion gels. The oil droplets were first coated by interfacial layers comprised of whey protein isolate (WPI) and sodium alginate (SA). During emulsion preparation, the SA was added either before or after homogenization to create complex or layer-by-layer coatings, respectively. Subsequently, TG and Ca2+ were used to cross-link WPI and SA to form emulsion gels. The results show that double-crosslinking increased the gel strength and viscosity of the emulsion gels. The layer-by-layer emulsion gels were stronger and more viscous than the complex ones. The photochemical and gastrointestinal stability of lycopene encapsulated within the emulsion gels was higher than that of free lycopene. An MTT toxicity test showed that the emulsion gels exhibited no cytotoxicity to Caco-2 cells. The lycopene-loaded emulsion gels exhibited stronger anti-inflammatory activity on the Caco-2 cells than the control. In addition, the absorption of lycopene by the Caco-2 cells increased after encapsulation. This study provides a new approach of preparing edible soft materials to enhance the application of hydrophobic bioactives (like lycopene) in functional foods.

Effectiveness of Drug Treatments for Lowering Uric Acid on Renal Function in Patients With Chronic Kidney Disease and Hyperuricemia: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Hyperuricemia is very common in patients with chronic kidney disease (CKD); the role of hyperuricemia in the occurrence and progression of kidney disease remains an interesting and unresolved issue for nephrologists, and whether urate-lowering therapy (ULT) is warranted in CKD patients is still in controversy. To summarize and compare the clinical outcomes and adverse events (AEs) of three common ULT drugs, we performed a systematic review and network meta-analysis of randomized clinical trials (RCTs). Method: PubMed, MEDLINE, Clinical Trials.gov, EMBASE, and the Cochrane Central Register of Controlled Trials electronic databases were searched. The network meta-analysis was performed using the "gemtc 0.8-7" and its dependent packages in R software. The primary outcome was the change of renal function and uric acid; creatinine, proteinuria, blood pressure, and adverse events were assessed as the secondary outcomes. Results: 16 RCTs involving 1,943 patients were included in the final network analysis. Febuxostat, allopurinol, and benzbromarone were not found to exert superior effects over placebo upon renoprotective effect. With respect to lowering urate, the three drugs showed to be statistically superior to placebo, while febuxostat could better lower urate than allopurinol (MD: -1.547; 95% CrI: -2.473 to -0.626). It is also indicated that febuxostat was superior to placebo at controlling blood pressure, while no differences were observed when allopurinol and benzbromarone were compared to placebo. These results are stable in subgroup analysis. Conclusion: There is insufficient evidence to support the renoprotective effects of the three urate-lowering agents in CKD patients with hyperuricemia; febuxostat shows a tendency to be superior to allopurinol on lowering the decline of eGFR and increment of proteinturia, but the difference does not reach a statistical significance. Regarding its urate-lowering effect, febuxostat appears to be a satisfactory alternative to allopurinol and benzbromarone, and can control blood pressure better.