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Abstract Background Anti-SS-A/Ro antibody (anti-SSA), the diagnostic marker of Sjögren’s syndrome (SS), is often detected in systemic sclerosis (SSc). Some patients are diagnosed with SSc/SS overlap syndromes, while there are anti-SSA-positive SSc cases without SS. In this study, we investigated the clinical characteristics of SSc with anti-SSA and clarified the clinical impact of this antibody in SSc. Methods A retrospective chart review was conducted of 156 patients with SSc at Yokohama City University Hospital from 2018 to 2021. Clinical data, laboratory data, imaging, and autoantibody positivity status were collected and analysed to assess the association between these variables and anti-SSA using multivariable logistic regression analysis. Results This cohort included 18 men and 138 women with SSc (median age, 69.0 years). Thirty-nine patients had diffuse cutaneous SSc (dcSSc) (25%), and 117 patients had limited cutaneous SSc (75%). Forty-four patients were anti-SSA-positive. Among them, 24 fulfilled the SS criteria. Multivariable logistic regression revealed that anti-SSA was statistically associated with interstitial lung disease (ILD; odds ratio [OR] = 2.67; 95% confidence interval [CI], 1.14–6.3; P = 0.024). Meanwhile, anti-SSA positivity tended to increase the development of digital ulcer (OR = 2.18; 95% CI, 0.99–4.82, P = 0.054). In the comparative analysis of the autoantibody single-positive and anti-SSA/SSc-specific autoantibody double-positive groups, the anti-SSA single-positive group showed a significantly increased risk of ILD (OR = 12.1; 95% CI, 2.13-140.57; P = 0.003). Furthermore, patients with SSc and anti-SSA indicated that anti-SSA-positive SSc without SS was strongly associated with dcSSc when compared to that in patients with SS (OR = 6.45; 95% CI, 1.23–32.60; P = 0.024). Conclusions Anti-SSA positivity increases the risk of organ involvement, such as ILD, in patients with SSc. Additionally, the anti-SSA-positive SSc without SS population may have more severe skin fibrosis than others. Anti-SSA may be a potential marker of ILD and skin severity in SSc.

Objective: The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection. Methods: This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months. Results: A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months. Conclusion: In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3- month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery of functional antibodies targeting G-protein-coupled receptors (GPCRs), whose presence has been demonstrated in different autoimmune conditions, has shed some light on SSc pathogenesis. These antibodies bind to GPCRs expressed on immune and non-immune cells as their endogenous ligands, exerting either a stimulatory or inhibitory effect on corresponding intracellular pathways. Growing evidence suggests that, in SSc, the presence of anti-GPCRs antibodies correlates with specific clinical manifestations. Autoantibodies targeting endothelin receptor type A (ETAR) and angiotensin type 1 receptor (AT1R) are associated with severe vasculopathic SSc-related manifestations, while anti-C-X-C motif chemokine receptors (CXCR) antibodies seem to be predictive of interstitial lung involvement; anti-muscarinic-3 acetylcholine receptor (M3R) antibodies have been found in patients with severe gastrointestinal involvement and anti-protease-activated receptor 1 (PAR1) antibodies have been detected in patients experiencing scleroderma renal crisis. This review aims to clarify the potential pathogenetic significance of GPCR-targeting autoantibodies in SSc, focusing on their associations with the different clinical manifestations of scleroderma. An extensive examination of functional autoimmunity targeting GPCRs might provide valuable insights into the underlying pathogenetic mechanisms of SSc, thus enabling the development of novel therapeutic strategies tailored to target GPCR-mediated pathways. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Lymphoproliferative diseases encompass a spectrum of heterogeneous conditions, necessitating a comprehensive understanding for effective management. This study aimed to analyze lymphoma subtypes, demographic variations, and their clinical implications. Introduction: The study focuses on a cohort of 57 subjects diagnosed with lymphoproliferative diseases between November 2008 and December 2011. The investigation aimed to characterize lymphoma subtypes, elucidate age-gender variations, and analyse organ and extra-nodal site involvements. Methodology: This retrospective study involved 57 subjects diagnosed with various lymphoproliferative diseases within a multi-specialty oncology hospital between November 2008 and December 2011. Detailed clinical records, including morphological, immune-phenotyping, and cytogenetic data, were meticulously reviewed and analysed. Morphological evaluations comprised peripheral blood and bone marrow smear analyses, stained with Leishman and May-Grunwald Giemsa stains, respectively. Immunophenotyping was conducted using a panel of monoclonal antibodies, and cytogenetic analyses involved short-term unstimulated cultures from fresh bone marrow aspirates, subjected to G-banding and Fluorescent In Situ Hybridization (FISH) assays. Results: Prominent findings included a notable prevalence of T cell non-Hodgkin lymphoma with lymph node involvement in younger individuals. Gender-based variations showcased diverse lymphoma subtypes in females across age brackets. Organ involvement analysis revealed distinct infiltrations in liver, spleen, and bone marrow, with extensive extra-nodal manifestations observed. Conclusion: The study's outcomes underscore the significance of personalized treatment strategies based on specific subtypes and demographic profiles. Clinical implications highlight the need for tailored diagnostic approaches and emphasize the importance of precise staging and disease monitoring for optimized patient care. [ABSTRACT FROM AUTHOR]

Abstract There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies. The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14th Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines. The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2–120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history. Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ‘ medical history and also through consulting with healthcare providers before vaccination.

There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies. The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14th Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines. The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2–120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history. Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to observe the demographic and clinical characteristics of immunoglobulin (Ig) G4–related disease (IgG4-RD). We aimed to compare different treatment methods and to identify the risk factors for non-response and relapse after treatment. Methods: We performed a retrospective study of 201 IgG4-RD patients initially diagnosed and treated at the First Affiliated Hospital of China Medical University from January 2016 to December 2020. Patients' sex, age, clinical manifestations, baseline biochemical values, the number of organs involved, and the type of organ involvement were recorded. All patients received glucocorticoid (GC) monotherapy or GC + immunosuppressant combination therapy. The serum IgG4 concentration as well as the details of clinical response, relapse, and side effects were recorded at 1, 3, 6, and 12 months after treatment. Results: The incidence of IgG4-RD was primarily centered in the age group of 50–70 years old, and the proportion of affected male patients increased with age. The most common clinical symptom was swollen glands or eyes (42.79%). The rates of single- and double-organ involvement were 34.83% and 46.27%, respectively. The pancreas (45.77%) was the most frequently involved organ in cases of single-organ involvement, and the pancreas and biliary tract (45.12%) was the most common organ combination in cases of double-organ involvement. Correlation analysis showed that the number of organs involved was positively related to the serum IgG4 concentration (r = 0.161). The effective rate of GC monotherapy was 91.82%, the recurrence rate was 31.46%, and the incidence of adverse reactions was 36.77%. Meanwhile, the effective rate of GC + immunosuppressant combination therapy was 88.52%, the recurrence rate was 19.61%, and the adverse reaction rate was 41.00%. There were no statistically significant differences in response, recurrence, and adverse reactions. The overall response rate within 12 months was 90.64%. Age (< 50 years old) and aorta involvement were significantly associated with non-response. The overall recurrence rate within 12 months was 26.90%. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement were significantly associated with recurrence. Conclusion: The clinical features vary among different age groups and according to gender. The number of organs involved in IgG4-RD is related to the serum IgG4 concentration. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement are risk factors for recurrence. [ABSTRACT FROM AUTHOR]

Abstract Background Serum biomarkers in the evaluation of organ involvement and prognostic monitoring of sarcoidosis have not been determined. The purpose of this study was to identify common biomarkers that could be used to assess organ involvement and monitor outcomes in sarcoidosis patients. Methods From Mar 2013 to Sep 2021, patients with newly diagnosed pulmonary sarcoidosis were enrolled in this study in Shanghai Pulmonary Hospital. The information from medical records was retrospectively collected including diagnosis, organ involvement, laboratory tests and follow up data. Differences of continuous variables between groups were analyzed by unpaired Student’s t-test. Multivariate logistic regression model was performed to identify potential independent factors associated with multiple organ involvement. Results A total of 832 patients were included in the study. There were 339 (40.7%) patients with single organ pulmonary involvement, while 493 (59.3%) patients had two to seven organs involved. Among the routine serum tests, only the serum angiotensin converting enzyme (SACE) level was an independent factor of multiple organ involvement. Compared to those patients without involvement, SACE levels were higher in patients with extra-thoracic lymph node, skin, or spleen involvement as well as abnormal calcium metabolism. Interleukin-2 receptor (IL-2R) levels were higher in patients with extra-thoracic lymph node, spleen involvement and abnormal calcium metabolism than in those without it. The mean levels of SACE and IL-2R showed upward trends paralleling the increase on number of organs involved. In follow up, SACE and IL-2R levels were both decreased in an improved patient group, while there was no obvious difference was noticed before and after treatment in patients with persistent disease. Conclusion SACE and IL-2R were useful as serum biomarkers in the initial evaluation of organ involvement as well as monitoring prognosis in sarcoidosis.

Background: Serum biomarkers in the evaluation of organ involvement and prognostic monitoring of sarcoidosis have not been determined. The purpose of this study was to identify common biomarkers that could be used to assess organ involvement and monitor outcomes in sarcoidosis patients. Methods: From Mar 2013 to Sep 2021, patients with newly diagnosed pulmonary sarcoidosis were enrolled in this study in Shanghai Pulmonary Hospital. The information from medical records was retrospectively collected including diagnosis, organ involvement, laboratory tests and follow up data. Differences of continuous variables between groups were analyzed by unpaired Student's t-test. Multivariate logistic regression model was performed to identify potential independent factors associated with multiple organ involvement. Results: A total of 832 patients were included in the study. There were 339 (40.7%) patients with single organ pulmonary involvement, while 493 (59.3%) patients had two to seven organs involved. Among the routine serum tests, only the serum angiotensin converting enzyme (SACE) level was an independent factor of multiple organ involvement. Compared to those patients without involvement, SACE levels were higher in patients with extra-thoracic lymph node, skin, or spleen involvement as well as abnormal calcium metabolism. Interleukin-2 receptor (IL-2R) levels were higher in patients with extra-thoracic lymph node, spleen involvement and abnormal calcium metabolism than in those without it. The mean levels of SACE and IL-2R showed upward trends paralleling the increase on number of organs involved. In follow up, SACE and IL-2R levels were both decreased in an improved patient group, while there was no obvious difference was noticed before and after treatment in patients with persistent disease. Conclusion: SACE and IL-2R were useful as serum biomarkers in the initial evaluation of organ involvement as well as monitoring prognosis in sarcoidosis. [ABSTRACT FROM AUTHOR]

Objective: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. Methods: In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. Results: Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1 pg/ml and 157.7 ± 88.7 pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = − 0.06, P = 0.632) and SLEDAI (r = − 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. Conclusions: Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis. [ABSTRACT FROM AUTHOR]

Abstract Background Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation.

Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery of functional antibodies targeting G-protein-coupled receptors (GPCRs), whose presence has been demonstrated in different autoimmune conditions, has shed some light on SSc pathogenesis. These antibodies bind to GPCRs expressed on immune and non-immune cells as their endogenous ligands, exerting either a stimulatory or inhibitory effect on corresponding intracellular pathways. Growing evidence suggests that, in SSc, the presence of anti-GPCRs antibodies correlates with specific clinical manifestations. Autoantibodies targeting endothelin receptor type A (ETAR) and angiotensin type 1 receptor (AT1R) are associated with severe vasculopathic SSc-related manifestations, while anti-C-X-C motif chemokine receptors (CXCR) antibodies seem to be predictive of interstitial lung involvement; anti-muscarinic-3 acetylcholine receptor (M3R) antibodies have been found in patients with severe gastrointestinal involvement and anti-protease-activated receptor 1 (PAR1) antibodies have been detected in patients experiencing scleroderma renal crisis. This review aims to clarify the potential pathogenetic significance of GPCR-targeting autoantibodies in SSc, focusing on their associations with the different clinical manifestations of scleroderma. An extensive examination of functional autoimmunity targeting GPCRs might provide valuable insights into the underlying pathogenetic mechanisms of SSc, thus enabling the development of novel therapeutic strategies tailored to target GPCR-mediated pathways.

Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. Objectives: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. Patients and methods: We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Results: Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. Conclusions: In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti–SS-A/Ro antibody positivity. [ABSTRACT FROM AUTHOR]

Copyright of Medizinische Klinik: Intensivmedizin & Notfallmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although anti-rheumatoid arthritis (RA) 33 antibodies have been reported to be present in various connective tissue diseases (CTDs), the clinical significance of anti-RA33 in CTDs is still obscure. This study was performed to explore the clinical significance of anti-RA33 in CTDs, especially systemic lupus erythematosus (SLE). A total of 565 patients with positive anti-nuclear antibodies who had been tested for anti-RA33 were included in this study and were further classified into RA33-positive and RA33-negative groups. The association between anti-RA33 and the clinical features of CTDs was examined. Receiver operating characteristic (ROC) analysis was performed to explore the diagnostic value of anti-RA33 in SLE and SLE-related organ involvement. The results showed that SLE was the most common disease in CTD patients positive for anti-RA33 (48.8%). Compared with the RA33-negative group, higher proportions of SLE-associated antibodies and SLE patients with a high disease activity as well as lower levels of serum complement components were observed in the RA33-positive group (all p < 0.05). Furthermore, CTD patients with positive anti-RA33 were more likely to suffer from mucocutaneous and hematological involvement as well as interstitial lung disease (all p < 0.05). ROC analysis revealed an area under the curve value of 0.634 (95% confidence interval: 0.587–0.681) for anti-RA33 in the diagnosis of SLE, with a specificity and sensitivity of 92.9% and 13.5%, respectively. Taken together, this study reveals a significant association between anti-RA33 and the clinical features of CTDs, especially SLE, indicating a potential clinical significance of anti-RA33 in the management of SLE. [ABSTRACT FROM AUTHOR]

Background: Fabry disease (FD) is an X-linked condition caused by variants in the GLA gene. Since females have two X chromosomes, they were historically thought to be carriers. Although increased knowledge has shown that females often develop the disease, data from Spain and other countries reported that females were undertreated. The aim of this study was to provide a wider and more recent description of the disease characteristics and associated management of females with a GLA variant in a Spanish cohort. Results: Ninety-seven females from 12 hospitals were included in this retrospective study. Mean age was 50.1 ± 17.2 years. Median follow-up time from GLA variant identification was 36.1 months, and most (70.1%) were identified through family screening. Variants associated with classic/non-classic phenotypes were similarly distributed (40.2%/53.6%). Missense variants were the most prevalent (n = 84, 86.6%). In the overall group, 70.4% had major organ involvement (i.e., cardiac, renal, cerebrovascular, peripheral nervous system or gastrointestinal), and 47.3% also had typical Fabry signs (angiokeratoma, cornea verticillata or increased plasma lyso-Gb3). Cardiac involvement was the most prevalent (49.5%) and the main reason for treatment initiation. A total of 33 (34%) patients received disease-specific therapy, 55% of whom were diagnosed by family screening. Females carrying variants associated with a classic phenotype had higher frequencies of clinical manifestations (92.3%) and were predominant in the treated subgroup (69.7%). Despite this, there were 34 untreated females (56.7% of total untreated), with both phenotypes represented, who had major organ involvement, with 27 of cardiac, renal or cerebrovascular nature. Age or comorbidities in this subgroup were comparable to the treated subgroup (P = 0.8 and P = 0.8, respectively). Conclusions: Efforts have been made in recent years to diagnose and treat timely Fabry females in Spain. A high percentage of females with pathogenic variants, regardless of their associated phenotype, will likely develop disease. A proportion of females with severe disease in this cohort received specific treatment. Still a significant number of females, even with same profile as the treated ones, who may be eligible for treatment according to European recommendations, remained untreated. Reasons for this merit further investigation. [ABSTRACT FROM AUTHOR]

Sarcoidosis may present with many rheumatological symptoms as well as mimic and/or may occur concomitantly with many other rheumatic diseases. We examined the demographic, clinical and laboratory characteristics of patients diagnosed with sarcoidosis in the rheumatology department. This study planned as retrospective cross-sectional study. Medical records of patients who applied to our rheumatology outpatient clinic due to complain of musculoskeletal problems and then diagnosed sarcoidosis were retrospectively investigated. Joint findings, extrapulmonary involvements, and coexisting rheumatic disease were evaluated. Fifty-six patients (41.21 ± 7.83 years, 75% female) were included. The duration of the disease was 49.61 ± 29.11 months, and the follow-up period was 26.66 ± 13.26 months. All patients had pulmonary system involvement. Arthralgia was present in 91.10% of 56 patients and arthritis in 89.29% of patients. Examining the subtypes of the arthritis findings, mono-arthritis was found in 31/50 (62%) patients, oligo-arthritis in 15/50 (30%) patients, and polyarthritis in 4/50 (8%) patients. A total of 11 (19.60%) patients were diagnosed with uveitis. Excision of the mediastinal LAP was performed in a total of 37 patients (66.1%) and became the most commonly employed method. Considering the treatment distribution of the patients under followed-up, it is seen that non-steroidal anti-inflammatory treatments were used in 15 (26.8%) patients, corticosteroids in a total of 40 (71.4%) patients, methotrexate in a total of 15 patients (26.8%), azathioprine in six (10.7%) patients, hydroxychloroquine in 14 (25%) patients, and infliximab in one (1.8%) patient. As sarcoidosis is a mimicking disease, a good differential diagnosis should be made to avoid misdiagnosis and in order not to be late in diagnosis and treatment. Physicians, especially rheumatologists, should remember sarcoidosis more frequently as the disease may overlap with other rheumatological diseases and may occur with many rheumatological manifestations. [ABSTRACT FROM AUTHOR]

Objectives Nailfold videocapillaroscopy (NVC) plays a well-established role in differentiating primary from secondary RP due to SSc. However, the association of NVC with novel severe organ involvement/progression in SSc has never been evaluated in a multicentre, multinational study, which we now perform for the first time. Methods Follow-up data from 334 SSc patients [265 women; 18 limited SSc (lSSc)/203 lcSSc/113 dcSSc] registered between November 2008 and January 2016 by seven tertiary centres in the EUSTAR-database, were analysed. Novel severe organ involvement/progression was defined as new/progressive involvement of the peripheral vasculature, lungs, heart, skin, gastrointestinal tract, kidneys, musculoskeletal system, or death, at the 12- or 24-month follow-up. NVC images at enrolment were quantitatively and qualitatively evaluated according to the standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases. Uni- and multivariable logistic regression modelling (ULR, MLR) was performed. Results Of the 334 included SSc patients, 257 (76.9%) developed novel overall severe organ involvement/progression. Following MLR, normal capillary density was associated with less-frequent novel overall severe organ involvement/progression [odds ratio (OR) = 0.77, P  < 0.001] and novel peripheral vascular involvement (OR = 0.79, P   =  0.043); microhaemorrhages were associated with less novel pulmonary hypertension (OR = 0.47, P   =  0.029); and a 'severe' (active/late) NVC pattern was associated with novel overall severe organ involvement/progression (OR = 2.14, P   =  0.002) and skin progression (OR = 1.70, P   =  0.049). Conclusions Our results suggest that NVC may be a promising biomarker in SSc, certainly warranting further investigation. Despite the participation of tertiary centres, which follow their patients in a standardized way, we were underpowered to detect associations with infrequent severe organ involvement/progression. [ABSTRACT FROM AUTHOR]

We performed a retrospective cohort study in AL amyloidosis to investigate the impact of light chain (LC) isotype on clinical features in 112 consecutive patients. Patients with kappa LC isotype had a significantly higher difference in free light chain (dFLC) (median, 61.5 vs. 21.6 mg/dL, p =.02) and involved/uninvolved FLC ratio (median, 63.5 vs. 10.6, p <.01) compared to lambda. Patients with lambda LC had a higher kidney involvement (64% vs. 38%, p =.02) but similar cardiac involvement rate (75% vs 72%; p =.81) as kappa. The hematologic ≥ VGPR rate after first-line therapy was similar (kappa [61%] vs lambda [68%]; p =.46). At a median follow-up of 43 months for surviving patients, the hazard ratio (kappa/lambda) for event-free survival (EFS) and overall survival (OS) was 0.76 (95% CI, 0.43–1.38; p =.37) and 0.49 (95% CI, 0.19–1.28; p =.14) respectively. Achievement of iFLC < 2 mg/dL and dFLC < 1 mg/dL was predictive of superior OS irrespective of LC isotype. [ABSTRACT FROM AUTHOR]

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Objective: To investigate the effect of cyclophosphamide (CYC) on organ involvement and SLE patients' overall and cause-specific mortality. Methods: Information about CYC prescription was taken from the Jiangsu Lupus database, which was set up to collect medical records from SLE patients since their first admission during 1999–2009 in Jiangsu province, China. Follow-up studies were carried out in 2010 and 2015 to check the survival status of the patients. Cox regression models were used to estimate the hazard ratio (HR) and 95% CI. Kaplan–Meier model was used to assess the effect of CYC on mortality between organ involvement and non-involvement. Results: There were 221 deaths observed out of 2446 SLE patients. CYC users decreased overall mortality of SLE (8.4%) with adjusted HR (95% CI) of 0.74 (0.56–0.97), as compared to non-users. A decrease in overall mortality of SLE was found in the low dosage (< 600 mg) of CYC users, with adjusted HR (95% CI) of 0.54 (0.36–0.81). The protection of CYC on mortality of SLE was further observed in subgroups, such as female; SLEDAI score ≥ 15 group; and those with neuropsychiatric, renal, and hematological involvements, and low serum C3. In addition, CYC could eliminate the differences in mortality between organ involvement and non-involvement, including renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvement, but not for mucocutaneous and musculoskeletal involvement. Conclusion: Low dosage use of CYC decreased the risk of overall mortality of SLE. CYC might improve the survival of SLE patients with renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological involvements. Key Points • Cyclophosphamide decreases overall mortality of SLE patients. • Decreased mortality is mainly observed from low dosage use of cyclophosphamide. • Cyclophosphamide improves the survival of SLE patients when major systems such as renal, neuropsychiatric, cardiopulmonary, gastrointestinal, and hematological are involved. [ABSTRACT FROM AUTHOR]

Precise reasons for severe manifestation of SARS-CoV-2 remain unanswered, and efforts have been focused on respiratory system management. Demonstration of unequivocal presence of SARS-CoV-2 in vital body organs by cadaver autopsy was the only way to prove multi-organ involvement. Hence, the primary objective of the study was to determine presence of the SARS-CoV-2 in various organs of patients succumbing to SARS-CoV-2 infection. A total of 246 samples from different organs of 21 patients who died due to severe COVID-19 illness were investigated by qRT-PCR, and SARS-CoV-2 was detected in 181 (73.57%) samples and highest positivity of SARS-CoV-2 being (expectedly) found in nasopharynx (90.4%) followed by bilateral lungs (87.30%), peritoneal fluid (80%), pancreas (72.72%), bilateral kidneys (68.42%), liver (65%) and even in brain (47.2%). The deceased patients were categorized to three subgroups based upon the extent of organs in which SARS-CoV-2 was detected by qRT-PCR (high intensity ≥80%, intermediate intensity = 65–80% and low intensity ≤65% organs involvement). It was conclusively established that SARS-CoV-2 has the property of invasion beyond lungs and even crosses the blood–brain barrier, resulting in multi-system disease; this is probably the reason behind cytokine storm, though it is not clear whether organ damage is due to direct injury caused by the virus or result of inflammatory assault. Significant inverse correlation was found between the Ct value of lung samples and number of organs involved, implying that higher viral load in lungs is directly proportionate to involvement of extrapulmonary organs and patients with higher viral load in respiratory secretions should be monitored more closely for any warning signs and the treatment strategies should also address involvement of other organs for better outcome, because lungs, though the primary site of infection, are not the only organ system responsible for pathogenesis of systemic illness. [ABSTRACT FROM AUTHOR]

Interleukin 10 (IL-10) plays a role in inflammation and cell-type responses. The anti-SS-A/Ro antibody contributes to leucopenia, and cutaneous and neonatal lupus. Objectives: To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. Patients and methods: We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Results: Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. Conclusions: In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti–SS-A/Ro antibody positivity.

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Introduction. The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Material and method. We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096 . We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 173 patients with SSc were available for the baseline analyses. In the longitudinal analysis after a mean follow-up of 3.5(±0.65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p = 0.004), digital contractures (OR:8.2 (3.1 to 21.9); p < 0.001), arrhythmias (OR: 3.37 (1.36 to 8.34); p = 0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p = 0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7.59); p = 0.016), severe vascular involvement (OR:2.86, (1.22 to 6.73); p = 0.013) and low ventricular ejection fraction (OR: 2.84, (1.2 to 6.73); p = 0.014). Males had significantly reduced survival time after diagnosis (p = 0.004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process.

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The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab's safety and efficacy profile in SSc patients. A systematic online query was performed in PubMed, Scopus, Web of Science, and Embase. The studies on the application of rituximab for patients with SSc were reviewed comprehensively for over two years. In terms of efficacy profile, mRSS, MS, LVEF, sPAP, FVC, DLCO, TLC, FEV, DAS, severity activity, HAQ-DI and SF36 were assessed for organ involvement and quality of life. The level of biological and immunological markers was also evaluated in SSc patients treated with RTX. In total, 24 studies met the criteria. Although they did not have a high quality, they were free from heterogeneity and publication bias. The pooled results revealed a long-term improvement in mRSS and MS. HAQ-DI was improved to 0.78 after 12 months, and DAS was significantly reduced to 0.33, 0.23, and 0.24 following 6, 12, and 24 months of treatment, respectively (p = 0.00 for both parameters). The rest of the parameters remained stable over time in patients with SSc. The pooled analysis of these patients demonstrated that the induction of death, cancer, infection, and infusion were 9, 5, 18 and 10%, respectively. Based on the pooled results of this meta-analysis, rituximab improves skin score and disease indices and stabilizes organ involvement in SSc patients. Rituximab seems to possess reasonable safety, similar to previous data from other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Due to the heterogeneity of sarcoidosis, there is a need to define clinical phenotypes to allow for tailoring of clinical care and identification of more homogenous populations to facilitate research., Methods: We utilized data from a prospectively collected registry of sarcoidosis patients seen at a single quaternary referral center between January 2019 and February 2021. We used multiple correspondence analysis (MCA) and k-means clustering to investigate if the clusters previously identified in the GenPhenReSa study were reproducible in a US population. We also investigated if these clusters were stable when the population was stratified by race., Results: We replicated 3 of the 5 clusters seen in the GenPhenReSa study in our cohort. We likewise identified similar clusters between White and Black patients with sarcoidosis. Differences in organ manifestations associations between White and Black patients were seen primarily in relation to cardiac, neurologic, and ocular involvement., Conclusions: The organ clusters of liver-spleen, isolated pulmonary, and musculoskeletal-skin were reproducible in a US cohort, and in both Black and White patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LJH, AT, SH, XW have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.JCS:Lecture honoraria - Kinevant, Boehringer IngelheimRB:Research Grants - Celgene, Actelion, aTyr, Genentech, Gilead, Bellerophon, Bayer, Mallinckrodt, Foundation for Sarcoidosis Research.Scientific Advisor - Astra Zeneca, Actelion, aTyr, Kinevant, Xentria, Mallinckrodt, Boehringer Ingelheim, Foresee Pharmaceuticals, Ann Theodore Foundation.Speaker's Bureau - Mallinckrodt, United Therapeutics, Boehringer IngelheimDAC:Steering Committee - Boehringer-IngelheimClinical Trials – Atyr, AI Therapeutics, MallinckrodtConsulting – Foresee Pharmaceuticals, Molecure, KinevantCommittee Honoraria – Pliant, FibroGen., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Clinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population., Aim: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands., Methods: Two large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument., Results: Between 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis., Conclusions: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients., Competing Interests: Declaration of competing interest There is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives In SSc patients, disease specific determinants that influence health-related quality of life (HRQoL) over time have not been described. We aim to, in patients with SSc, (i) evaluate if and how HRQoL changes over time, and (ii) assess how different SSc domains and functional impairments contribute to changes in HRQoL over time. Methods All SSc patients from the Leiden SSc cohort were included; patients with disease duration <24 months were classified as incident cases. HRQoL was assessed prospectively on an annual basis using the EQ-5D and the SF36. To assess baseline associations between clinical characteristics and HRQoL, linear regressions were performed. To identify possible associations between SSc characteristics and HRQoL change over time, linear mixed models were performed in both incident and prevalent cases. Results In total, 492 SSc patients were included (n  = 202 incident cases), with a median follow-up duration of 3.4 years. At baseline, presence of organ involvement was independently associated with a worse SF36 physical component score and lower EQ-5D score. Over time, gastrointestinal symptoms, Raynaud and digital ulcers were independently associated with deterioration of HRQoL in both incident and prevalent cases. In prevalent cases, pulmonary arterial hypertension (PAH) was associated with a decrease in HRQoL over time. Worse functioning as measured by six-min walking distance, mouth-opening, finger-to-palm distance and grip-strength contributed significantly to deterioration of HRQoL over time. Conclusion In SSc, key clinical burdens that contribute to worsening of HRQoL over time include digital ulcers, Raynaud and gastrointestinal involvement. In addition, PAH is a significant burden in prevalent disease. [ABSTRACT FROM AUTHOR]

Precise reasons for severe manifestation of SARS-CoV-2 remain unanswered, and efforts have been focused on respiratory system management. Demonstration of unequivocal presence of SARS-CoV-2 in vital body organs by cadaver autopsy was the only way to prove multi-organ involvement. Hence, the primary objective of the study was to determine presence of the SARS-CoV-2 in various organs of patients succumbing to SARS-CoV-2 infection. A total of 246 samples from different organs of 21 patients who died due to severe COVID-19 illness were investigated by qRT-PCR, and SARS-CoV-2 was detected in 181 (73.57%) samples and highest positivity of SARS-CoV-2 being (expectedly) found in nasopharynx (90.4%) followed by bilateral lungs (87.30%), peritoneal fluid (80%), pancreas (72.72%), bilateral kidneys (68.42%), liver (65%) and even in brain (47.2%). The deceased patients were categorized to three subgroups based upon the extent of organs in which SARS-CoV-2 was detected by qRT-PCR (high intensity ≥80%, intermediate intensity = 65–80% and low intensity ≤65% organs involvement). It was conclusively established that SARS-CoV-2 has the property of invasion beyond lungs and even crosses the blood–brain barrier, resulting in multi-system disease; this is probably the reason behind cytokine storm, though it is not clear whether organ damage is due to direct injury caused by the virus or result of inflammatory assault. Significant inverse correlation was found between the Ct value of lung samples and number of organs involved, implying that higher viral load in lungs is directly proportionate to involvement of extrapulmonary organs and patients with higher viral load in respiratory secretions should be monitored more closely for any warning signs and the treatment strategies should also address involvement of other organs for better outcome, because lungs, though the primary site of infection, are not the only organ system responsible for pathogenesis of systemic illness.

Introduction: Systemic sclerosis is a chronic multisystem disorder of unknown etiology characterized clinically by thickening of the skin caused by the accumulation of collagen and by structural and functional abnormalities of visceral organs including the gastrointestinal tract, lungs, heart, and kidneys. Systemic sclerosis is often of tragic consequence to patients. Survival is determined by the severity of the visceral disease, especially involving the lungs, heart, and/or kidneys. Aim of the study: To study the clinical spectrum of patients presenting with Systemic Sclerosis (SSc) and to evaluate the internal organ involvement. Materials and methods: Patients who attended the General Medicine Department of Government Headquarters Hospital, Kallakurichi, Tamil Nadu from January 2019 to September 2019 were taken up for the study. Systemic sclerosis was diagnosed in 25 patients as per the American College of Rheumatology. Results: The initial presentation was skin manifestation (52%) Arthralgia (40%), Raynaud's (8%) Visceral symptom (4%), Cumulative manifestations included skin (Cutaneous) 100%, Diffuse skin Involvement was seen in (4%), Arthralgia (80%). No one presented with fully developed CREST syndrome. Calcinosis - Nil, Reynaud's was 28%. Joint involvement in the form of arthralgia was seen in 80%. Gastro-Intestinal system was involved in 72%. The respiratory system was involved in 16%. The cardiovascular system was involved in 16%. The renal system was not involved even in one case. Conclusion: Sclerodactyly and pigmentary changes are more common. Raynaud's phenomenon is very much less probably due to climatic causes. A fully developed CREST was not present in this study. Resorptions of terminal phalanges were less common. Gastrointestinal involvement is more than in other studies. Respiratory involvement was low compared to other studies. Cardiac involvement is less like other studies. Renal involvement is NIL in this study. [ABSTRACT FROM AUTHOR]

Introduction. The low overall prevalence of systemic sclerosis (SSc) and the low proportion of male patients have resulted in a scarcity of studies assessing sex differences in SSc patients, and contradictory results have often been observed. Material and method. We performed a retrospective observational study using data extract from the EULAR scleroderma trials and research (EUSTAR) cohort 096 . We looked at sex influence on disease characteristics at baseline and then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. Results. 173 patients with SSc were available for the baseline analyses. In the longitudinal analysis after a mean follow-up of 3.5(±0.65) years, male sex was associated with a higher risk of scleroderma renal crisis (OR:9.45 (1.49 to 59.69); p = 0.004), digital contractures (OR:8.2 (3.1 to 21.9); p < 0.001), arrhythmias (OR: 3.37 (1.36 to 8.34); p = 0.006), pulmonary fibrosis (OR: 3.56, (1.51 to 8.41); p = 0.003), pulmonary hypertension (OR: 3.01 (1.19 to 7.59); p = 0.016), severe vascular involvement (OR:2.86, (1.22 to 6.73); p = 0.013) and low ventricular ejection fraction (OR: 2.84, (1.2 to 6.73); p = 0.014). Males had significantly reduced survival time after diagnosis (p = 0.004). The most frequent causes of death were scleroderma renal crisis in males and pulmonary hypertension in females. Conclusions. Although more common in women, SSc appears as strikingly more severe in men. Our results demonstrate a higher risk of severe organ involvement and poor prognosis in men. These results raise the point of including sex in the management and the decision-making process. [ABSTRACT FROM AUTHOR]

Abstract Chronic urticaria is a disease characterized by the appearance of weals, angioedema or both longer than 6 weeks. Degranulation of cutaneous or submucosal mast cells leads to release of mediators including histamine resulting in redness, swelling and itch. Because mast cells are widely distributed throughout the body, the question is why they are not activated systemically or does systemic activation occur without overt end organ dysfunction? We have conducted an exploratory literature search for reports that have evidence of organ-specific dysfunction in chronic urticaria that might justify prospective observational studies. This search revealed some evidence of systemic effects of chronic urticaria in cardiac, respiratory, gastrointestinal, central nervous and musculo-skeletal systems. The relevance of these findings needs to be further determined. However, they justify prospective studies in larger numbers of patients and at different stages of disease activity.

Objectives: to estimate the effect of complement level changes on clinical manifestations, visceral damage and mortality in our patients with SLE. Patients and method(s): A cross sectional study including 50 patients attending to South Valley University Hospitals have been included in the study for assessment of complement levels in patients with SLE and correlating complement levels with renal, neuropsychiatric, cardiac and hematological manifestations of SLE. Result(s): The most common organ system involved was the musculoskeletal system, with arthritis in 76% of the cases. This was followed by cutaneous manifestations (72%), then lupus nephritis (62%), CNS lupus (44%), hematological (30%) and lastly CVS (12%). Non of our cases showed liver impairment. Around two thirds of patients with renal involvement had consumed complement, compared to only 26% among those with no renal involvement; with a significant difference. It also shows that there is no significant difference between hypertension and complement level. Over 72% of patients with CNS involvement had consumed complement, compared to only 32% among those with no CNS involvement; with a significant difference. There is no significant relation between blood disorders, arthritis, mucocutaneous in lupus patients and complement consumption. Conclusion: Our study suggested that complement consumption was strongly associated with lupus nephritis and to a lesser extent; CNS lupus, but not with other organ involvement in SLE patients.

Adult-onset Still’s disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy.

Objective: The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection., Methods: This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months., Results: A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months., Conclusion: In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Zhang, Liu, Liu, Zhao, Zhou, Ruan, Shi and Liu.)

The aim of this study is to evaluate the therapeutic effect of mesenchymal stem cells (MSCs) in a severe case of brain and multiple organ involvement in a patient with COVID-19. Here, a 51-year-old male patient with multi-organ involvement due to COVID-19 infection and developing cardiac arrest is presented. MSCs were transplanted to the patient four times systematically and once intrathecally. As a result, the application of MSCs has been found to have a healing effect on organs in this patient with severe COVID-19 infection. In addition, transplantation of MSCs both systematically and intrathecally is considered to be effective in the treatment of the central nervous system. [ABSTRACT FROM AUTHOR]

Adult-onset Still's disease (AOSD) is an autoinflammatory disease with multisystem involvement. Early identification of patients with severe complications and those refractory to glucocorticoid is crucial to improve therapeutic strategy in AOSD. Exaggerated neutrophil activation and enhanced formation of neutrophil extracellular traps (NETs) in patients with AOSD were found to be closely associated with etiopathogenesis. In this study, we aim to investigate, to our knowledge for the first time, the clinical value of circulating NETs by machine learning to distinguish AOSD patients with organ involvement and refractory to glucocorticoid. Plasma samples were used to measure cell-free DNA, NE-DNA, MPO-DNA, and citH3-DNA complexes from training and validation sets. The training set included 40 AOSD patients and 24 healthy controls (HCs), and the validation set included 26 AOSD patients and 16 HCs. Support vector machines (SVM) were used for modeling and validation of circulating NETs signature for the diagnosis of AOSD and identifying patients refractory to low-dose glucocorticoid treatment. The training set was used to build a model, and the validation set was used to test the predictive capacity of the model. A total of four circulating NETs showed similar trends in different individuals and could distinguish patients with AOSD from HCs by SVM (AUC value: 0.88). Circulating NETs in plasma were closely correlated with systemic score, laboratory tests, and cytokines. Moreover, circulating NETs had the potential to distinguish patients with liver and cardiopulmonary system involvement. Furthermore, the AUC value of combined NETs to identify patients who were refractory to low-dose glucocorticoid was 0.917. In conclusion, circulating NETs signature provide added clinical value in monitoring AOSD patients. It may provide evidence to predict who is prone to be refractory to low-dose glucocorticoid and help to make efficient therapeutic strategy. [ABSTRACT FROM AUTHOR]

Introduction: Systemic sclerosis (SSc) is an autoimmune connective tissue disease with distinguished fibrosis of the skin and internal organs. Vascular damage, immune dysregulation and fibroblasts activation contribute to SSc pathogenesis. Peroxisome proliferator-activated receptor γ (PPAR-γ) can be a link between cell metabolism and fibrosis in SSc due to its anti-fibrotic and immunomodulatory properties. Aim: To measure the serum level of PPAR-γ in SSc patients and correlate it with the SSc subtype, hs-CRP, disease duration, vascular and internal organ involvement. Material and methods: Twenty-two SSc patients (15 limited SSc, 7 diffuse SSc) matched with healthy controls were analysed. Clinical and laboratory data were collected including specific antibodies, interstitial lung disease, oesophageal involvement, digital pitting scars, disease duration, Raynaud's phenomenon (RP) and modified Rodnan skin score (mRSS). PPAR-γ levels were analysed by ELISA. Statistical analysis was performed with c2, Student's t-test and Mann-Whitney-U test. Pearson and Spearman correlation analyses were used to establish variables association. The significance threshold was set at p < 0.05. Results: PPAR-γ concentration was elevated in SSc patients in comparison to controls (p = 0.007) with the highest difference for diffuseSSc (p = 0.004) with significantly elevated mRSS. No association between PPAR-γ levels and hs-CRP, internal organ and vascular involvement, disease duration, autoantibodies and RP onset was found. Conclusions: The present study revealed elevated serum PPAR-γ in SSc patients, in particular those with a diffuse form, presenting highest mRSS and lowest BMI. Whether circulating PPAR-γ originates from atrophic adipose tissue, reperfused vessels or ischemic tissues needs assessing. Also the biological meaning or effect of elevated serum PPAR-γ requires further studies. [ABSTRACT FROM AUTHOR]

Objective: Scleroderma (SSc) is a chronic inflammatory autoimmune disease characterized by fibrosis in the skin and internal organs. In SSc, the heart, lung, kidney, gastrointestinal (GIS) system, muscle, and peri‐articular structures are damaged. There is no study of the relationship between SSc type, stage, pathogenesis, organ involvement, and Wnt signaling. In this study, we aimed to show the relationship of the Wnt gene family and antagonists in SSc subtypes and different organ involvement. Methods: Eighty‐five SSc patients and 77 controls were included in this study. The gene expressions and protein levels of the Wnt family and antagonists were analyzed from blood samples. The relationship between these parameters and disease stage, type, and organ involvement were evaluated. Results: Wnt‐1, Wnt‐10b, Wnt‐2, and Wnt‐6 gene expressions are increased and Axin‐2, DKK‐1, and Kremen protein expressions are decreased in SSc. Wnt‐3a and Wnt‐10a gene expressions are increased in generalized SSc compared to limited SSc. Wnt‐1, Wnt‐2 gene expressions are increased significantly in pulmonary arterial hypertension (PAH)(+) SSc compared to PAH(−) SSc. There was a positive correlation between the modified Rodnan skin score and Wnt‐2 in SSc. There was a significant positive correlation between GIS involvement score and Wnt‐1, Wnt‐2, Wnt‐4, Wnt‐8a, Wnt‐9b in SSc. Conclusion: Wnt‐1 and Wnt‐2 were found higher in scleroderma and organ involvement. They may play a role in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]