Reproductive organ involvement in women undergoing radical cystectomy for urothelial bladder cancer: a nationwide multicenter study.

BACKGROUND: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear. METHODS: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves. RESULTS: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck. CONCLUSIONS: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully.

Blood soluble CD89-IgA complex may be a potential biomarker for predicting multi-organ involvement, especially renal involvement in children with immunoglobulin A vasculitis.

BACKGROUND: Immunoglobulin A vasculitis (IgAV) is a kind of systemic vasculitis mediated by IgA immune complexes (IgA-ICs). Soluble CD89-IgA complex (sCD89-IgA) as a type of IgA-IC associated with renal involvement in IgAV, the ability of blood sCD89-IgA as a biomarker to predict renal or multi-organ involvement in children with IgAV is not evident, and this study mainly focused on this. METHODS: The clinical characteristics and blood samples of 57 pediatric patients with IgAV were collected. ELISA was used to detect plasma IgA-ICs and sCD89-IgA levels. Serum IgA levels were detected by Nephelometry method. Statistical analysis was conducted to analyze the relationship between sex, age, serum IgA levels, plasma IgA-ICs levels, plasma sCD89-IgA levels and the involvement of multiple organs (except skin) including kidneys in these patients. RESULTS: Compared to patients with simple skin involvement, patients with multi-organ involvement, especially kidneys, had higher levels of plasma IgA-ICs and sCD89-IgA, and the statistical difference was significant. In addition, a high level of plasma sCD89-IgA was a high-risk factor for patients to develop multi-organ or renal involvement in addition to the skin. ROC curve analysis showed that the AUC was 0.861 (Sensitivity: 83 %, Specificity: 88 %, p < 0.0001) when plasma sCD89-IgA predicted multi-organ involvement, and AUC 0.926 (Sensitivity: 94 %, Specificity: 88 %, p < 0.0001) for predicting renal involvement. CONCLUSIONS: The results suggested that plasma sCD89-IgA may be a potential biomarker for predicting multi-organ involvement (in addition to skin), especially renal involvement in IgAV pediatric patients.

Autoantibodies in systemic sclerosis overlap syndrome and their correlation with organ damage and survival.

BACKGROUND: Systemic sclerosis (SSc) often overlaps with other autoimmune diseases. More complex autoantibody profiles may be observed in SSc overlap syndrome (SSc OS). To determine the clinical significance of autoantibodies in SSc OS and classify the patients more accurately for better disease assessments, we analysed the correlation between serological profiles, organ involvements and outcomes. METHODS: A retrospective cohort study was conducted in Peking University People's Hospital. Chi-square tests and analysis of variance were used to analyse univariate comparisons of clinical symptoms, organ involvement and laboratory indicators. Survival was evaluated using Cox proportional hazards model. RESULTS: Among 141 cases, anti-Ro-52 was the most common antibody, followed by anti-centromere antibody and anti-Scl-70 antibody. We analysed the correlation between autoantibodies and vital organ damage in SSc OS patients, and compared the differences across four SSc OS subgroups (SSc SLE, SSc RA, SSc PM/DM and SSc SS) to demonstrate the correlation between autoantibodies and clinical characteristics and organ damage. Cox regression analysis showed that scleroderma renal crisis (SRC) (p = .004) and pulmonary arterial hypertension (PH) (p = .010) were independent risk factors for survival. CONCLUSIONS: Autoantibodies are associated with clinical features, organ involvement and prognosis in SSc OS patients. Anti-Scl-70 antibody is associated with interstitial lung disease (ILD) and SRC, while ACA is a protective factor of ILD. SRC and PH are risk factors associated with death.

A histopathological analysis of extrapulmonary lesions in fatal coronavirus disease (COVID-19).

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents diverse clinical manifestations and multi-organ involvement. This study aimed to evaluate the extra-pulmonary histopathological patterns underpinning COVID-19-induced lesions in cardiac, hepatic, renal, brainstem, and splenic tissues. MATERIALS AND METHODS: The research involved conventional forensic autopsies conducted between April 2020 and April 2021 on individuals with confirmed SARS-CoV-2 infection in Cluj-Napoca, Romania. Tissues were processed and stained for histological examination. Differences in patients with and without diffuse alveolar damage (DAD) were evaluated. RESULTS: In our study of 79 COVID-19 autopsies conducted on unvaccinated patients besides lung involvement, the patients had histological changes in at least two out of five (brain, heart, liver, kidney, and spleen) organs. Notable findings include hepatitis observed in 46.8 % of cases, 21.5 % with lobular hepatitis, and 41.8 % with liver steatosis. Additionally, 69.6 % exhibited acute tubular necrosis, and 55.7 % had varying degrees of splenic lymphocyte depletion. Almost 41 % of cases had pericardial effusion, 36.7 % myocarditis, 24.1 % myocardial infarction, and 12.7 % of cases had encephalitis. Acute tubular necrosis (78.6 %) was the most frequent histopathological finding observed in patients with DAD. Myocarditis was described in 45.9 % of the patients without DAD. DISCUSSION: The autopsy findings in our cohort of COVID-19 victims align with international scientific literature. Distinguishing viral-induced myocarditis, encephalitis, hepatitis, or systemic inflammatory syndrome remains challenging. CONCLUSION: Post-mortem analysis identified lesions associated with SARS-CoV-2 in multiple organs, highlighting the systemic nature of the virus and emphasizing the need for continued research into organ-specific damage and long-term sequelae of COVID-19.

Clinical features of patients with systemic sclerosis positive for anti-SS-A antibody: a cohort study of 156 patients.

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.

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study.

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.

Comparison of organ involvement clusters in Black and White American sarcoidosis patients from a prospectively collected patient registry.

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.

Clinical features and prognosis of systemic lupus erythematosus complicated by active cytomegalovirus infection: a retrospective cohort study.

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.

Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis.

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.

Gynaecological organ involvement in females undergoing radical cystectomy: a multicentre study.

OBJECTIVE: To report the incidence of malignancy in gynaecological organs removed during radical cystectomy (RC). PATIENTS AND METHODS: A retrospective multicentre study of 1600 RCs at three high-volume institutions between January 2009 and March 2022 was performed. Pathological findings in gynaecological organs in female RC specimens were reviewed. Multivariable logistic regression analyses were used to identify predictors of malignant gynaecological organ involvement (GOI) at time of RC. RESULTS: Overall, 302 females with a median (interquartile range) age of 68 (61-75) years underwent RC for clinical (c)Ta-T4 bladder cancer. In all, 56 patients (18.5%) received neoadjuvant chemotherapy. Malignant GOI was seen in 20 patients (6.6%); the most common single sites of GOI were the uterus (five patients) and vaginal wall (four), followed by cervix (one), and ovaries (one). Nine patients had involvement of more than one gynaecological organ. No females had a primary gynaecological malignancy detected incidentally at RC. Patients with GOI were more likely to have cT3/T4 stage (P < 0.001), preoperative hydronephrosis (P = 0.004), lymphovascular invasion (P = 0.002), and squamous cell carcinoma (P = 0.005) than those without GOI. On multivariable analysis, cT4 stage was an independent predictor of malignant GOI (odds ratio 88.3, 95% confidence interval 10.1-1214; P < 0.001). CONCLUSION: To our knowledge, we present the largest multi-institutional study examining malignant GOI in females with bladder cancer undergoing RC. The rate of GOI at the time of RC is low and associated with higher clinical stage. In the absence of clinical or radiological evidence of sexual organ involvement, our results do not support their routine removal at the time of RC.

Infrequent organ involvement in immunoglobulin G4-related prostate disease: A case report.

BACKGROUND: Immunoglobulin G4-related prostate disease (IgG4-RPD) characterized by a high count of IgG4-positive plasma cells has distinctive serological and radiological findings. Here we report a case of a patient who was successfully treated for IgG4-RPD, which manifested as frequent micturition, dysuric, and systemic lymphadenopathy. CASE SUMMARY: The patient was a 33-year-old man who was referred to our hospital because of urinary tract symptoms that had persisted for 4 years. A physical examination revealed systemic lymphadenopathy and blood tests showed hyperglobulinemia with an IgG level of 18.90 g/L and an IgG4 level of 18.40 g/L. Computed tomography (CT) revealed bilateral lacrimal gland, right parotid gland and prostatic enlargement. Based on these findings, IgG4-RD was suspected, and further pathological examination and follow-up results showed expected results. Finally, the patient was diagnosed with IgG4-RPD based on clinical symptoms, pathological examination, therapeutic effects, and follow-up results. He received 50 mg oral prednisolone (the dose was gradually reduced and a low dose was used for long-term maintenance) in combination with cyclophosphamide 1.0 g via an intravenous drip for 6 mo. One year after the treatment was initiated, he was free of urinary or other complaints and his serum IgG4 level normalized. CONCLUSION: In IgG4-RPD with severe urinary tract symptoms, radiological findings should be carefully examined. IgG4-RPD prognosis is good because the disease responds well to glucocorticoids. Furthermore, it is urgent for clinicians and pathologists to improve their understanding of IgG4-RPD.

A landscape on disorders following different COVID-19 vaccination: a systematic review of Iranian case reports.

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.

Rare manifestations of cryoglobulinemic vasculitis: a case report.

Introduction: Cryoglobulinemic vasculitis is a type of small vessel vasculitis diseases that can cause dysfunction in multiple organs. It is characterized by general symptoms, often accompanied by nonspecific cutaneous, articular, neurological, and renal manifestations. Diagnosing cryoglobulinemia through biological testing can be time-consuming and sometimes yields negative results, making diagnosis challenging. There are also other potentially life-threatening complications that can significantly impact prognosis and delay urgent treatment, including digestive manifestations and heart failure. Case presentation: We report the case of a 60-year-old male patient with a medical history of rheumatoid arthritis. He was admitted to the Nephrology Department for investigation of necrotic vascular purpura, acute kidney injury, and pancytopenia. Laboratory tests revealed consumption of the C3 and C4 complement fractions and the presence of mixed-type III cryoglobulinemia. Despite the initiation of the treatment, the patient rapidly developed multiple severe organ failures, including renal, cardiac, respiratory, and finally digestive complications. Acute colic ischemia led to emergency surgery and the patient was transferred to the Intensive Care Unit. Despite surgical intervention and hemodynamic support, the patient experienced multi-visceral organ failure and died two hours after admission. Discussion: Mixed cryoglobulinemia vasculitis may result in rare cases of acute and life-threatening organ damage, such as cardiac or respiratory failure with pulmonary hemorrhage, gastrointestinal ischemia, and neurological disorders. These severe manifestations are associated with a poor prognosis and it is crucial to promptly initiate an aggressive therapeutic strategy.

SACE and IL-2R as serum biomarkers for evaluation of multi-organ involvement and prognosis of 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.

Research progress on mesenchymal stem cells and their exosomes in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease with an unknown etiology. Clinically, it is characterized by localized or diffuse skin thickening and fibrosis. The pathogenesis of SSc includes microvascular injury, autoimmune-mediated inflammation, and fibroblast activation. These processes interact and contribute to the diverse clinicopathology and presentation of SSc. Given the limited effectiveness and substantial side effects of traditional treatments, the treatment strategy for SSc has several disadvantages. Mesenchymal stem cells (MSCs) are expected to serve as effective treatment options owing to their significant immunomodulatory, antifibrotic, and pro-angiogenic effects. Exosomes, secreted by MSCs via paracrine signaling, mirror the effect of MSCs as well as offer the benefit of targeted delivery, minimal immunogenicity, robust reparability, good safety and stability, and easy storage and transport. This enables them to circumvent the limitations of the MSCs. When using exosomes, it is crucial to consider preparation methods, quality standards, and suitable drug delivery systems, among other technical issues. Therefore, this review aims to summarize the latest research progress on MSCs and exosomes in SSc, offering novel ideas for treating SSc.

Clinical features and relapse risks factors of IgG4 related disease: a single-center retrospective study.

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.

Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus.

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.

Serum salusin-ß levels in patients with systemic lupus erythematosus.

OBJECTIVE: Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-ß with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-ß 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-ß 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-ß 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-ß was significantly higher. In addition, in patients with serositis, serum salusin-ß was significantly lower. Multiple linear regression analysis showed that serum salusin-ß levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. CONCLUSIONS: Our findings showed that salusin-ß might have a possible role in the pathogenesis of SLE. Salusin-ß may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-ß levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-ß levels with age and SLEDAI. • Serum salusin-ß levels retained a significant association with nephritis and thrombosis.