Age-standardized incidence, prevalence, and mortality rates of autoimmune diseases in adolescents and young adults (15-39 years): an analysis based on the global burden of disease study 2021.

BACKGROUND: Autoimmune diseases (ADs) present significant health challenges globally, especially among adolescents and young adults (AYAs) due to their unique developmental stages. Comprehensive analyses of their burden are limited. This study leverages the Global Burden of Disease (GBD) 2021 data to assess the global, regional, and national burden and trends of major ADs among AYAs from 1990 to 2021. METHODS: Utilizing data from the Global Burden of Disease (GBD) Study 2021 for individuals aged 15-39 years, we employed a direct method for age standardization to calculate estimates along with 95% uncertainty intervals (UIs) for assessing the age-standardized incidence rates (ASIR), prevalence rates (ASPR), and mortality rates (ASMR) of ADs. The diseases analyzed included rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes mellitus (T1DM), Asthma, and Psoriasis. Trends from 1990 to 2021 were analyzed using Joinpoint regression, providing average annual percentage changes (AAPC) and 95% confidence intervals (CIs). RESULT: In 2021, the global ASIR, ASPR, and ASMR of RA among AYAs (per 100,000 population) were 9.46 (95% UI: 5.92 to 13.54), 104.35 (77.44 to 137.84), and 0.016 (0.013 to 0.019), respectively. For IBD, the corresponding rates were 4.08 (3.07 to 5.37), 29.55 (23.00 to 37.83), and 0.10 (0.07 to 0.12). MS exhibited rates of 1.40 (0.93 to 1.93), 16.05 (12.73 to 19.75), and 0.05 (0.04 to 0.05), respectively. T1DM had rates of 6.63 (3.08 to 11.84), 245.51 (194.21 to 307.56), and 0.54 (0.47 to 0.60). Asthma demonstrated rates of 232.22 (132.11 to 361.24), 2245.51 (1671.05 to 2917.57), and 0.89 (0.77 to 1.08). Psoriasis showed rates of 55.08 (48.53 to 61.93) and 426.16 (394.12 to 460.18) for ASIR and ASPR, respectively. From 1990 to 2021, the global ASIR of RA (AAPC = 0.47, 95% CI: 0.46 to 0.49), IBD (0.22 [0.12 to 0.33]), MS (0.22 [0.19 to 0.26]), T1DM (0.83 [0.80 to 0.86]), and Psoriasis (0.33 [0.31 to 0.34]) showed increasing trends, whereas Asthma (-0.96 [-1.03 to -0.88]) showed a decreasing trend. The global ASPR of RA (0.70 [0.68 to 0.73]), MS (0.35 [0.32 to 0.37]), T1DM (0.68 [0.66 to 0.69]), and Psoriasis (0.29 [0.27 to 0.32]) also showed increasing trends, whereas IBD (-0.20 [-0.27 to -0.13]) and Asthma (-1.25 [-1.31 to -1.19]) showed decreasing trends. Notably, the estimated global ASMR of RA (-2.35 [-2.57 to -2.12]), MS (-0.63 [-0.86 to -0.41]), T1DM (-0.35 [-0.56 to -0.14]), and Asthma (-1.35 [-1.44 to -1.26]) in AYAs declined. Additionally, the burden of disease for ADs in AYAs varies considerably across continents and between 204 countries and territories. CONCLUSION: ADs among AYAs present a substantial public health burden with notable regional disparities in incidence, prevalence, and mortality rates. Understanding these patterns is essential for developing targeted public health interventions and policies to mitigate the impact of ADs in this population.

Does autoimmune disease impair the survival of hepatocellular carcinoma patients undergoing liver resection? A multi-institutional observational study.

BACKGROUND: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies. METHODS: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality. RESULTS: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (-) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence. CONCLUSION: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.

Risk and survival of patients with non-small cell lung cancer and pre-existing autoimmune disorders receiving immune checkpoint blockade therapy: Survival analysis with inverse probability weighting from a nationwide, multi-institutional, retrospective study (NEJ047).

BACKGROUND: The risk and survival of patients with non-small cell lung cancer (NSCLC) with pre-existing autoimmune disorders (AIDs) receiving immune checkpoint blockade (ICB) therapy have not been clearly established. PATIENTS AND METHODS: This multi-institutional, retrospective cohort study was conducted in collaboration with 20 centers in Japan. RESULTS: In total, 229 patients with advanced or recurrent NSCLC and pre-existing AID, with or without ICB treatment from January 2010-February 2020, were included and analyzed. Among 69 patients who received ICB, 2 received two lines of ICBs with a total of 71 ICB treatments; 57 (80.3 %) and 14 (19.7 %) patients received ICB monotherapy and combination therapy, respectively. AID flares were observed in 18 patients (25.4 %, 95 % confidence interval [CI], 15.8-37.1 %) receiving ICB. AID exacerbations were more likely when NSCLC was diagnosed less than 1 year after the AID diagnosis (odds ratio 5.26 [95 % CI, 1.40-21.61]; P = 0.016). Immune-related adverse events were observed in 32 patients (45.1 %, 95 % CI, 33.2-57.3 %); 17 had grade 3 or higher. The safety profile of combination immunotherapy was not significantly different from that of the monotherapy. After inverse probability weighting, the use of ICB prolonged survival (hazard ratio 0.43 [95 % CI, 0.26-0.70]; P = 0.0006). CONCLUSIONS: These findings revealed a novel risk factor for AID flares following ICB treatment, that is the diagnosis of NSCLC within 1 year of AID diagnosis, and showed that ICBs may improve survival in this population. These results support the utilization of ICB in patients with NSCLC and pre-existing AID.

Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients With Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis.

ABSTRACT: Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean corrected QT (QTc) interval and odds ratio of prolonged QTc interval in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc (10.29 ms,  P  = 0.458) among HCQ users compared to non-HCQ users in patients with RA. There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc compared to non-HCQ users (odds ratio 1.57, 95% CI, 1.19, 2.08). The results of this study suggest that clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring for patients on HCQ for the treatment of systemic autoimmune rheumatic diseases.

Hospitalization and mortality in Asian autoimmune bullous dermatosis patients: A 17-year retrospective study.

Limited data exist on the factors associated with hospitalization and mortality in Asian inpatients with autoimmune bullous dermatoses (AIBDs). This study aimed to elucidate the risk factors affecting hospitalization and mortality rates in Asian patients with AIBDs. A retrospective analysis of patients with AIBDs treated at Siriraj Hospital during a 17-year period was performed using the International Classification of Diseases 10th revision codes. The characteristics of inpatients and outpatients were compared, and mortality rates and associated factors were identified. The study included 360 AIBD patients (180 inpatients, 180 outpatients). Inpatients were significantly younger than outpatients. The identified risk factors for hospitalization were malignancy (odds ratio [OR] 2.83, 95% confidence interval [CI] 1.13-8.04; p = 0.034), moderate to severe disease (OR 2.52, 95% CI 1.49-4.34; p < 0.001), systemic corticosteroid use ≥15 mg/day (OR 2.27, 95% CI 1.21-4.41; p = 0.013) and oral cyclophosphamide treatment (OR 9.88, 95% CI 3.82-33.7; p < 0.001). Kaplan-Meier analysis revealed mortality rates of 26%, 36% and 39% for inpatients with pemphigus at 1, 3 and 5 years, respectively. For inpatients with pemphigoid, the corresponding rates were 28%, 38% and 47%. Infections, particularly pneumonia, were the predominant cause of death in both conditions. This study confirmed that both Asian ethnicity and healthcare disparities may be correlated with adverse outcomes in patients with AIBDs. Pemphigus mortality rates were substantially greater in Asian patients than in Caucasian patients. Continuous monitoring of factors contributing to hospitalization and mortality is imperative to improve treatment outcomes.

Systemic inflammatory autoimmune disease before allogeneic hematopoietic stem cell transplantation is a risk factor for death in patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.

Pursuing living donor liver transplantation improves outcomes of patients with autoimmune liver diseases: An intention-to-treat analysis.

Living donor liver transplantation (LDLT) offers the opportunity to decrease waitlist time and mortality for patients with autoimmune liver disease (AILD), autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. We compared the survival of patients with a potential living donor (pLDLT) on the waitlist versus no potential living donor (pDDLT) on an intention-to-treat basis. Our retrospective cohort study investigated adults with AILD listed for a liver transplant in our program between 2000 and 2021. The pLDLT group comprised recipients with a potential living donor. Otherwise, they were included in the pDDLT group. Intention-to-treat survival was assessed from the time of listing. Of the 533 patients included, 244 (43.8%) had a potential living donor. Waitlist dropout was higher for the pDDLT groups among all AILDs (pDDLT 85 [29.4%] vs. pLDLT 9 [3.7%], p < 0.001). The 1-, 3-, and 5-year intention-to-treat survival rates were higher for pLDLT versus pDDLT among all AILDs (95.7% vs. 78.1%, 89.0% vs. 70.1%, and 87.1% vs. 65.5%, p < 0.001). After adjusting for covariates, pLDLT was associated with a 38% reduction in the risk of death among the AILD cohort (HR: 0.62, 95% CI: 0.42-0.93 [ p <0.05]), and 60% among the primary sclerosing cholangitis cohort (HR: 0.40, 95% CI: 0.22-0.74 [ p <0.05]). There were no differences in the 1-, 3-, and 5-year post-transplant survival between LDLT and DDLT (AILD: 95.6% vs. 92.1%, 89.9% vs. 89.4%, and 89.1% vs. 87.1%, p =0.41). This was consistent after adjusting for covariates (HR: 0.97, 95% CI: 0.56-1.68 [ p >0.9]). Our study suggests that having a potential living donor could decrease the risk of death in patients with primary sclerosing cholangitis on the waitlist. Importantly, the post-transplant outcomes in this population are similar between the LDLT and DDLT groups.

Risk of death, thrombotic and hemorrhagic events in anticoagulated patients with atrial fibrillation and systemic autoimmune diseases: an analysis from a global federated dataset.

BACKGROUND: Growing evidence showing that systemic autoimmune diseases (SADs) are associated with a high risk of atrial fibrillation (AF). However, the impact of SAD on the clinical course of AF patients is largely unknown. METHODS: Retrospective cohort study within a federated healthcare network (TriNetX). Using ICD codes, AF patients on anticoagulant therapy were categorized according to the presence of SAD (M32: Systemic Lupus Erythematosus (SLE); M33: Dermato-polymyositis (DMP); M34: Systemic Sclerosis (SSc); M35: Sjogren syndrome). The primary outcomes were the 5-year risks of (1) all-cause death, (2) thrombotic events (ischemic stroke, acute myocardial infarction, deep vein thrombosis, and pulmonary embolism), and (3) bleeding (intracranial (ICH) and gastrointestinal (GI)). Secondary outcomes were each component of the primary outcomes. Cox regression analysis after propensity score matching (PSM) was used to estimate hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: We identified 16,098 AF patients with SAD (68.2 ± 13.4 years; 71.0% female) and 828,772 AF controls (70.7 ± 12.9 years, 41.1% females). After PSM, AF patients with SAD were associated with a higher risk of all-cause death (HR 1.13, 95%CI 1.09-1.71), thrombotic events (HR 1.37, 95%CI 1.32-1.43), and hemorrhagic events (HR 1.41, 95%CI 1.33-1.50) compared to AF controls without SAD. The highest risk of all-cause death and GI bleeding was associated with SSc, while the highest risk of thrombotic events and ICH was associated with SLE. CONCLUSION: AF patients with SAD are associated with a high risk of all-cause death, thrombotic, and hemorrhagic events. These patients merit careful follow-up and integrated care management to improve their prognosis.

In-hospital outcomes and trends of patients with autoimmune diseases undergoing percutaneous coronary intervention: A nationwide analysis.

BACKGROUND: The risk of coronary artery disease is exaggerated in patients with autoimmune diseases (AID). A higher risk of complications has been reported during and after percutaneous coronary intervention (PCI) in these patients. We aimed to analyze the in-hospital outcomes and trends of patients with AID, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD) undergoing PCI. METHOD: We identified all PCI procedures using the National In-patient Sample database from 2016 to 2020. Stratified them into cohorts with RA, SLE and IBD and compared them to cohorts without AID. The Chi-square test and multivariate logistic regression were used for analysis. A p-value <0.005 was considered statistically significant. RESULT: We identified 2,367,475 patients who underwent PCI. Of these, 1.6 %, 0.5 %, and 0.4 % had RA, IBD and SLE respectively. The odds of mortality were lower among patients with IBD (aOR: 0.56; CI 0.38-0.81, p = 0.002) but patients with RA had higher odds of having composite major complications [(MC) including cerebrovascular accident (CVA), cardiac arrest, acute heart failure (AHF), ventricular arrhythmia (VA), major bleeding, and acute kidney injury (AKI)] (aOR: 0.90; CI 0.83-0.98, p = 0.013). Our SLE cohort had higher rates of CVA (p = 0.017) and AKI (p = 0.002). Our cohort with IBD had lower rates of cardiac arrest but had longer hospital length of stay (4.9 days vs 3.9 days) and they incurred higher hospital charges compared to cohort without IBD. CONCLUSION: This study depicts the immediate adverse outcomes observed in patients with AID undergoing PCI. In contrast to those without AID, our cohorts with RA exhibited worse outcomes, as indicated by the higher odds of major complications. IBD is associated with lower risks of in-hospital adverse outcomes but with higher resource utilization.

Short- and Long-Term Mortality of Hospitalized Patients With Autoimmune Rheumatic Diseases and Serious Infections: A National Cohort Study.

OBJECTIVE: Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. METHODS: This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. RESULTS: Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). CONCLUSION: Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD.

Low mortality rate in a large cohort of myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

The mortality rates of individuals with myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are currently unknown. This study aimed to assess the mortality rate in a large cohort of patients with MOGAD. Since none of the patients in our cohort died, we estimated the upper limit of a 95% confidence interval of the crude mortality rate in the cohort to be 2.1%. These data suggest that mortality in MOGAD is lower than that reported in other neuroinflammatory diseases and comparable to the age-adjusted mortality rates of the general population in the United States. Additional studies are warranted to confirm this observation.

Cancer and Autoimmune Diseases: A Tale of Two Immunological Opposites?

The present article compares, side-by-side, cancer and autoimmune diseases in terms of innate and adaptive immune cells involvement, MHC Class I and Class II expression, TGFß effect, immune modulating drugs effect and the effect of reactive oxygen species. The change in the inflammatory immune reaction during the progress of cancer and the effect of this change on the comorbidity of autoimmune diseases and cancer are discussed. The similar inflammatory properties of autoimmune diseases and early cancer, and the contrasting inflammatory properties of autoimmune diseases and advanced cancer elucidate the increased incidence of many types of cancer in patients with pre-existing autoimmune diseases and the decreased cancer-specific mortality of these patients. Stage-dependent effects of reactive oxygen-species on tumor proliferation are an additional probable cause for these epidemiological observations. The relationship: {standardized incidence ratio (SIR)} > {cancer-specific hazard ratio (HR)} for cancer patients with a history of autoimmune diseases is substantiated and rationalized.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects.

Background: Antineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV. Objective: We investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval. Methods: In this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI). Results: The positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10-2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77-2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20-2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24-3.96) after adjusting for confounders. Conclusions: Serum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.

Reduced Mortality Associated With the Use of Metformin Among Patients With Autoimmune Diseases.

Objective: Metformin has been linked to anti-proliferative and anti-inflammatory mechanisms. In this study, we aimed to examine the long-term impact of metformin on mortality and organ damage in patients with autoimmune diseases and type 2 diabetes mellitus (T2DM). Methods: We conducted a cohort study using the National Health Insurance Research Database in Taiwan between 1997 and 2013. Based on metformin and other anti-diabetic agent prescriptions, we categorized all patients with autoimmune diseases into either the metformin group (metformin administration for at least 28 days) or the non-metformin group. The primary outcomes were all-cause mortality and annual admission rate, while the secondary outcome was target organ damage. We followed patients from the index date to the date on which the event of interest occurred, death, or the end of this study. Results: Our cohort study included 3,359 subjects for analysis. During a mean follow up of 5.2 ± 3.8 years, the event rate of all-cause mortality was 228 (33.6%) in the metformin group and 125 (36.9%) in the non-metformin group. The risk of both all-cause mortality and annual number of admissions for autoimmune diseases was significantly lower in the metformin group than in the non-metformin group [hazard ratio (HR) 0.77; 95% CI 0.62-0.96 and risk ratio (RR) 0.81; 95% CI 0.73-0.90, respectively]. Conclusion: Metformin may add benefits beyond T2DM control with regard to reducing all-cause mortality and admission rate, as well as minimizing end-organ injury in lungs and kidneys among patients with autoimmune diseases.

Using Multiple Cause-of-Death Analysis to Estimate Systemic Autoimmune Disease Mortality Burden in Low- and Middle-Income Countries.

Autoimmune diseases are not always recognized as urgent health issues, despite a worldwide prevalence of 4%-5%. Most estimates come from high-income countries, as low- and middle-income countries face more issues of under-reporting. Despite this and the lack of recognition under current reporting practices, the role these diseases play in mortality must be acknowledged. In particular, considering multiple causes of death as opposed to a single cause of death results in a 1.5-4.2-fold increase in deaths classified as relating to autoimmune diseases, evidence of their share in overall mortality burden, a factor important for patient care and healthcare policy decision making. However, formulating such policies and programs for timely, appropriate diagnoses and care is stymied in low- and middle-income countries by the shortage of methodologically sound studies on mortality from systemic autoimmune diseases. This limitation exacerbates inequalities and health gaps among patients in different countries and localities. Multiple cause-of-death methodology has been validated for research on other diseases and demonstrates the mortality burden of these illnesses in countries where traditional methodological approaches, primarily based on prospective cohort studies, are not feasible. Studying mortality from systemic autoimmune diseases by analyzing multiple causes of death with data from national mortality registries is a low-cost alternative to traditional mortality analysis. The objective of this paper is to demonstrate and defend the usefulness of this approach to estimate mortality burden.

Outcome of COVID-19 in hospitalized patients with chronic inflammatory diseases. A population based national register study in Denmark.

OBJECTIVE: COVID-19 has substantial morbidity and mortality. We studied whether hospitalized patients with COVID-19 and chronic inflammatory diseases experienced worse outcomes compared to patients hospitalized with COVID-19 without chronic inflammatory diseases. METHODS: Danish nationwide registers were used to establish a cohort of hospitalized patients with COVID-19 and inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), spondyloarthropathy (SpA), or psoriatic arthritis (PsA) (exposed), and a control cohort without these diseases (unexposed) between March 1, 2020, and October 31, 2020. We compared median length of hospital stay, used median regression models to estimate crude and adjusted differences. When estimating crude and adjusted odds ratio (OR) for continuous positive airway pressure (CPAP) and mechanical ventilation, in-hospital death, 14-day and 30-day mortality, we used logistic regression models. RESULTS: We identified 132 patients with COVID-19 and IBD, RA, SpA, or PsA, and 2811 unexposed admitted to hospital with COVID-19. There were no differences between exposed and unexposed regarding length of hospital stay (6.8 days vs. 5.5 days), need for mechanical ventilation (7.6% vs. 9.4%), or CPAP (11.4% vs. 8.8%). Adjusted OR for in-hospital death was 0.71 (95% CI 0.42-1.22), death after 14-days 0.70 (95% CI 0.42-1.16), and death after 30-days 0.68 (95% CI 0.41-1.13). CONCLUSION: Hospitalized patients with COVID-19 and chronic inflammatory diseases did not have statistically significant increased length of hospital stay, had same need for mechanical ventilation, and CPAP. Mortality was similar in hospitalized patients with COVID-19 and chronic inflammatory diseases, compared to patients hospitalized with COVID-19 and no chronic inflammatory diseases.

COVID-19 in patients with autoimmune diseases: characteristics and outcomes in a multinational network of cohorts across three countries.

OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid coronavirus disease 2019 (COVID-19), but information on their prognosis is lacking. We characterized 30-day outcomes and mortality after hospitalization with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. METHODS: A multinational network cohort study was conducted using electronic health records data from Columbia University Irving Medical Center [USA, Optum (USA), Department of Veterans Affairs (USA), Information System for Research in Primary Care-Hospitalization Linked Data (Spain) and claims data from IQVIA Open Claims (USA) and Health Insurance and Review Assessment (South Korea). All patients with prevalent autoimmune diseases, diagnosed and/or hospitalized between January and June 2020 with COVID-19, and similar patients hospitalized with influenza in 2017-18 were included. Outcomes were death and complications within 30 days of hospitalization. RESULTS: We studied 133 589 patients diagnosed and 48 418 hospitalized with COVID-19 with prevalent autoimmune diseases. Most patients were female, aged ≥50 years with previous comorbidities. The prevalence of hypertension (45.5-93.2%), chronic kidney disease (14.0-52.7%) and heart disease (29.0-83.8%) was higher in hospitalized vs diagnosed patients with COVID-19. Compared with 70 660 hospitalized with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2-4.3% vs 6.32-24.6%). CONCLUSION: Compared with influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality.

Validation of the Clinical Assessment Scale in Autoimmune Encephalitis in Chinese Patients.

Background and Objectives: The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) is a scale for assessing severity in autoimmune encephalitis. We aimed to validate the CASE score in a Chinese population and evaluate its clinical significance. Methods: Patients diagnosed with autoimmune encephalitis were recruited between June 2014 and May 2019 from two hospitals. CASE and modified Rankin Scale (mRS) scores were obtained. Data regarding clinical features, treatment, and available information were gathered from the hospital information system. Results: Of the 176 patients with autoimmune encephalitis, 11 died and 14 had tumors. Ten patients received second-line treatment. The CASE scores of patients receiving second-line treatment were significantly higher (median CASE: 15) than in those receiving first-line treatment (median CASE: 8) (p<0.001). Twenty-two patients had poor functional status (mRS>2). Areas under the curve of CASE on whether functional status was poor at 1 year were 0.89 (p<0.001). Sixty patients were admitted to the intensive care unit (ICU), and the CASE scores were positively correlated with days in the ICU (r=0.58, p<0.001). There was no statistically significant association between the CASE scores and relapse (p=0.39>0.05). Additionally, the CASE scores were positively associated with the mRS scores (r=0.85 p<0.001). Conclusions: The CASE score is suitable for the comprehensive assessment of Chinese patients with autoimmune encephalitis, which may help clinicians to select the appropriate intervention and estimate the disease severity and prognosis.