Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis.

This meta-analysis assesses antiphospholipid antibodies' (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58-3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26-10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47-4.93, p = 0.001), and anti-ß2 glycoprotein I (aß2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17-2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05-6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Do iron homeostasis biomarkers mediate the associations of liability to type 2 diabetes and glycemic traits in liver steatosis and cirrhosis: a two-step Mendelian randomization study.

BACKGROUND: Previous studies, including Mendelian randomization (MR), have demonstrated type 2 diabetes (T2D) and glycemic traits are associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, few studies have explored the underlying pathway, such as the role of iron homeostasis. METHODS: We used a two-step MR approach to investigate the associations of genetic liability to T2D, glycemic traits, iron biomarkers, and liver diseases. We analyzed summary statistics from various genome-wide association studies of T2D (n = 933,970), glycemic traits (n ≤ 209,605), iron biomarkers (n ≤ 246,139), MASLD (n ≤ 972,707), and related biomarkers (alanine aminotransferase (ALT) and proton density fat fraction (PDFF)). Our primary analysis was based on inverse-variance weighting, followed by several sensitivity analyses. We also conducted mediation analyses and explored the role of liver iron in post hoc analysis. RESULTS: Genetic liability to T2D and elevated fasting insulin (FI) likely increased risk of liver steatosis (ORliability to T2D: 1.14 per doubling in the prevalence, 95% CI: 1.10, 1.19; ORFI: 3.31 per log pmol/l, 95% CI: 1.92, 5.72) and related biomarkers. Liability to T2D also likely increased the risk of developing liver cirrhosis. Genetically elevated ferritin, serum iron, and liver iron were associated with higher risk of liver steatosis (ORferritin: 1.25 per SD, 95% CI 1.07, 1.46; ORliver iron: 1.15 per SD, 95% CI: 1.05, 1.26) and liver cirrhosis (ORserum iron: 1.31, 95% CI: 1.06, 1.63; ORliver iron: 1.34, 95% CI: 1.07, 1.68). Ferritin partially mediated the association between FI and liver steatosis (proportion mediated: 7%, 95% CI: 2-12%). CONCLUSIONS: Our study provides credible evidence on the causal role of T2D and elevated insulin in liver steatosis and cirrhosis risk and indicates ferritin may play a mediating role in this association.

The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

OBJECTIVES: The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. METHODS: Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. RESULTS: Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). CONCLUSION: Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Exploring the impact of acute viral exposure on clinical characteristics and antibody profiles in antiphospholipid syndrome: a study in CAPSTONE.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort.

BACKGROUND: The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. OBJECTIVES: To validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. METHODS: This was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by "expert consensus panel" served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. RESULTS: A total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. CONCLUSION: The 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

Chronic abdominal aortic occlusive disease related to antiphospholipid syndrome: a rare presentation.

OBJECTIVE: Chronic abdominal aortic occlusive disease (CAAOD) is an uncommon manifestation of antiphospholipid syndrome (APS), impacting cardiovascular health and peripheral arterial circulation. We investigated CAAOD in antiphospholipid antibodies (aPL)-positive patients, aimed to offer comprehensive clinical and radiological insights. METHODS: aPL-positive patients with arterial thrombotic events were categorised into CAAOD and non-CAAOD. Extensive data, including clinical features, radiological images and outcomes, were analysed. RESULTS: This case-control study involved 114 patients who experienced arterial events from 2013 to 2021, revealing 12 patients with abdominal aortic stenosis or occlusion. The CAAOD group, predominantly young (36.67±11.83) males (75.00%), exhibited significantly higher rates of critical smoking habits (66.67% vs 25.49%, p=0.006) and hyperhomocysteinaemia (66.67% vs 31.37%, p=0.026). Radiological findings showed long-segment infrarenal aorta stenosis in CAAOD, occasionally involving renal and common iliac arteries. The lesions presented varying degrees of stenosis, including smooth lumen narrow and total vascular occlusion. Treatment modalities typically involved interventions or surgery, complementing anticoagulation therapy. CONCLUSION: The study shed light on the rare occurrence of CAAOD in APS, highlighting the roles of smoking and hyperhomocysteinaemia as notable risk factors. These findings emphasised the significance of early diagnosis and management of CAAOD.

Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study.

There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan-Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57-381) person-years/100,000. The SIR was 5.59 (95%CI:1.81-13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P < 0.001). Furthermore, the value of the IGRA assay decreased after treatment (P < 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.

Comparison of efficacy discrepancy between early-phase clinical trials and phase III trials of PD-1/PD-L1 inhibitors.

BACKGROUND: Phase III clinical trials are pivotal for evaluating therapeutics, yet a concerning failure rate has been documented, particularly impacting oncology where accelerated approvals of immunotherapies are common. These failures are predominantly attributed to a lack of therapeutic efficacy, indicating overestimation of results from phase II studies. Our research aims to systematically assess overestimation in early-phase trials involving programmed cell death-1 (PD-1)/programmed cell death-ligand 1(PD-L1) inhibitors compared with phase III trials and identify contributing factors. METHODS: We matched 51 pairs of early-phase and phase III clinical trials from a pool of over 9,600 PD-1/PD-L1 inhibitor trials. The matching criteria included identical treatment regimens, cancer types, treatment lines, and biomarker enrichment strategies. To assess overestimation, we compared the overall response rates (ORR) between early-phase and phase III trials. We established independent variables related to eligibility criteria, and trial design features of participants to analyze the factors influencing the observed discrepancy in efficacy between the two phases through univariable and multivariable logistic analyses. RESULT: Early-phase trial outcomes systematically overestimated the subsequent phase III results, yielding an odds ratio (OR) comparing ORR in early-phase versus phase III: 1.66 (95% CI: 1.43 to 1.92, p<0.05). This trend of inflated ORR was consistent across trials testing PD-1/PD-L1 monotherapies and combination therapies involving PD-1/PD-L1. Among the examined factors, the exclusion of patients with autoimmune diseases was significantly associated with the disparity in efficacy between early-phase trials and phase III trials (p=0.023). We calculated a Ward statistic of 2.27 to validate the effectiveness of the model. CONCLUSION: These findings underscore the tendency of overestimation of efficacy in early-phase trials involving immunotherapies. The observed differences could be attributed to variations in the inclusion of patients with autoimmune disorders in early-phase trials. These insights have the potential to inform stakeholders in the future development of cancer immunotherapies.

Burnout among radiology residents: a systematic review and meta-analysis.

OBJECTIVE: To analyze the prevalence of burnout among radiology residents. METHOD: Five databases (PubMed, Web of Science, Embase, PsycINFO, and Scopus) were searched for studies reporting burnout in radiology residents for the period up to November 7, 2022. RESULTS: A total of 423 studies were identified, and eventually, 16 studies were selected for the qualitative analysis, of which 11 studies were used in the meta-analysis. There was a total of 2164 radiology residents. Six studies reported the prevalence of burnout but the data could not be pooled due to their inconsistent definitions of burnout. The mean scores of three burnout subscales indicated a moderate to high degree of severity: emotional exhaustion = 25.2 (95% CI, 22.1-28.3; I2 = 94.4%), depersonalization = 10.2 (95% CI, 8.5-11.9; I2 = 93.0%), and low perception of personal accomplishment = 32.9 (95% CI, 30.5-35.4; I2 = 94.4%). The pooled prevalence of high-degree emotional exhaustion was 49.9% (95% CI, 43.6-56.1%; I2 = 55.7%), high-degree depersonalization was 45.1% (95% CI, 38.3-52.0%; I2 = 63.2%), and high-degree diminished personal accomplishment was 58.2% (95% CI, 36.0-77.6%; I2 = 84.9%). The impact of the COVID-19 pandemic on radiology residents was not investigated. In addition, there are inconsistent findings on the effects of female sex, seniority, and social support on burnout. CONCLUSIONS: About half of the radiology residents showed at least one of the three burnout manifestations (emotional exhaustion, depersonalization, and personal accomplishment), with a moderate to high degree of severity. CLINICAL RELEVANCE STATEMENT: Such a high prevalence and severity of burnout among radiology residents warrant the attention of residency program directors. KEY POINTS: • Burnout, not uncommon among radiology residents, has not been effectively analyzed. • Nearly half of the radiology residents experience at least one of the three manifestations of burnout to a moderate to high degree. • The high prevalence and severe degree of burnout among radiology residents warrant the attention of residency program directors.

Tacrolimus shows adequate efficacy in patients with antiphospholipid antibodies associated thrombocytopenia: a retrospective cohort study.

Thrombocytopenia is a common manifestation associated with the presence of antiphospholipid antibodies (aPL). The aim of this study is to investigate the efficacy and safety of tacrolimus treatment in aPL associated thrombocytopenia. This is a single-center retrospective study. Patients who had persistent positive aPL and thrombocytopenia that was treated with tacrolimus were included. A total of 49 patients [38 females (77.6%)] were enrolled from Nov 2013 to Apr 2022 with a median treatment duration of 22 months. Seventeen fulfilled classification criteria of antiphospholipid syndrome (APS), 18 systemic lupus erythematosus (SLE). The median age of study patients was 37 years (IQR 31, 48). Forty-three (87.8%) patients were on concomitant use of glucocorticoids, 6 on tacrolimus monotherapy. The overall response rate in this cohort was 85.7% (n = 42), including 49% of complete responses (n = 24). The median time to achieve a response was 3 months. Nine (18.4%) patients with overall response experienced a loss of response. The response rate during follow-up in patients with monotherapy was noninferior. Patients with positive antinuclear antibody (ANA) showed the tendency of maintaining response (p = 0.028). The 19 patients who were on medium and high dosage of glucocorticoids (> 15 mg prednisone/d) managed to taper glucocorticoids rapidly. Side effects were reported in 12.2% (n = 6) of the patients (elevated creatinine, general malaise, elevated liver enzyme). Tacrolimus has adequate efficacy, steroid-sparing effect and is well tolerated for aPL associated thrombocytopenia. Patients with positive ANA might benefit the most from tacrolimus treatment.

Serum Calprotectin as a Potential Predictor of Microvascular Manifestations in Patients with Antiphospholipid Syndrome.

INTRODUCTION: Microvascular manifestations constitute a subtype of antiphospholipid syndrome, and those patients have relatively poor prognoses, so it is important to find markers for microvascular manifestations. This study was conducted to explore whether serum calprotectin could be a predictor of microvascular manifestations in antiphospholipid antibody (aPL)-positive patients. METHODS: Consecutive patients with persistent aPL positivity referred to Peking Union Medical College Hospital and age- and sex-matched health controls (HCs) were included. Microvascular manifestations included antiphospholipid syndrome (APS) nephropathy, livedo reticularis, valvular lesions, non-stroke central nervous system manifestations, myocarditis, catastrophic APS, and other microvascular manifestations confirmed by pathology, imaging, or clinical diagnosis. Calprotectin was measured by an enzyme-linked immunosorbent assay (ELISA). The cutoff value was defined as mean + 2 standard deviations of HCs. Multivariable logistic regression analysis was used to analyze risk factors. Pearson correlation analysis was used to detect the correlation between calprotectin and other laboratory data. RESULTS: Of the 466 patients included in the study, 281 (60.3%) patients met the 2006 Sydney Revised Classification Criteria; among the latter, 77.2% were patients with primary APS. The mean age was 39.10 ± 13.05 years old, and 77.0% were female. Thirty-eight age- and sex-matched HCs were included in the study. Serum calprotectin levels were increased in aPL-positive patients compared with HCs (649.66 ± 240.79 vs 484.62 ± 149.37 ng/ml, p < 0.001), and were increased in patients with microvascular manifestations compared with patients without (693.03 ± 271.90 vs 639.43 ± 232.06 ng/ml, p = 0.044). The cutoff value was 783.36 ng/ml. Ninety-three patients (20.0%) were positive for calprotectin. Calprotectin positivity was independently associated with microvascular manifestations (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.07-3.36) and platelet count (PLT) < 100 (OR 2.04, 95% CI 1.08-3.88). Age (OR 0.98, 95% CI 0.96-1.00), systemic lupus erythematosus (OR 2.08, 95% CI 1.15-3.75), calprotectin positivity (OR 1.83, 95% CI 1.02-3.26), hypertension (OR 2.73, 95% CI 1.36-5.45), hemolytic anemia (OR 2.66, 95% CI 1.13-6.23), and anti-ß2GPI antibodies (OR 2.06, 95% CI 1.11-3.83) could independently predict microvascular manifestations in aPL-positive patients. Serum calprotectin negatively correlated with PLT (R = - 0.101, p = 0.031). CONCLUSION: Serum calprotectin levels are increased in aPL-positive patients and could be a potential predictor of microvascular manifestations.

Cluster analysis of antiphospholipid antibodies-associated adverse pregnancy outcome patients: based on a 13-years cohort study.

Antiphospholipid antibodies (aPLs) are the leading causes of adverse pregnancy outcomes (APOs). We conducted cluster analysis to identify distinct phenotypes among aPLs-associated APOs patients. This approach aims to facilitate risk stratification and improve pregnancy outcomes for obstetric APS. This was a retrospective study of persistent aPLs positive women cohort in Peking Union Medical College Hospital. Baseline demographic characteristics, clinical manifestation, previous APOs and antibodies profiles were included for hierarchical cluster analysis. Placentae from portions of patients were collected and performed the histopathologic diagnoses. Four clusters among 209 patients with 477 pregnancies were identified. Cluster 1 comprised patients with triple aPLs positivity and demonstrates a high incidence of gestational hypertension (34.92%, P < 0.05) and preterm delivery (20.63%, P < 0.05). Patients in cluster 2 were characterized by lupus anticoagulant (LA) positivity, with high risk of whole gestational APOs. Cluster 3 included patients with isolated aPLs-IgM isotype combined with early miscarriage (60.92%, P = 0.016). Patients in cluster 4 majorly presented aPLs-IgG isotype combined with placenta insufficiency (22.73%). During the follow-up, the live birth rate in cluster 1 and 2 was only 69.20%. Placenta pathology revealed the most severe impairment within cluster 1, whereas clusters 3 and 4 exhibited relatively milder damage. By cluster analysis, we identified four clinical subtypes of aPLs-associated APOs patients. Patients with triple antibodies or high-risk lupus characteristics were prone to occurred gestational hypertension and premature delivery. Isolated LA or aCL/aß2GPI positivity were found to be more frequently associated with early-stage fetal loss.

Anti-ß2GPI-domain I antibody is associated with extra-criteria manifestations in a large prospective antiphospholipid syndrome cohort in China.

BACKGROUND: Anti-ß2GPI-domain I (ß2GPI-DI) antibody is pathogenic in patients with antiphospholipid syndrome (APS), but its additional clinical associations and diagnostic value are controversial. METHODS: A total of 378 patients were included, of which 119 patients diagnosed with primary APS, 50 with APS secondary to SLE (SAPS group), 209 with SLE without APS (SLE group). Serum anti-ß2GPI-DI IgG was measured using chemiluminescent immunoassay. Extra-criteria manifestations were analysed, including thrombocytopenia, autoimmune haemolytic anaemia, valvular lesions, APS nephropathy and non-vascular neurological manifestations. RESULTS: In 169 patients with APS, 55 (32.5%) were positive for anti-ß2GPI-DI IgG, accounting for 77.5% of those with anti-ß2GPI IgG positivity. It is shown that 96.4% of those with anti-ß2GPI-DI IgG also showed triple positivity in classic antiphospholipid antibodies (aPLs). The positivity of anti-ß2GPI-DI IgG was significantly associated with recurrent thrombosis before APS diagnosis (p=0.015), microvascular thrombosis (p=0.038), but not with pregnancy morbidity (PM). Notably, patients with extra-criteria manifestations showed significantly higher positivity (p=0.001) and titres (p<0.001) in anti-ß2GPI-DI IgG, especially for thrombocytopenia and APS nephropathy. In multivariable analysis, anti-ß2GPI-DI IgG positivity (OR 2.94, 95% CI 1.29 to 6.70), secondary APS, arterial hypertension and Coombs' test positivity independently predicted extra-criteria manifestations (C-index 0.83, 95% CI 0.77 to 0.90). After a median follow-up of 25 months, patients with anti-ß2GPI-DI IgG also showed a tendency of more extra-criteria events, but not thrombotic events. Anti-ß2GPI-DI was positive among 8.1% of the SLE controls, and showed high specificity (91.9%) in diagnosing SAPS among patients with SLE as compared with classic aPLs. CONCLUSION: Anti-ß2GPI-DI IgG was associated with extra-criteria manifestations in patients with APS. Further studies are warranted to validate its predictive values and potential role in daily practice.

The prevalence of burnout among pulmonologists or respiratory therapists pre- and post-COVID-19: a systematic review and meta-analysis.

OBJECTIVES: The coronavirus disease-19 (COVID-19) increased the already heavy workload in the pulmonary and respiratory departments, which therefore possibly increased the prevalence of burnout among pulmonologists or respiratory therapists. We aimed to compare the differences in burnout among pulmonologists or respiratory therapists pre- and post-COVID-19 by doing a systematic review with meta-analysis. METHODS: We searched pulmonologist, or pulmonary, or respiratory, and burnout up to 29 January 2023 in six databases. We included studies investigating pulmonologists or respiratory therapists and reporting the prevalence of burnout among them. The risk of bias was assessed by a tool for prevalence studies. The overall prevalence of burnout was pooled. RESULTS: A total of 2859 records were identified and 16 studies were included in the final analysis. The included studies reported 3610 responding individuals and 2336 burnouts. The pooled prevalence of burnout was 61.7% (95% confidence interval (CI), 48.6-73.2%; I2 = 96.3%). The pooled prevalence of burnout during COVID-19 was significantly higher than it was prior to the outbreak (68.4% vs. 41.6%, p = .01). The result of the meta-regression revealed that COVID-19 coverage was significantly associated with the prevalence of burnout (p = .04). CONCLUSIONS: Burnout was widely prevalent among pulmonologists or respiratory therapists and increasingly perceived during COVID-19. Therefore, interventions were needed to reduce burnout in this specialty.KEY MESSASGESThe coronavirus disease-19 increased the already heavy workload in the pulmonary and respiratory departments.Burnout was widely prevalent among pulmonologists or respiratory therapists and increasingly perceived during COVID-19.

Validation of three prediction models for thrombosis recurrence in antiphospholipid syndrome patients based on a prospective cohort.

OBJECTIVES: To validate the performance of the adjusted global antiphospholipid syndrome (APS) score (aGAPSS), Padua score and Caprini score to predict thrombosis recurrence in APS. METHODS: Consecutive thrombotic-APS patients were included. aGAPSS, Padua and Caprini score at baseline were collected. Harrell c-index and calibration curve were used to validate the prediction models. RESULTS: 362 patients were enrolled. The mean age was 36.30±13.88 years old, and 209 (57.7%) were female. Patients were followed up for a median of 2.32 years, with 32 (8.84%) venous and 21 (5.80%) arterial thrombosis. The 1-year, 3-year and 5-year thrombosis risks were 5.0%, 14.3% and 17.9%, respectively. The Harrell c-indexes of aGAPSS, Padua and Caprini score were 0.54 (95% CI 0.44 to 0.64), 0.54 (95% CI 0.46 to 0.62), and 0.50 (95%CI 0.42 to 0.58), respectively. Padua score had the best discrimination to predict venous thrombosis (Harrell c-index=0.61, 95% CI 0.53 to 0.69). aGAPSS had the best discrimination to predict arterial thrombosis (Harrell c-index=0.61, 95% CI 0.47 to 0.75). The calibrations for predicting thrombosis within 1, 3 and 5 years of the three models were suboptimal. CONCLUSION: The performance of aGAPSS, Padua and Caprini score to predict thrombosis recurrence in APS were suboptimal. Arterial and venous thrombosis recurrence predictors were different. New prediction models are required for venous and arterial thrombosis separately.

Associations of low-carbohydrate with mortality in chronic kidney disease.

BACKGROUND: Diet management is an effective way to retard the progression of chronic kidney disease (CKD). However, very few studies investigated the influence of carbohydrate intake on CKD patients. In this prospective cohort study, the associations between carbohydrate intake and all-cause mortality were investigated in US adult CKD patients. METHODS: Multivariable Cox proportional hazard models and iso-caloric replacement analysis were used to investigate the associations between the macronutrients and the all-cause mortality risk. Total 3683 US adult CKD patients 20 years or older from the National Health and Nutrition Examination Survey (NHANES, 2003-2014) were analyzed (mean age ± SD, 62.4 ± 17.1; 56.5% female), of which 1082 participants with CKD died with a median follow-up time of 67 (IQR 36-99) months. RESULTS: Most macronutrients were non-linearly associated with all-cause mortality risk, including carbohydrates and sugar. Participants with CKD had lower mortality risk when consuming 30-45% energy from carbohydrates (average HR 0.76, 95%CI 0.62-0.93, compared with 60%), 5-20% energy from sugar (average HR 0.75, 95% CI 0.59-0.96 compared with 40%). Replacing the energy intake from carbohydrates with protein (up to 30%) and/or replacing the sugar with non-sugar carbohydrates (up to 55%) reduced the all-cause mortality risk, while the total energy intake remained constant. CONCLUSIONS: Diet advice should be given according to the current diet status, and constituents of carbohydrates should also be taken into consideration.

Do intravitreal anti-vascular endothelial growth factor agents lead to renal adverse events? A pharmacovigilance real-world study.

Purpose: Intravitreal vascular endothelial growth factor (VEGF) blockade is essential in many macular edema diseases treatment. However, intravitreal VEGF treatment has been reported to lead to deteriorated proteinuria and renal function. This study aimed to explore the relationship between renal adverse events (AEs) and the intravitreal use of VEGF inhibitors. Method: In the FDA's Adverse Event Reporting System (FAERS) database, we searched for renal AEs of patients receiving various anti-VEGF drugs. We performed statistics on renal AEs in patients treated with Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab (from January 2004 to September 2022) using disproportionate and Bayesian analysis. We also investigated the time to onset, fatality, and hospitalization rates of renal AEs. Results: We identified 80 reports. Renal AEs were most frequently associated with Ranibizumab (46.25%) and Aflibercept (42.50%). However, the association between intravitreal anti-VEGFs and renal AEs was insignificant since the reporting odds ratio of Aflibercept, Bevacizumab, Ranibizumab, and Brolucizumab were 0.23 (0.16, 0.32), 0.24 (0.11, 0.49), 0.37 (0.27, 0.51) and 0.15 (0.04, 0.61), respectively. The median time to renal AEs onsets was 37.5 (interquartile range 11.0-107.3) days. The hospitalization and fatality rates in patients who developed renal AEs were 40.24 and 9.76%, respectively. Conclusion: There are no clear signals for the risk of renal AEs following various intravitreal anti-VEGF drugs based on FARES data.