Objective
Diffuse alveolar haemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). We describe the clinical characteristics, treatment and survival ...outcomes of SLE patients with DAH in Singapore.
Methods
We conducted a retrospective review of the medical records of SLE patients with DAH hospitalised in 3 tertiary hospitals between January 2007 and October 2017. Patient demographics, clinical characteristics, laboratory, radiologic and bronchoscopic findings, as well as the treatments, were compared between survivors and non-survivors. Survival rates were analysed between the various treatment groups.
Results
A total of 35 patients with DAH were included in this study. Majority of them were female (71.4%) and of Chinese ethnicity (62.9%). Median age was 40.0 years (IQR: 25–54), with a median disease duration of 8.9 months (IQR: 0.13–102.4). Haemoptysis was the most common clinical presentation, and majority had concomitant cytopaenia and lupus nephritis. All patients received high dose glucocorticoids; 27 (77.1%), 16 (45.7%) and 23 (65.7%) received cyclophosphamide (CYP), rituximab (RTX), and plasmapheresis (PLEX), respectively. Twenty-two patients required mechanical ventilation with a median duration of 12 days. Overall mortality rate was 40%, with a median survival time of 162 days. Twenty-six patients (74.3%) achieved remission, with an overall median time to remission of 12 days (IQR: 6–46) after diagnosis of DAH. Patients on triple therapy (CYP, RTX and PLEX) had a median survival of 162 days as compared to 14 days in patients on PLEX alone (p = .0026).
Conclusions
The overall mortality of DAH in SLE patients remained high. There were no significant differences in patient demographics or clinical characteristics between the survivors and non-survivors. However, better survival appears to be associated with treatment with cyclophosphamide.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aims
To identify pre‐treatment risk factors for the development of Palmar Plantar Erythrodysesthesia in participants receiving capecitabine monotherapy. Specifically the hypothesis that avoidance of ...activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia was tested.
Background
Previous literature showed contradictory evidence on the subject of predictors of chemotherapy‐induced Palmar Plantar Erythrodysesthesia. There is a lack of empirical evidence to support the theory that Palmar Plantar Erythrodysesthesia is caused by damage to the microcapillaries due to everyday activities that cause friction or pressure to the hands or feet.
Design
Prospective epidemiological study of risk factors.
Methods
Prospective data collection. All patients prior to commencing capecitabine monotherapy between 11 June 2009–31 December 2010, were offered recruitment into the study and followed up for six cycles of treatment (n = 174). Data were collected during semi‐structured interviews, from participants' diaries, physical examination of the hands and feet and review of notes. Data relating to activities that cause friction, pressure or heat were collected.
Data were analysed using bivariate (chi‐square and independent groups Student's t) tests where each independent variable was analysed against Palmar Plantar Erythrodysesthesia.
Results
The only variables that were associated with an increased risk of Palmar Plantar Erythrodysesthesia were a tendency to have warm hands and pre‐existing inflammatory disease.
Conclusions
This study gives no support for the hypothesis that avoidance of activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia.
We recently reported that messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination was associated with flares in 9% of patients with systemic lupus erythematosus (SLE). ...Herein, we focused our analysis on patients from a multi-ethnic Southeast Asian lupus cohort with the intention of identifying distinct phenotypes associated with increased flares after mRNA COVID-19 vaccination.
Six hundred and thirty-three SLE patients from eight public healthcare institutions were divided into test and validation cohorts based on healthcare clusters. Latent class analysis was performed based on age, ethnicity, gender, vaccine type, past COVID-19 infection, interruption of immunomodulatory/immunosuppressive treatment for vaccination, disease activity and background immunomodulatory/immunosuppressive treatment as input variables. Data from both cohorts were then combined for mixed effect Cox regression to determine which phenotypic cluster had a higher risk for time to first SLE flare, adjusted for the number of vaccine doses.
Two clusters were identified in the test (C1 vs. C2), validation (C1' vs. C2') and combined (C1″ vs. C2″) cohorts, with corresponding clusters sharing similar characteristics. Of 633 SLE patients, 88.6% were female and there was multi-ethnic representation with 74.9% Chinese, 14.2% Malay and 4.6% Indian. The second cluster (C2, C2' and C2″) was smaller compared to the first. SLE patients in the second cluster (C2 and C2') were more likely to be male, non-Chinese and younger, with higher baseline disease activity. The second cluster (C2″) had more incident flares (hazard ratio = 1.4, 95% confidence interval 1.1-1.9,
= 0.014) after vaccination. A higher proportion of patients in C2″ had immunomodulatory/immunosuppressive treatment interruption for vaccination as compared to patients in C1″ (6.6% vs. 0.2%) (
< 0.001).
We identified two distinct phenotypic clusters of SLE with different patterns of flares following mRNA COVID-19 vaccination. Caution has to be exercised in monitoring for post-vaccination flares in patients with risk factors for flares such as non-Chinese ethnicity, young age, male gender and suboptimal disease control at the time of vaccination.
To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ...spondyloarthritis (SpA).
A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI).
Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA.
About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.
Background The development of lupus low disease activity state (LLDAS) as a treat-to-target endpoint for SLE patients has been validated. Its attainment has been associated with improved outcomes. ...This study aims to show whether a machine learning model can yield good results in predicting whether a patient will achieve LLDAS on their succeeding assessment. Methods A total of 42,355 records of patients were retrieved from the APLC longitudinal study database. Three machine learning models – XGBoost, Random Forest, and Naive Bayes – were tested for their predictive power. Eighty percent of the data was used to train the models while thirty percent was used for validation. The data were normalized and all models were subjected to 10-fold cross-validation to prevent overfitting. Additionally, we compared the top ten most significant features of each model. Results Various metrics were used to measure the model’s predictive power. The results of our study showed that the Random Forest model scored the highest for specificity, PPV, and accuracy with 0.8450, 0.8182, and 0.8338, respectively. The XGBoost model topped the NPV metric with 0.8559 while the Naive Bayes model got the highest score for sensitivity with 0.8986. It is good to note that the score difference of Random Forest with the top sensitivity and NPV scores were only 0.0629 and 0.0085, respectively. For the significant features, only two features were present on all three models, namely the current LLDAS and proteinuria level. Three additional features were important for two models—whether the patient is taking prednisolone; time adjusted mean (TAM) SLEDAI score; and SLEDAI score. Conclusions The study showed and compared various machine learning models on their predictive power in determining whether a patient will achieve LLDAS on their next visit. The results determined that the current LLDAS, proteinuria levels, SLEDAI score (and TAM SLEDAI),
Assess whether treatment with probiotics improve gastrointestinal symptoms in patients with systemic sclerosis (SSc).
In this double-blind randomized placebo-controlled parallel-group phase II trial, ...SSc subjects with total score ≥ 0.1 on a validated SSc-specific gastrointestinal tract (GIT) questionnaire were randomized (1:1) to receive 60 days of high dose multi-strain probiotics (Vivomixx® 1800 billion units/day) or identical placebo, followed by an additional 60 days of probiotics in both groups. Between group differences in GIT score change were assessed after 60 days (primary outcome, time-point T1) and 120 days (secondary outcome, time-point, T2) by an intention-to-treat approach. Stool samples at three time-points were subjected to 16S next generation sequencing.
Forty subjects were randomized to placebo-probiotics (n = 21) or probiotics-probiotics (n = 19). At T1, no significant improvement was observed between the two groups, reported as mean ± SE for total GIT score (placebo 0.14 ± 0.06 versus probiotics 0.13 ± 0.07; p = 0.85) or its subdomains. At T2, whilst there was no significant improvement in total GIT score (placebo-probiotics –0.05±0.06; probiotics-probiotics –0.18 ± 0.07; p = 0.14), there was significant improvement of GIT-reflux in the probiotic group (–0.22 ± 0.05 versus placebo-probiotics 0.05 ± 0.07; p = 0.004). Subjects on probiotics exhibited increasing stool microbiota alpha diversity compared to the placebo-probiotics group. Adverse events (AEs) were mild, with similar proportion of subjects with AEs and serious AEs in both groups.
Whilst there was no clear improvement in overall GI symptoms after 60 days, we observed significantly improved GI reflux after 120 days of probiotics. The trial confirmed safety of multi-strain probiotics in SSc patients. Trial registration. Clinicaltrials.gov; NCT01804959
Objective
To determine the efficacy of CXCL5 administration in lupus‐prone MRL/lpr (Faslpr) mice and elucidate its working mechanisms.
Methods
CXCL5 expression in blood (obtained from SLE patients ...and Faslpr mice) and major internal organs (obtained from Faslpr mice) was examined by Luminex, real‐time polymerase chain reaction, and immunofluorescent staining analyses. Pharmacokinetic studies were performed in Faslpr mice and healthy Institute of Cancer Research mice. Efficacy of CXCL5 administration was demonstrated in Faslpr mice, and the working mechanism of CXCL5 treatment was elucidated by flow cytometry, Luminex, and RNA sequencing.
Results
In SLE patients, serum CXCL5 levels were significantly lower than in healthy individuals (P < 0.0001) and negatively correlated with disease activity (P = 0.004). In Faslpr mice, disease severity progressed with age and was negatively associated with plasma CXCL5 levels. Intravenous administration of CXCL5 to Faslpr mice restored endogenous circulatory CXCL5, improved mice survival, and reduced anti–double‐stranded DNA antibodies, proteinuria, lupus nephritis activity and chronicity indices, renal complements, and neutrophil extracellular traps over short‐term (10 weeks) and long‐term (2 years) time periods. In vitro and in vivo assays demonstrated that CXCL5 dictated neutrophil trafficking and suppressed neutrophil activation, degranulation, proliferation, and renal infiltration. Renal and splenic RNA sequencing further showed that CXCL5‐mediated immunomodulation occurred by promoting energy production in renal‐infiltrated immune cells, activating certain T cells, and reducing tissue fibrosis, granulocyte extravasation, complement components, and interferons. Further factorial design results indicated that CXCL5 appears to enhance host tolerability to cyclophosphamide in vulnerable individuals.
Conclusion
We found that serum CXCL5 levels were significantly lower in SLE patients than in healthy individuals and were negatively correlated with disease activity. By administering CXCL5 intravenously in a mouse model of lupus, mouse survival improved, and indices of disease activity reduced significantly. Taken together, these findings indicate CXCL5 administration may represent a novel myeloid/neutrophil‐targeting therapy for SLE.
Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated ...measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive.
Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare.
Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio HR 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009).
Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.
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