Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial.

BACKGROUND: Chronic headache is a 'silent' neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches. METHODS AND ANALYSIS: SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement. ETHICS AND DISSEMINATION: Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05613582.

Association between Proinflammatory Cytokines and Anxiety and Depression Symptoms in Rheumatoid Arthritis Patients: A Cross-sectional Study.

Background: Rheumatoid arthritis (RA) patients have a greater prevalence of anxiety and depression. Proinflammatory cytokines are elevated in RA. We aim to evaluate the association between systemic inflammation in RA and anxiety and depression. Methods: There were 31 RA patients, 16 with active disease activity and 15 in remission state; they were assessed using the Hospital Anxiety and Depression Scale and for RA disease activity using Disease Activity Score of 28 joints (DAS28) - CRP (C-reactive protein). Serum proinflammatory cytokines were measured, including interleukin (IL)-6, IL-17, and Tumour Necrosis Factor-alpha (TNF-α). Results: Among 31 patients, ten patients showed anxiety symptoms, 19 patients showed depression symptoms, and two displayed mixed symptoms. Serum TNF-α levels were significantly higher in active disease than in the remission group (p-value 0.006). There was no association or correlation between proinflammatory cytokines to anxiety and depression symptoms in the active disease and remission groups. Conclusion: This suggests that other factors besides disease activity and state of systemic inflammation may cause anxiety and depression in RA patients.

Learning from the COVID-19 pandemic: health care disturbances and telemedicine as an alternative rheumatology practice in Indonesia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) affects health care services. Our aim was to assess health care disruptions, treatment interruptions, and telemedicine reception regarding autoimmune rheumatic diseases (ARDs) in Indonesia. METHOD: A cross-sectional population online-based questionnaire was conducted in Indonesia from September to December 2021. RESULTS: A total of 311 ARD patients were included, of whom 81 (26.0%) underwent consultations via telemedicine during the COVID-19 pandemic. The respondents showed increased concern about their susceptibility to COVID-19 (score of 3.9/5). Approximately 81 (26.0%) avoided hospital visits, and 76 (24.4%) stopped taking the medication without medical advice. Respondents' concerns correlated with their social distancing behaviors (p value 0.000, r 0.458). Respondent concerns, behaviors, and blocked access to the hospital during the pandemic were associated with avoiding hospital visits (p value 0.014; 0.001; 0.045; 0.008). Sex was associated with stopping medication (p value 0.005). In multivariate analysis, blocked access and sex remained significant. Approximately 81 (26%) respondents who used telemedicine services during the COVID-19 pandemic as an alternative medical consultation method showed high satisfaction (3.8/5). CONCLUSION: Health care disruptions and treatment interruptions were affected by patients' internal and external factors during the COVID-19 pandemic. Telemedicine may be the best option to address barriers to health care access in Indonesia's rheumatology practice during and after the pandemic situation.

Predisposing Factors of Tuberculosis Infection in Systemic Lupus Erythematosus Patients: A Single-Center Case-Control Study.

INTRODUCTION: Indonesia has the second-highest tuberculosis cases in the world, according to the global WHO tuberculosis report, amounting to approximately 10% of the world's tuberculosis cases. Systemic lupus erythematosus (SLE) patients are at an increased risk for tuberculosis infection. This research aims to analyze the association between corticosteroid pulse dose, corticosteroid cumulative dose, SLE disease duration, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and lupus nephritis status with the development of tuberculosis in SLE patients. METHODS: This research was a matched case-control study to identify risk factors of tuberculosis infection in SLE patients. Data were taken from medical records of Cipto Mangunkusumo National General Hospital, a national tertiary hospital. Inclusion criteria were patients who meet the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria of SLE in the period of 2012-2016 or patients who meet the SLICC 2012 SLE criteria and developed tuberculosis between 2012 and 2016. Statistical analyses used were bivariate analysis and correlation analysis. All statistical analyses were conducted using SPSS software (IBM Corp., Armonk, NY). All statistical analyses were defined as statistically significant when the p-value was less than 0.05. RESULTS: A total of 48 SLE patients were included from medical records consisting of 24 SLE patients with tuberculosis infection and controls of 24 SLE patients without tuberculosis infection. In this study, it was observed that the presence of lupus nephritis (p = 0.001), administration of pulse corticosteroids (p = 0.048), high corticosteroid cumulative dose (p = 0.001), and high SLEDAI score (p = 0.003) were associated with tuberculosis infection. Correlation analysis showed that all of these variables had a weak positive correlation with tuberculosis infection in SLE patients. CONCLUSION: SLE patients with lupus nephritis, administration of pulse corticosteroids, high cumulative corticosteroid dose, and high SLEDAI score have a higher risk of tuberculosis infection. Clinicians and patients should be aware of these risk factors in SLE patients to prevent tuberculosis infection. Corticosteroid pulse dose should be avoided in SLE patients and if it is needed, tuberculosis prophylaxis may be considered.

Factors Associated With Candidiasis in Systemic Lupus Erythematosus Patients in Cipto Mangunkusumo National General Hospital: A Single-Center Case-Control Study.

BACKGROUND: Infection has been a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. One of the infections encountered in SLE patients is candidiasis. Therefore, we aimed to conduct a case-control study to explore the risk factors associated with candidiasis in SLE patients in our center. METHODS: Medical records of 20 SLE patients with fungal infection were obtained, and a case-control study was conducted with an age and sex-matched control group of 20 patients. Data were obtained from the Cipto Mangunkusumo National General Hospital. SLE confirmatory diagnosis was based on Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. Patients with comorbidities of various chronic diseases (diabetes, HIV, and chronic kidney disease) were excluded. Statistical analysis was conducted using the Mann-Whitney U test with statistical significance defined as a p-value < 0.05. RESULT: Based on the analysis, a maximum corticosteroid dose of 24 (4-250) mg/day for the last one year was associated with the development of fungal infection (p = 0.047). Lower absolute lymphocyte count (748 cells/mm³ versus 1635 cells/mm³) was also associated with the occurrence of candidiasis in SLE patients (p = 0.008). CONCLUSION: Physicians should be aware that corticosteroid use in SLE patients may cause candidiasis. Monitoring of maximum corticosteroid dose and absolute lymphocyte count is important to help prevent candidiasis. Patients should also be educated regarding the risk of candidiasis from corticosteroid use.

Correlation between serum methotrexate-polyglutamate 3 (MTX-PG3) level and disease activity in rheumatoid arthritis patients: A prospective cohort study.

Background: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, characterized by systemic inflammation, joint destruction and disability. Methotrexate (MTX) is used as the primary treatment for RA patients. However, the response to MTX therapy is highly varied and difficult to predict. This study sought to determine the role of MTX by measuring the MTX polyglutamate 3 (MTX-PG3) levels and the disease activity score 28 based on C-reactive protein (DAS28-CRP) of RA patients. Method: A prospective cohort study was conducted at the Rheumatology Polyclinic of Dr. Cipto Mangunkusumo General Hospital. Thirty-four patients with RA were included and followed up to 12 weeks. The RA patients were treated with MTX 10 mg per week and an increased dose of 5 mg per week every month. DAS28-CRP and MTX-PG3 level were assessed at week 8 and 12. Multivariate logistic regression analysis was used to determine the correlation between MTX-PG3 and DAS28-CRP. Result: A total of 34 RA patients were followed and the MTX was well tolerated in which no increase of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and glomerular filtration rate (GFR) were observed. The mean scores of DAS28-CRP decreased following the MTX-treatment: 3.93, 3.22 and 2.82 at week 0, 8 and 12, respectively. In contrast, the median concentration of MTX-PG3 increased from week 8 to week 12 followed by increasing the dose of MTX. Our analysis suggested there was a moderate positive correlation between MTX-PG3 levels and DAS28-CRP score at week 8 and week 12 post-MTX treatment. Conclusion: The level of MTX-PG3 is correlated with DAS28-CRP score suggesting that MTX-PG3 could be used as an indicator to assess the disease activity in RA patients. Nevertheless, a prospective study with a higher number of patients is needed to confirm this finding.

Xanthine Oxidase-Induced Inflammatory Responses in Respiratory Epithelial Cells: A Review in Immunopathology of COVID-19.

Xanthine oxidase (XO) is an enzyme that catalyzes the production of uric acid and superoxide radicals from purine bases: hypoxanthine and xanthine and is also expressed in respiratory epithelial cells. Uric acid, which is also considered a danger associated molecule pattern (DAMP), could trigger a series of inflammatory responses by activating the inflammasome complex path and NF-κB within the endothelial cells and by inducing proinflammatory cytokine release. Concurrently, XO also converts the superoxide radicals into hydroxyl radicals that further induce inflammatory responses. These conditions will ultimately sum up a hyperinflammation condition commonly dubbed as cytokine storm syndrome (CSS). The expression of proinflammatory cytokines and neutrophil chemokines may be reduced by XO inhibitor, as observed in human respiratory syncytial virus (HRSV)-infected A549 cells. Our review emphasizes that XO may have an essential role as an anti-inflammation therapy for respiratory viral infection, including coronavirus disease 2019 (COVID-19).

Septic Pulmonary Embolism Following Appendectomy Surgery.

Septic Pulmonary embolism is a rare condition where there were numerous pulmonary infarcts resulting from blood clot emboli that also contains microorganism. This disorder is insidious onset, Its clinical features usually unspecific and the diagnosis usually difficult to establish. A 43 old woman who underwent an appendicitis surgery, reentered the hospital at the sixth day after surgery presented with fever, pain at the surgical site, progressive severe dyspnea and chest tightness. From the physical examination finding there were tachycardia, tachypneu, wet rough basal rhonki on the right rear and tenderness at right lower region of the abdomen. The thorax-abdomen CT scan result was pleuropneumonial with minimal effusion in the right side. A CT angiography scan of the chest and abdomen showed intralumen emboli in medial lobe segmen of right pulmonary artery, right pleuropneumonia with segmental lession in segmen 10 right lobe and inflammation process along right lateral wall of the abdomen. Laboratory results that also supported diagnosis were D dimer 3442 ng/mL and culture result from surgical site pus showed E. Coli ESBL (+). Base on these findings, this case was established as a septic pulmonary embolism.