Methotrexate Increases Serum Calcium Levels in Patients with Rheumatoid Arthritis: A Retrospective Study at a Referral Hospital in Indonesia.

Background: Rheumatoid arthritis (RA) is a significant issue, particularly in bone health problems, because it can prolong diseases like secondary osteoporosis. Subsequently, the anchor of drug therapy for RA is methotrexate (MTX), which also has the potential to reduce the risk of secondary osteoporosis. Objective: This study aims to examine the effect of MTX on calcium levels, an important parameter for monitoring bone health and the risk of secondary osteoporosis in patients with RA. Methods: A retrospective study was carried out by collecting data from the medical records of patients, which included demographic and patient characteristics, treatment data (drug and dosage), duration of treatment, and calcium levels. All patients were diagnosed with RA and fell within the age range of 18 to 59 years. Additionally, the effectiveness of MTX therapy was compared with other treatments, categorizing patient data accordingly. Statistical analyses, such as χ2 and ordinal regression, using IBM-SPSS Statistics version 25 (IBM-SPSS Inc, Armonk, New York) were used to establish associations between MTX treatment and calcium levels, reporting odds ratio and 95% CI values. Results: The data consisted of 123 patients with RA, comprising 99 who had a history of MTX use for more than 6 months and 24 who either did not use MTX or used it for <6 months. The majority of patients were women and their ages ranged between 40 and 59 years. MTX monotherapy was the most used with a dose range of 7.5 to 15 mg. Furthermore, this study observed that patients treated with MTX between 7.5 and 15 mg have lower serum calcium levels than those who received 17.5 to 25 mg (P = 0.022; odds ratio = 5.663; 95% CI, 0.251-3.218). Most patients with RA using MTX maintained normal calcium levels. No significant differences were observed between single MTX therapy and combination therapy. Conclusions: Although further investigation is needed, this study showed the potential properties of MTX in maintaining patients' serum calcium levels, which may help to reduce the risk of secondary osteoporosis in patients with RA.

Comparison of clinical presentation and outcome of childhood-onset and adulthood-onset of systemic lupus erythematosus among Indonesian patients.

INTRODUCTION: The clinical presentation of childhood-onset systemic lupus erythematosus (SLE) is generally perceived to differ from that of adult-onset SLE. OBJECTIVE: We aimed to compare the demographic and clinical manifestation between childhood-onset vs. adult-onset SLE in a cohort of Indonesian patients at tertiary care centers. METHODS: This retrospective study included patients in the Hasan Sadikin Lupus Registry from 2008 until December 2017. The demographics, clinical presentations, and outcomes were compared between childhood-onset SLE (<18 years old) (Group 1) and adult-onset SLE (≥18 years old) (Group 2). RESULTS: Eight hundred seventy patients were involved into this study. The proportion of childhood-onset SLE was 20% (174 patients). The mean age of group 1 versus group 2 was 13.56 ± 3.04 vs 30.41 ± 8.54 years. The following clinical manifestations at SLE diagnosis were significantly more common in childhood-onset than in adult-onset SLE patients: hematological disorder (p = 0.033) and arthritis (p = 0.006). While discoid rash (p = 0.036) and photosensitivity (p < 0.001) were significantly found higher in adult-onset SLE. Cyclophosphamide therapy was significantly more common to be used in childhood-onset (38.5% vs 21.0%, p = <0.001). However, frequency of mortality on follow-up tended to be higher in childhood-onset group (11.5% vs 7.0%, p = 0.208). CONCLUSION: Arthritis and hematologic involvements at SLE diagnosis were more prominent in childhood-onset compared to adult-onset patients, and mortality in childhood-onset SLE during follow-up relatively higher. This data may suggest the need for more aggressive management approach to childhood-onset patients with SLE.

Correlation between Interstitial Lung Disease Morphology Scores Based on High-resolution Computed Tomography Chest and Skin Fibrosis Degree Based on Modified Rodnan's Skin Score on Systemic Sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a systemic autoimmune disease involving a multisystem. Modified Rodnan's Skin Score (MRSS) is a gold standard for measuring skin fibrosis in SSc. In SSc, lung fibrosis disorders, especially interstitial lung disease (ILD), are the leading cause of mortality and often late in diagnosis. High-Resolution Computed Tomography (HRCT) Chest scan is a gold standard for evaluating ILD morphology, but its availability is limited. The degree of skin fibrosis based on MRSS in SSc can predict the presence of ILD in several studies but has not been widely studied in Indonesia. This study aimed to determine the relationship of the ILD morphology based on thoracic HRCT scan with the degree of skin fibrosis based on MRSS in SSc. METHODS: This study is a retrospective analytic observational study with a cross-sectional design. The subjects of this study are SSc patients who had data of MRSS and HRCT chest scan from July 2019 to March 2020. Statistical analysis uses Spearman's correlation test. RESULTS: There were 42 study subjects, consisting of 41 women (97.6%) and one man (2.4%) with an average age of 39.50 years old (age range of 19 years to 60 years old). Correlation test results based on Spearman's show a moderate correlation between the morphological score of ILD with MRSS with R = 0.429, which is significant (p = 0.005). CONCLUSION: There is a significant moderate correlation between the morphological scores of ILD based on HRCT chest and the degree of skin fibrosis based on MRSS in SSc.

A Double-blind, Randomized Controlled Trial of Ciplukan (Physalis angulata Linn) Extract on Skin Fibrosis, Inflammatory, Immunology, and Fibrosis Biomarkers in Scleroderma Patients.

BACKGROUND: scleroderma is an autoimmune disease characterized by organ fibrosis, resistant to standard treatment. It is suspected the addition of Physalis angulata Linn. (Ciplukan) extract as adjuvant therapy can improve the scleroderma skin fibrosis. The aim at this study is to evaluate the effect of ciplukan extract as adjuvant on scleroderma skin fibrosis in standard therapy, based on modified Rodnan skin scale (MRSS), inflammatory biomarkers, immunology and serum fibrosis. METHODS: double-blind, randomized clinical trial was performed in scleroderma patients with stable disease at Cipto Mangunkusumo hospital and Hasan Sadikin hospital during November 2015-March 2017 who met the selection criteria and continued to receive standard therapy. The subjects were randomly allocated into two groups: the study group received the ciplukan  extract 3 x 250 mg / day for 12 weeks and the placebo group. Examination of MRSS, ESR, P1NP, BAFF and sCD40L was performed every 4 weeks until the end of the study. RESULTS: fifty-nine subjects completed the study. They consisted of 29 subjects of the treatment group and 30 of the placebo group, with an average age of 41 (SD 9) years, the proportion of women: male = 9 : 1. There was a significant improvement of skin fibrosis in the study group with a highly significant decrease in MRSS (35.9% VS 6.3%, p <0.001) and a relative decrease in P1NP levels (17.8% VS 0.7%, p = 0.002). No decrease in ESR, BAFF and sCD40L levels in both groups. There was a weak but significant positive correlation between MRSS with P1NP levels (r = 0.236, p = 0.036). CONCLUSION: Ciplukan extract with dose 3 x 250 mg for 12 weeks as adjuvant on scleroderma standard therapy alleviates skin fibrosis significantly based on MRSS and P1NP levels.

Antioxidant, Antiinflammation, and Antifibrotic Activity of Ciplukan (Physalis angulata L). Extract.

Purpose: Physalis angulata Linn. (Ciplukan) is a plant widely used in traditional medicine in subtropical and tropical regions. Most studies focus on its antioxidant and anti-inflammatory activity. Many studies also reported its therapeutic potential for treating cancer, malaria, hepatitis, rheumatism, liver problems, and tumors, but few studies have reported its anti-fibrosis activity. Here, we aimed to investigate the potential of P. angulata as an antioxidant and anti-inflammatory that may be correlated with its anti-fibrosis action. Methods: In our study, we treated 3T3-L1 and TGF-ß-induced 3T3-L1 cells with an ethanol extract of P. angulata. We then monitored the cell's response, evaluated the antioxidant activity using an MTT assay, and observed the cells' migration using the cell scratch assay. We used RT-PCR to determine the expression of HIF-1α and IL-6 on TGF-ß-induced 3T3-L1 cells. Results: The ethanol extract of P. angulata showed antioxidant activity and promoted cell proliferation on 3T3-L1 cells. Interestingly, the extract inhibited the migration of TGF-ß-induced 3T3-L1 cells. Further analysis revealed that the extract could inhibit HIF-1α expression and suppress IL-6 expression on TGF-ß-induced 3T3-L1 cells. Conclusion: The ethanol extract of P. angulata showed antioxidant and anti-inflammation activities in 3T3-L1 cells. Both activities are associated with the antifibrotic activity of P. angulata's ethanol extract.

The role of neutrophyl lymphocyte count ratio as an inflammatory marker in systemic lupus erythematosus.

AIM: to evaluate neutrophyl lymphocyte count ratio (NLCR) as an inflammatory marker in systemic lupus erythematosus (SLE). METHODS: this was a cross sectional study involving 21 SLE patients with mild and moderate disease activity according to Mex SLEDAI score and 30 normal subjects. White blood cells counts were examined with Sysmex XE-5000. The absolute neutrophyl count and absolute lymphocyte count were tabulated and compared between SLE and normal subjects using unpaired t-test. The comparison of NLCR between SLE and normal subject was calculated using Mann-Whitney test. This study was conducted in the Department of Internal Medicine Hasan Sadikin Hospital from November 2011 until January 2012. RESULTS: there was no significant difference in absolute neutrophyl count between SLE and normal subjects (4158+1517 vs 4031+1218 /mm3, p=0.74). The absolute lymphocyte count was significantly lower in SLE than normal subjects (1721+600 vs 2397+587/mm3, p=0.000). NLCR was significantly higher in SLE than normal subjects (2.52 (1.01-10.92) vs 1.65 (0.77-4.59), p=0.007). There was no significant difference in NLCR between SLE with mild and moderate activity (2.59 (1.01-10.92) vs 2.01 (1.38-3.98), p= 0.412). Based on ROC curve, with AUC 0.727, cut off NLCR value >1.93 had 70% sensitivity and 67% specificity in differentiating between SLE and normal subjects. CONCLUSION: NLCR could be used as simple inflammatory parameter in SLE.

The Kynurenine/Tryptophan Ratio as a Promising Metabolomic Biomarker for Diagnosing the Spectrum of Tuberculosis Infection and Disease.

The metabolic system and immunology used to be seen as distinct fields of study. Recent developments in our understanding of how the immune system operates in health and disease have connected these fields to complex systems. An effective technique for identifying probable abnormalities of metabolic homeostasis brought on by disease is metabolomics, which is defined as the thorough study of small molecule metabolic intermediates within a biological system that collectively make up the metabolome. A prognostic metabolic biomarker with adequate prognostic accuracy for tuberculosis progression has recently been created. The rate-limiting host enzyme for the conversion of tryptophan to kynurenine, indoleamine 2,3-dioxygenase (IDO), is greatly elevated in the lungs of tuberculosis disease patients. Targeted study on tryptophan in tuberculosis disease indicates that such decreases may also resembled this upregulation. Although tuberculosis diagnosis has improved with the use of interferon release assay and tuberculosis nucleic acid amplification, tuberculosis control is made difficult by the lack of a biomarker to diagnose active tuberculosis disease. We hope that the reader of this work can develop an understanding of the advantages of metabolomics testing, particularly as a sort of testing that can be used for both diagnosing and monitoring a patient's response to treatment for tuberculosis.

Diagnostic Performance of Anti-Topoisomerase-I, Anti-Th/To Antibody and Anti-Fibrillarin Using Immunoblot Method in Systemic Sclerosis Related Interstitial Lung Disease Patients.

Purpose: Systemic Sclerosis related Interstitial Lung Disease (SSc-ILD) is the most common clinical manifestation of SSc with a high morbidity and mortality rate. However, the Thorax High-Resolution Computed Tomography (HCRT) as the gold standard diagnostic tool for SSc-ILD is not widely equipped in health-care facilities. Recently, specific autoantibody examination (anti-topoisomerase-1 (ATA), anti-Th/To antibody, and anti-fibrillarin) has been studied and used for SSc-ILD diagnosis. This study aims to evaluate the diagnostic performance of specific autoantibody examination among SSc-ILD. Patients and Methods: This retrospective study reviews data from local dedicated SSc database (Sclerosis Systemic Register System Development Electronic Medical Record) which were collected between March 2019 and August 2021. Population of this study include adult inpatients and outpatients at Dr. Hasan Sadikin General Hospital, who have been diagnosed with SSc based on ACR/EULAR 2013 criteria, which met inclusion and exclusion criteria. The SSc patients were grouped into SSc-ILD and SSc non-ILD based on HRCT and tested for SSC-ILD specific autoantibody test (ATA, anti-Th/To antibody, and anti-fibrillarin) to obtain the diagnostic performance (sensitivity, specificity, and positive- and negative-predictive value). Results: A total of 74 subject grouped into 47 SSc-ILD and 27 SSc-non ILD patients. ATA validity test results showed 85.1% sensitivity, 19.2% specificity, 65.6% PPV, and 41.7% NPV. Anti-Th/To antibody obtained 27.7% sensitivity, 88.9% specificity, 81.3% PPV, and 41.4% NPV. The anti-fibrillarin validity test result showed a 12.8% sensitivity, 96.3% specificity, 85.7% PPV, and 38.8% NPV. The combination of the three parameters had 95.7% sensitivity, 18.5% specificity, 67.1% PPV, and 71.4% NPV. Conclusion: The combination of the SSc-ILD specific autoantibody test and HCRT is expected to detect all affected patients. Based on these results, SSc-ILD autoantibody-specific test can be used as an alternative examination for screening and diagnosis in health-care facilities that are not equipped with HRCT.

Lumbar interlaminar epidural steroid injections for chronic low back- and lower extremity-pain in Sjogren's syndrome: A case report.

INTRODUCTION AND IMPORTANCE: Peripheral nervous system involvement is very common in Sjogren's syndrome (SS); however, polyradiculopathy has been reported rarely in association with SS, and predominantly chronic forms have been described. Here, we reported a case from our Neurosurgery Department in Intan Medika KIM Hospital, Bangka Island, Pangkalpinang, Indonesia; as Academic Health System of Universitas Padjadjaran. CASE PRESENTATION: A 32-year-old woman, diagnosed with Sjogren's syndrome that was characterized by anti-nuclear, anti-Ro, anti-La and anti dsDNA-antibodies positives since 3 years ago; consulted to our department for a chronic low back with a radicular pain in both lower limbs from the gluteal area to both feet together with numbness, hyperstesis and allodynia. The pain was evaluated by the visual analogue scale (VAS) score of 8; we then performed cervico-lumbal computed tomography (CT) scan that demonstrated multiple protruded discs of the cervical- and lumbar-spine. CLINICAL DISCUSSION: Pain was treated with lumbar interlaminar epidural steroid injections as a safe technique that allows relieving patient symptoms; after 10 min, the patient experienced an improvement in her pain with reduced scores to 0-1 in VAS, as well as a significant improvement on her quality of life later on. CONCLUSION: The use of lumbar interlaminar epidural steroid injections for an alternative therapeutic for neuropathic pain in SS gives a satisfactory result in terms of improvement of pain as well as a significant improvement on patients' quality of life.