Muscle strength, not muscle mass, determines the health-related quality of life in Indonesian women with systemic lupus erythematosus.

OBJECTIVE: No study evaluated the impact of low muscle strength and mass on the Sarcopenia-related Quality of Life (SarQoL) in women with SLE. METHODS: This cross-sectional study recruited 145 women with SLE consecutively; muscle strength was measured with a calibrated Jamar handheld dynamometer, muscle mass was measured with appendicular muscle mass index (Tanita MC-780 MAP body impedance analyser) and health-related quality of life with SarQoL Questionnaire. The cut-off points for low muscle strength, low muscle mass and sarcopenia were derived from the Asian Working Group on Sarcopenia 2019. Statistical analysis was conducted with a t-test for mean difference, and logistic regression was used to evaluate for low muscle strength contributing factors. RESULTS: There was a significant difference in the mean total score of SarQoL in individuals with normal compared with low muscle strength (74.36 vs 64.85; mean difference 9.50; 95% CI 2.10 to 5.33; p<0.001). On the other hand, there was no difference in individuals with normal compared with low muscle mass (71.07 vs 70.79; mean difference 0.28; -5.18 to 5.74; p=0.91). After minimally adjusted with age, we found moderate-severe joint pain (B -9.280; p<0.001) and low muscle strength (B -6.979; p=0.001) to be independently associated with low mean SarQoL total score. CONCLUSION: There was a lower total SarQoL score in individuals with low muscle strength but not with low muscle mass.

Immunological dysfunction and mast cell activation syndrome in long COVID.

At least 65 million people around the world suffer from long COVID-19, with the majority of cases occurring in the productive age (36-50 years old). Individuals with long COVID-19 are confounded with multiple organ system dysfunctions, long-term organ injury sequelae, and a decreased quality of life. There is an overlapping of risk factors between long COVID-19 and other postviral infection syndromes, so advances in research could also benefit other groups of patients. Long COVID-19 is the consequence of multiple immune system dysregulation, such as T-cell depletion, innate immune cell hyperactivity, lack of naive T and B cells, and elevated signature of pro-inflammatory cytokines, together with persistent severe acute respiratory syndrome-coronavirus 2 reservoir and other consequences of acute infection. There is an activated condition of mast cells in long COVID-19, with abnormal granulation and excessive inflammatory cytokine release. A study by Weinstock et al. indicates that patients with long COVID-19 suffer the same clinical syndrome as patients with mast cell activation syndrome (MCAS). Diagnosis and treatment of MCAS in patients with long COVID-19 will provide further symptomatic relief, and manage mast cell-mediated hyperinflammation states, which could be useful in the long-term control and recovery of such patients.

Risk of adverse events following CoronaVac's COVID-19 vaccination in women with and without autoimmunity.

Introduction: Adverse Events Following Immunization (AEFI) of the COVID-19 vaccine is one of the important considerations, especially in patients with autoimmunity. This study aims to compare the number of CoronaVac AEFIs in women with and without autoimmunity. Methodology: This is a retrospective cohort study with an unpaired comparative analytic design with a retrospective cohort method. We recruited 602 volunteers, 182 women with autoimmunity and 420 without autoimmunity. We included women who received the CoronaVac vaccine, aged 17-65 years. Data were analyzed using the chi-square or fisher exact method as an alternative. Results: We found a generally increased risk for AEFI in women with autoimmunity (RR = 1.179; 95% CI 1.059-1.313; p = 0.007) compared to women without autoimmunity, especially for systemic (RR = 1.1271; 95% CI 1.045-1.545; p = 0.025), allergic (RR = 2.052; 95% CI 1.070-3.932; p = 0.045), fever (RR = 2.163 95%; CI 1.093-4.282; p = 0.039), fatigue (RR = 2.182 95%; CI 1.558-3.056; p = 0.001), and headache (RR = 1.619 95%; CI 1.164-2.251; p = 0.006). On the other hand, we found no increased risk for the overall severity of AEFI (RR = 0.851 95% CI; 0.655-1.105; p = 0.256). We also found a relapse of autoimmune condition in 10.4% (n = 19) after CoronaVac vaccination. Conclusions: There is an increased risk of AEFI after CoronaVac vaccination in women with autoimmunity compared to those without the condition. Although the severity of AEFIs and risk of autoimmune relapse were relatively low.

Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs.

Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.

The impact of low muscle function on health-related quality of life in Indonesian women with systemic lupus erythematosus.

OBJECTIVE: There was no study aimed at evaluating the effect of muscle function on SLE patients' quality of life using the Sarcopenia Quality of Life (SarQoL) questionnaire. METHODS: This cross-sectional study recruited 61 women with SLE consecutively, muscle function was measured with Jamar handheld-dynamometer and 6-meter walk test, HRQoL was measured with Sarcopenia Quality of Life (SarQoL) questionnaire. The cut-off point for low muscle strength (<18 kg) and low gait speed (<1.0 m/s) was according to the Asian Working Group on Sarcopenia 2019 criteria. Statistical analysis was conducted with a t-test for mean difference, and linear regression was used to adjust confounders (age, protein intake, physical exercise, and disease activity). RESULTS: The subjects' mean muscle strength was 19.54 kg (6.94), and 44.3% (n = 27) was found to have low muscle strength. The subjects' mean gait speed was 0.77 m/s (0.20), and 90.3% (n = 55) was found to have low gait speed. The difference of total SarQoL score in subjects with normal and low muscle strength was found to be significant; 74.86 (9.48) vs. 65.49 (15.51) (p = 0.009), and still statistically significant after adjustments with age, protein intake, physical exercise level, and disease activity [B 0.56; 95% CI 0.08-1.03; p = 0.022]. The difference of total SarQoL score in subjects with normal and low physical performance was found to be not significant, 70.67 (11.08) vs. 70.72 (13.56) (p = 0.993). CONCLUSION: There was a significant difference in SarQoL's total score in normal compared with low muscle strength groups of Indonesian women with SLE.

Metformin improves FOXP3 mRNA expression through suppression of interferon gamma levels in pristane-induced murine models of lupus.

Background:  A recent study has indicated the potential of metformin therapy for lupus in animal models, but there has been no study evaluating the effect on pristane-induced lupus. This study aims to evaluate the effect of intraperitoneal versus oral metformin on interferon (IFN)-γ levels and FOXP3 mRNA expression on pristane-induced female BALB/c mice. Methods: In total, 31 female BALB/c mice, aged 6 weeks, were intraperitoneally induced with 0.5 ml of pristane (2,6,10,14-tetramethylpentadecane). After 120 days, the mice were grouped and treated with various treatments: normal saline 100 mcl, oral metformin 100mg/kgBW, or intraperitoneal metformin 100mg/kgBW. After 60 days of treatment, all treatment groups were sacrificed, and kidney specimens prepared and stained using hematoxylin and esosin. Results: IFNγ levels of saline controls vs. oral metformin group was 309.39 vs. 292.83 pg/mL (mean difference 16.56 pg/mL; 95% CI 0.74-32.37; p=0.042), and saline control vs. intraperitoneal metformin group was 309.39 vs. 266.90 pg/mL (mean difference 42.49 pg/mL; 95% CI 29.24-55.73 pg/mL; p<0.004). FOXP3 mRNA expression changes in saline controls vs. oral metformin group was 6.90 vs. 7.79-fold change (mean difference -0.89-fold change; 95% CI -1.68-(-0.11); p=0.03)  and in saline controls vs. intraperitoneal metformin group was 6.90 vs. 9.02-fold change (mean difference -2.12-fold change; 95% CI -2.99-(-1.25); p=<0.001). Correlation analysis of FOXP3 mRNA expression and IFNγ level changes revealed a Pearson correlation of -0.785 (p=0.001) and R2 value of 0.616 (p=0.001). Conclusion: Metformin is a potential new therapy to reduce the levels of IFNγ and increase FOXP3 mRNA expression in mice models of systemic lupus erythematosus. Intraperitoneal metformin, i.e intravenous administration in human, could provide a novel route of administration to improve the effect of metformin for lupus patients.

Relationship between metformin and frailty syndrome in elderly people with type 2 diabetes.

AIM: to explore the possibility of metformin protective effect on frailty syndrome. METHODS: this was a case control study conducted in subjects' ≥60 years old who visited the Geriatrics and Diabetes outpatient clinic of Cipto Mangunkusumo National Referral Hospital between March and June 2013. Diagnosis of frailty was established using the FI-40 item criteria. Statistical analysis was done with chi-square method for bivariate and logistic regression method in multivariate analysis, all data was accompanied with 95% confidence interval. RESULTS: frailty syndrome was found in 25% of subjects (n = 59), with median age of 72 years old (SD 6.27) and median of FI-40 item score was 0.18 (SD 0.085). Metformin was found to have a significant relationship with frailty syndrome in the elderly diabetics, which retained significant value after multivariate analysis (adjusted OR 0.043; 95% CI 0.019-0.099; p < 0.001). CONCLUSION: metformin was shown to have protective effect against frailty syndrome in elderly diabetics.

Clinical manifestations and antiretroviral management of HIV/AIDS patients with tuberculosis co-infection in Kramat 128 Hospital.

AIM: to give a description of HIV-AIDS and tuberculosis co-infection in Jakarta, viewed from the perspective of virologic and immunologic status and the correct selection of antiretrovirals. METHODS: cross-sectional descriptive study was performed on the outpatient clinic of Kramat 128, from June to July 2007. Tuberculosis infection was confirmed chest X-ray or sputum acid fast smear. Viral load was determined by Polymerase Chain Reaction (PCR) and CD4 count done by flow cytometry. The data were then analyzed using SPSS 14th and Chi Square tests for proportional data. RESULTS: the study enrolled 130 patients with the prevalence of tuberculosis co-infection of 66.9% (n=87). The TB co-infected patients came with more clinical manifestations (3-4 manifestations) than the non co-infected ones (2-3 manifestations; p<0.001). They also underwent more hospitalizations (44.8% vs. 11.6%, p=0.003), had lower CD4 levels (126.49 cell/microL vs. 240.68 cell/microL; p=0.001) and more patients with CD4 levels of below 100 cell/microL (64.6% vs. 25.6%; p<0.001). The co-infected patients had more virologic failure than the non co-infected ones (38% vs. 12.5%; p=0.030), and so did the co-infected patients treated with nevirapine than those treated with efavirenz (37.8% vs. 6.3%; p=0.019). CONCLUSION: tuberculosis co-infection complicated the clinical management of People Living with HIV-AIDS (PLWHA) and the antiretroviral regimen selection in these patients need to be modified. Subsequent studies were needed to confirm this study result of superior efavirenz based therapy in the TB co-infected PLWHA.