194 results on '"Chi Chiu Mok"'
Search Results
2. Disease Activity Indices in Systemic Lupus Erythematosus: What Is New?
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Fung Lam and Chi Chiu Mok
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Lupus ,Disease Activity ,Composite ,Index ,Assessment ,Tool ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Systemic lupus erythematosus (SLE) is a complicated multisystem autoimmune disease that carries substantial mortality and morbidity. The development of new therapies is partly hindered by the lack of a flawless instrument to gauge disease activity in different organs for the primary efficacy outcome. Until a global consensus is reached regarding the most preferred assessment tool, application of any of the existing disease activity indices is acceptable in clinical practice and research. However, one should have a more thorough understanding of the strength and limitations of individual disease activity instruments. This article updates the SLE disease activity indices commonly used in clinical trials and their latest stage of development.
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- 2023
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3. Multisystem Inflammatory Syndrome in a Patient with SLE
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Chris Ching Lam Cheung, Kelly Kar Li Chan, Chiu Sum Chu, and Chi Chiu Mok
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COVID-19 ,SARS-CoV-2 ,Autoimmune ,Lupus ,Complications ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Coronavirus disease 2019 (COVID-19) was one of the most important infections in the past few years. Although most cases of COVID-19 are mild, serious complications may arise. The multisystem inflammatory syndrome (MIS) is a rare but severe, yet poorly understood complication of COVID-19. It was first described in childhood patients with COVID-19 (MIS-C) but is increasingly reported in adults. MIS-A may lead to diagnostic and therapeutic dilemma as its manifestations may mimic a flare of the underlying disease and the use of immunosuppressive therapy may further increase the risk of other infective complications in these patients. However, MIS-A has rarely been reported in patients with pre-existing autoimmune conditions. We hereby present a patient with systemic lupus erythematosus who developed severe MIS-A 6 weeks after a recent SARS-CoV-2 infection.
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- 2023
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4. The Potential Use of Arsenic Trioxide in the Treatment of Systemic Lupus Erythematosus
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Tsz Ching Mok and Chi Chiu Mok
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arsenic trioxide ,non-leukemic ,autoimmune ,immune-mediated ,rheumatic ,lupus ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Arsenic trioxide (ATO) is now part of the standard regimen for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. The availability of an oral form of ATO has greatly reduced the incidence of cardiotoxicity as compared to intravenous (IV) administration. Increasing evidence suggests that ATO has anti-inflammatory properties that may be useful for the treatment of autoimmune diseases. These include the modulation of Treg cell activation, Th1/Th2 and Th17/Treg balance, depletion of activated T cells and plasmacytoid dendritic cells, and influence of B-cell differentiation, leading to reduced autoantibody and cytokine production. ATO has also been shown to induce apoptosis of activated fibroblast-like synoviocytes through the generation of reactive oxygen species and alter the gut microbiota in collagen-induced arthritis. Despite the emergence of newer treatment modalities, the treatment of systemic lupus erythematosus (SLE), especially refractory manifestations, remains a challenge, owing to the paucity of effective biological and targeted therapies that are devoid of adverse effects. Oral ATO is an attractive option for the treatment of SLE because of the lower cost of production, convenience of administration, and reduced cardiotoxicity. This article summarizes the anti-inflammatory mechanisms of ATO and its potential application in the treatment of SLE and other rheumatic diseases.
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- 2024
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5. Anti-CD20 Therapy for Lupus Nephritis: A Blind Alley or Broad Avenue?
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Chi Chiu Mok
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2023
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6. Prediction of a Positive ANA Result for a Rheumatological Diagnosis in an Outpatient Setting
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Chiu Sum Chu, Ling Yin Ho, and Chi Chiu Mok
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ANA ,Prediction ,Rheumatic ,Autoimmune ,Diagnosis ,Referral ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective: To study the predictive value of a positive anti-nuclear antibody (ANA) for a rheumatological diagnosis in an outpatient setting. Methods: Individuals who were referred to the rheumatology outpatient clinics because of a positive ANA between July 2014 and June 2015 were retrospectively reviewed. Presenting symptoms in addition to a positive ANA and whether a final rheumatological diagnosis was made were recorded. The positive predictive value of a positive ANA and its titer for a rheumatological diagnosis, with and without accompanying symptoms was evaluated. Results: A total of 230 patients were included (82% women, age 47.7 ± 14.1 years [range 18-84]). Family medicine and the general outpatient clinic were the main sources of referral (32.2%), followed by ophthalmology (13.0%) and otorhinolaryngology (11.7%). A final rheumatological diagnosis was made in 54 (23.5%) patients, with rheumatoid arthritis being the commonest diagnosis (40.7%). In the absence of any associated symptoms, the predictive value of a positive ANA was 0%. The presence of Raynaud’s phenomenon (100%), joint swelling (59.5%), and joint stiffness (48.9%) predicted a better final rheumatological diagnosis along with a positive ANA. ANA titers of 1:80 or less had a low sensitivity for rheumatic diseases. A receiver operating characteristic (ROC) curve analysis showed that an ANA titer of [Formula: see text]1:128 best predicted a rheumatological diagnosis (AUC 0.78 [0.71–0.85]; sensitivity 0.78; specificity 0.64). Conclusions: To improve the prediction for a rheumatological diagnosis, referral for a positive ANA test should be more appropriately done with compatible symptoms.
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- 2023
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7. The Performance of the Hospital Anxiety and Depression Scale for Screening of Anxiety and Depressive Disorders in Chinese Patients with Rheumatoid Arthritis in Hong Kong
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Eugenia Yung Ching Lok and Chi Chiu Mok
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Psychiatric Disorder ,Depression ,Anxiety ,Hospital Anxiety and Depression Scale ,Rheumatoid Arthritis ,Screening ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective: To evaluate the performance of the Hospital Anxiety and Depression Scale (HADS) for screening of depressive disorders and anxiety disorders in patients with rheumatoid arthritis (RA) in Hong Kong. Methods: Consecutive RA patients in the outpatient clinic of Pok Oi Hospital were invited to complete the validated Chinese-Cantonese version of the HADS questionnaire before clinical assessment by a psychiatrist for depressive disorders and anxiety disorders using the Chinese-bilingual Structured Clinical Interview for DSM-IV Axis I disorders, patient research version. Psychometric properties of the HADS were analyzed by the receiver operating characteristic (ROC) curve analysis. Results: For the HADS full scale, sensitivity and specificity at the optimal cut-off score of 16 for any psychiatric disorders were 83.0% and 81.0%, respectively (area under ROC curve [AUC] 0.91). For the depression subscale (HADS-D), sensitivity and specificity at the optimal cut-off score of 10 for any depressive disorders were 89.7% and 84.8%, respectively (AUC 0.93). For the anxiety subscale (HADS-A), sensitivity and specificity at the optimal cut-off score of 8 for any anxiety disorders were 88.5% and 74.1%, respectively (AUC 0.87). The HADS-D showed better screening properties for any depressive disorders than major depressive disorder. The HADS-A showed better screening properties for generalized anxiety disorder than any anxiety disorders. Conclusion: The HADS had good performance to screen for any psychiatric disorders and the HADS-D had good performance to screen for any depressive disorders. On the other hand, the HADS-A performed better for generalized anxiety disorder than for any anxiety disorders.
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- 2022
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8. Risk and Factors associated with disease manifestations in systemic lupus erythematosus – lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients
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Shirley C. W. Chan, Yong-Fei Wang, Desmond Y. H. Yap, Tak Mao Chan, Yu Lung Lau, Pamela P. W. Lee, Wai Ming Lai, Shirley K. Y. Ying, Niko K. C. Tse, Alexander M. H. Leung, Chi Chiu Mok, Ka Lai Lee, Teresa W. L. Li, Helen H. L. Tsang, Winnie W. Y. Yeung, Carmen T. K. Ho, Raymond W. S. Wong, Wanling Yang, Chak Sing Lau, and Philip H. Li
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systemic lupus erythematosus ,lupus nephritis ,risk assessment ,prediction ,model ,Immunologic diseases. Allergy ,RC581-607 - Abstract
ObjectivesLupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients – Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus – Lupus Nephritis (RIFLE-LN).MethodsDemographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated.ResultsA total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70).ConclusionBy using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.
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- 2023
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9. Symposium 6 Biological Therapies for Systemic Lupus Erythematosus: Something Old, Something New
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Chi Chiu MOK
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Immunologic diseases. Allergy ,RC581-607 - Abstract
The ultimate goal of treatment of systemic lupus erythematosus (SLE) is to prolong survival without compromising the quality of life. The survival rates of SLE have plateaued since the 2000s’ and morbidities related to disease activity and treatment are still problematic. A big unmet need for SLE therapy is to develop strategies that can enhance efficacy, reduce disease flares and drug related complications. Cocktail immunosuppressive therapies for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, risk of infective complications, adoption of a step-up or step-down approach and the choice of agents are still controversial, partly because of the issue of cost-effectiveness. Belimumab is the first biological agent licensed for pediatric and adult patients with renal and non-renal SLE, based on several pivotal randomized controlled trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, BLISS-LN). The continuous use of belimumab enables reduction of disease flares, glucocorticoid doses and organ damage. Anifrolumab, a monoclonal antibody against type I interferon receptors, has shown efficacy for non-renal SLE in the TULIP studies. It is recently licensed for moderate to severe SLE patients who are receiving standard therapies. Although rituximab did not show benefit in renal and non-renal SLE, it is commonly used off-label to treat refractory lupus manifestations. The newer generation anti-CD20 biologic, obinutuzumab, shows promising preliminary results in a phase 2 lupus nephritis (LN) trial. Combination of anti-CD20 and anti-BAFF is being studied in LN but the results are conflicting hitherto. Ianalumab, a monoclonal antibody against BAFF receptor that exhibits dual mechanisms of action (BAFF inhibition and B cell depletion), is being studied in LN. The updated 2023 EULAR recommendations for SLE have included the role of biological agents in the treatment algorithm. Belimumab and anifrolumab may be considered in non-major organ SLE, including skin disease, that is refractory to hydroxychloroquine with or without other immunosuppressive agents. Initial combination therapy of glucocorticoids, mycophenolate mofetil or low dose cyclophosphamide, with belimumab is an option for the treatment of severe LN, and belimumab may be used as long-term maintenance therapy of SLE/LN. In this talk, the evidence and the role of the older and newer biologic and targeted agents in SLE/LN will be reviewed.
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- 2023
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10. Osteoporosis in Rheumatic Diseases
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Chi Chiu Mok
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Rheumatic ,Autoimmune ,Bone Remodeling ,Osteoporosis ,Fracture ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The risk of osteoporosis and fragility fracture is increased in patients with autoimmune rheumatic diseases. Although the use of glucocorticoids is the major contributing factor, inflammation mediated by cytokines and growth factors and other medications, including the biologic and targeted disease-modifying antirheumatic drugs, also play important roles in bone remodeling. Pro-inflammatory cytokines such as IL-1, IL-6, IL-17, and TNF[Formula: see text] increase RANK expression and promote osteoclast activity while inhibiting osteoblast-mediated bone formation through the Dickkopf-1 pathway. Certain autoantibodies stimulate differentiation of the osteoclasts, resulting in localized bone resorption. This article covers the prevalence and risk factors for osteoporosis in patients with common rheumatic diseases and the role of inflammatory cytokines and other clinical factors. Controlling disease-related inflammation and optimizing the diagnostic and therapeutic instrumentation is needed to reduce fragility fractures in patients with rheumatic diseases.
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- 2022
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11. Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis
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Samar A. Soliman, Samantha Stanley, Kamala Vanarsa, Faten Ismail, Chi Chiu Mok, and Chandra Mohan
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biomarker ,lupus nephritis ,fractional excretion ,ALCAM ,platelet factor-4 ,properdin ,Immunologic diseases. Allergy ,RC581-607 - Abstract
ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.
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- 2022
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12. The Hong Kong Society of Rheumatology Consensus Recommendations for COVID-19 Vaccination in Adult Patients with Autoimmune Rheumatic Diseases
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Ho So, Chi Chiu Mok, and Ronald Man Lung Yip
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covid-19 ,vaccine ,vaccination ,rheumatic ,rheumatology ,autoimmune ,recommendations ,consensus ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Patients with autoimmune rheumatic diseases are potentially at risk of more serious Coronavirus Disease 2019 (COVID-19) infection and increased mortality due to immunosuppressive therapies and disease-related medical comorbidities. Uncertainty about the safety and efficacy of the COVID-19 vaccines is a major deterrent for patients to participate in the vaccination program. The Hong Kong Society of Rheumatology took the lead to publish a set of consensus statements for COVID-19 vaccination in adult patients with autoimmune rheumatic diseases through a Delphi exercise that involved the senior members of the Society. This serves as a guide to rheumatologists and other specialists, nurses, healthcare professionals, and public regarding COVID-19 vaccination in autoimmune rheumatic diseases.
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- 2021
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13. A Consensus for the Management of Systemic Lupus Erythematosus in Asia
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Chi Chiu Mok
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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14. Validation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in ANA-positive Chinese patients
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Yuen Kwan Chung, Ling Yin Ho, Carolyn Lee, Chi Hung To, and Chi Chiu Mok
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Background: The aim of this study was to validate the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for systemic lupus erythematosus (SLE) in antinuclear antibody (ANA)-positive Chinese patients. Methods: Medical records of all adult patients who attended the rheumatology out-patient clinics between May and September 2019 were reviewed. Patients with ever ANA positive (titre ⩾1:80) were included and evaluated for the fulfilment of the 2019 EULAR/ACR, 2012 Systemic Lupus International Collaborating Clinics (SLICC) and 1997 ACR criteria for SLE classification. The performance of these criteria in predicting a clinical diagnosis of SLE as judged by an independent panel of rheumatologists was studied and compared in different subgroups. Results: A total of 1533 patients (88.2% women; age at first clinic attendance 45.5 ± 15.6 years) were studied and 562 patients were judged to be clinical SLE. The sensitivity and specificity of the EULAR/ACR (⩾10 points), SLICC and ACR criteria for a clinical diagnosis of SLE was 96.1%, 97.9% and 86.1%; and 85.8%, 86.3% and 94.3%, respectively. Applying the attribution rule to the non-SLE controls, the specificity of the three criteria increased to 95.0%, 92.5% and 98.8%, respectively. The specificity of the EULAR/ACR criteria was higher in male patients (97.9%), those aged >50 years (97.0%) and disease duration of ⩽3 years (97.6%). Using a cut-off of 12 points, the specificity of the EULAR/ACR criteria was further increased (96.6%) while a high sensitivity (95.0%) was maintained. Conclusion: In Chinese patients with a positive ANA, the EULAR/ACR criteria for clinical SLE perform equally well to the SLICC criteria. Both the EULAR/ACR and SLICC are more sensitive but less specific than the ACR criteria. The specificity of all the three criteria is enhanced by applying the attribution rule to controls. The specificity of the EULAR/ACR criteria is higher in certain patient subgroups or when the cut-off score is raised.
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- 2022
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15. Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups
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Yong-Fei Wang, Yan Zhang, Zhiming Lin, Huoru Zhang, Ting-You Wang, Yujie Cao, David L. Morris, Yujun Sheng, Xianyong Yin, Shi-Long Zhong, Xiaoqiong Gu, Yao Lei, Jing He, Qi Wu, Jiangshan Jane Shen, Jing Yang, Tai-Hing Lam, Jia-Huang Lin, Zhi-Ming Mai, Mengbiao Guo, Yuanjia Tang, Yanhui Chen, Qin Song, Bo Ban, Chi Chiu Mok, Yong Cui, Liangjing Lu, Nan Shen, Pak C. Sham, Chak Sing Lau, David K. Smith, Timothy J. Vyse, Xuejun Zhang, Yu Lung Lau, and Wanling Yang
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Science - Abstract
The presentation of systemic lupus erythematosus has been known to differ by ancestry, but the underlying genetic factors remain unclear. Here, the authors report ancestry-specific susceptibility loci and better risk prediction when using data from matched ancestral groups.
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- 2021
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16. Therapeutic Plasma Exchange in Patients with Systemic Lupus Erythematosus
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Cheuk Man Ho and Chi Chiu Mok
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plasma exchange ,lupus ,complications ,refractory ,therapeutics ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease with involvement of multiple systems. Despite the therapeutic advances in the past few decades, refractory SLE causing organ damage and life-threatening complications still poses a therapeutic challenge. Therapeutic plasma exchange is considered as one of the rescue therapies used in refractory SLE. However, the level of evidence supporting its use is low. This article reviews the current evidence of the application of plasmapheresis in the treatment of SLE.
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- 2020
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17. Glucocorticoid-Induced Osteoporosis: The Potential Role of Romosozumab
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Jacqueline So and Chi Chiu Mok
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glucocorticoid-induced osteoporosis ,romosozumab ,denosumab ,teriparatide ,corticosteroid ,fracture ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Glucocorticoid (GC)-induced osteoporosis (GIOP) is a major problem in patients with rheumatic diseases. The deleterious effect of GC on bone turnover is rapid and dose-dependent, with a predilection on the trabecular bone, resulting in vertebral fractures. Early recognition and prompt treatment of GIOP helps prevent bone loss and reduce fractures. There are pitfalls in current assessment tools for GIOP by dual-energy X-ray absorptiometry (DXA) and fracture risk assessment tool (FRAX) estimation formula. In this review, we evaluate different assessment methods for GIOP and summarize current therapies of GIOP, including the antiresorptive and anabolic agents. The potential role of newer anti-osteoporosis agent romosozumab, an anti-sclerostin monoclonal antibody, is also discussed.
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- 2020
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18. Glucocorticoid Withdrawal in Lupus Nephritis: A Study Protocol and Literature Review
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Natalia Chu Oi Ciang and Chi Chiu Mok
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lupus ,glucocorticoids ,steroid ,flare ,nephritis ,withdrawal ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Although glucocorticoids (GCs) are the cornerstone for the treatment for systemic lupus erythematosus (SLE), they are associated with a number of adverse effects. Recently, an open randomized controlled trial (RCT) conducted in France showed that flares of SLE in 12 months were significantly more common with GCs withdrawal than continuation in stable patients. However, the study did not separately report results on subsets of SLE patients with organ threatening disease such as lupus nephritis (LN). We hereby present a literature review on GCs withdrawal in SLE and propose a protocol for a multicenter RCT in Hong Kong to evaluate the feasibility of withdrawal of low-dose GCs in stable LN patients who are in clinical remission.
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- 2020
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19. Estimation of fracture risk by the FRAX tool in patients with systemic lupus erythematosus: a 10-year longitudinal validation study
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Chi Chiu Mok, Sau Mei Tse, Kar Li Chan, and Ling Yin Ho
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Background: The fracture risk assessment tool has been widely used to stratify the 10-year fracture risk to guide therapy. Using the actual fracture data of a 10-year longitudinal cohort of older patients with systemic lupus erythematosus, we reported an underestimation of the tool in predicting major symptomatic osteoporotic fractures. Treatment of osteoporosis in systemic lupus erythematosus should not be based on fracture risk estimation alone. Relevant time-dependent risk factors should be taken into account for an individualized decision. Objective: To compare the observed fracture incidence in a 10-year longitudinal cohort of patients with systemic lupus erythematosus (SLE) with the fracture risk prediction from the fracture risk assessment (FRAX) tool. Methods: Adult patients (⩾40 years) with SLE who had a first DEXA scan performed in 2005–2009 were studied. The 10-year rates of major osteoporotic and hip fractures were estimated by FRAX using clinical data at DEXA with adjustment for prednisolone dosage. The actual incidence of clinical fractures at 10 years was compared with the estimated rates. Factors associated with new fractures were studied by logistic regression. Results: A total of 229 SLE patients were studied (age: 50.2 ± 6.6 years, 93% women). Glucocorticoid was used in 148 (65%) patients at baseline (mean dose: 7.3 ± 6.9 mg/day; 34% ⩾ 7.5 mg/day). Osteoporosis (bone mineral density T score ⩽ –2.5) at the hip, femoral neck, or spine was present in 61 (27%) patients. The estimated 10-year risk of major osteoporotic and hip fractures by FRAX was 3.4 ± 4.5% and 0.95 ± 2.3%, respectively. After 10 years, three patients developed hip fracture, 6 patients had limb fractures and 20 patients had symptomatic vertebral fractures (major osteoporotic fracture 12.7%, hip fracture 1.3%). The actual major osteoporotic fracture rate was significantly higher than the FRAX estimation (12.7% vs 3.4%; p
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- 2022
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20. COVID-19 and Rheumatic Diseases: Practical Issues
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Ho So and Chi Chiu Mok
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covid-19 ,sars-cov-2 ,rheumatic diseases ,Immunologic diseases. Allergy ,RC581-607 - Abstract
On March 12, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic. The rapidly increasing number of cases and deaths have overwhelmed the health care system worldwide. We aimed to provide a narrative review on some practical issues of COVID-19 and rheumatic diseases with the limited data to the date of April 26, 2020.
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- 2020
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21. Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities
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Samantha Stanley, Kamala Vanarsa, Samar Soliman, Deena Habazi, Claudia Pedroza, Gabriel Gidley, Ting Zhang, Shree Mohan, Evan Der, Hemant Suryawanshi, Thomas Tuschl, Jill Buyon, Chaim Putterman, Chi Chiu Mok, Michelle Petri, Ramesh Saxena, and Chandra Mohan
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Science - Abstract
Developing noninvasive diagnostic biomarkers for lupus nephritis (LN) diagnosis is an important clinical goal. Here the authors identify urinary proteins correlated with active LN and disease severity, which differ across ethnicities but collectively outperform the current clinical method.
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- 2020
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22. Management of glucocorticoid-related osteoporotic vertebral fracture
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Stella Pui Yan Wong and Chi Chiu Mok
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
The vertebral column is the most common site of osteoporotic fractures in long-term users of glucocorticoids. Vertebral fracture leads to significant morbidities such as unrelenting pain, spinal deformities and reduced mobility, leading to diminished quality of life. Epidemiological data on the prevalence of glucocorticoid-induced vertebral fractures are limited. As vertebral fracture is a strong risk factor for further fragility fractures and mortality, it should be treated appropriately. This article reviews recent data on the prevalence of vertebral fractures in glucocorticoid users, fracture risk stratification, and evidence-based treatment options. The risk of osteoporotic fractures estimated by FRAX should be adjusted for glucocorticoid users. The first-line treatment of glucocorticoid-induced osteoporosis remains the bisphosphonates. Teriparatide and denosumab are alternative options. Percutaneous vertebroplasty and kyphoplasty may be considered for symptomatic control of acute vertebral fracture-related pain when conservative measures fail. Keywords: Glucocorticoids, Vertebral fracture, Fragility, Osteoporosis
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- 2020
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23. The CD6/ALCAM pathway promotes lupus nephritis via T cell–mediated responses
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Samantha A. Chalmers, Rajalakshmy Ayilam Ramachandran, Sayra J. Garcia, Evan Der, Leal Herlitz, Jeanette Ampudia, Dalena Chu, Nicole Jordan, Ting Zhang, Ioannis Parodis, Iva Gunnarsson, Huihua Ding, Nan Shen, Michelle Petri, Chi Chiu Mok, Ramesh Saxena, Krishna R. Polu, Stephen Connelly, Cherie T. Ng, Chandra Mohan, and Chaim Putterman
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Autoimmunity ,Medicine - Abstract
T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6+ and ALCAM+ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target.
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- 2022
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24. The 2019 Updated Hong Kong Society of Rheumatology Consensus Statements for the Management of Rheumatoid Arthritis
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Chi Chiu Mok
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2019
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25. Update on Symptomatic Treatment of Acute Vertebral Compression Fracture
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Stella Pui Yan Wong and Chi Chiu Mok
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vertebral ,fracture ,osteoporosis ,vertebroplasty ,kyphoplasty ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The vertebral column is the most common site of osteoporotic fracture in older individuals and in those using long-term glucocorticoids. Vertebral compression fracture leads to significant morbidities such as acute and chronic pain, spinal deformities and neurological complications, resulting in reduced mobility and quality of life. As a previous vertebral compression fracture is a strong risk factor for further fragility fractures and mortality, it should be treated appropriately. This article reviews the management of osteoporotic vertebral compression fracture and provides evidence-based treatment options.
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- 2019
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26. Cyclophosphamide Versus Obinutuzumab for the Treatment of Anti-MDA5 Positive Inflammatory Myopathy with Interstitial Lung Disease: A Study Protocol and Literature Review
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Ho So and Chi Chiu Mok
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mda5 ,inflammatory myopathy ,interstitial ,anti-cd20 ,biologics ,Immunologic diseases. Allergy ,RC581-607 - Abstract
In patients with idiopathic inflammatory myopathy, the presence of the melanoma differentiation-associated gene 5 (MDA5) antibody carries an extremely poor prognosis as a result of the associated interstitial lung disease (ILD) that is often rapidly progressive and refractory to therapies. Management of anti-MDA5 associated ILD is a challenging task as there is a paucity of clinical data and treatment guidelines in the literature. We hereby describe a proposed protocol for a multicenter randomized controlled trial to compare the efficacy of intravenous cyclophosphamide and obinutuzumab in combination with high-dose glucocorticoids and tacrolimus in terms of mortality at six months (primary outcome). The epidemiology, pathogenesis and treatment options of anti-MDA5 associated ILD are briefly reviewed.
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- 2019
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27. Drivers of Satisfaction With Care for Patients With Lupus
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Meenakshi Jolly, Bhavika Sethi, Courtney O'Brien, Winston Sequeira, Joel A. Block, Sergio Toloza, Ana Bertoli, Ivana Blazevic, Luis M. Vilá, Ioana Moldovan, Karina D. Torralba, Elvira Cicognani, Davide Mazzoni, Sarfaraz Hasni, Berna Goker, Seminur Haznedaroglu, Josiane Bourre‐Tessier, Sandra V. Navarra, Chi Chiu Mok, Ann Clarke, Michael Weisman, and Daniel Wallace
- Subjects
Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objective Quality of life (QOL) and quality of care (QOC) in systemic lupus erythematosus (SLE) remains poor. Satisfaction with care (SC), a QOC surrogate, correlates with health behaviors and outcomes. This study aimed to determine correlates of SC in SLE. Methods A total of 1262 patients with SLE were recruited from various countries. Demographics, disease activity (modified Systemic Lupus Erythematosus Disease Activity Index for the Safety of Estrogens in Lupus Erythematosus: National Assessment trial [SELENA‐SLEDAI]), and QOL (LupusPRO version 1.7) were collected. SC was collected using LupusPRO version 1.7. Regression analyses were conducted using demographic, disease (duration, disease activity, damage, and medications), geographic (eg, China vs United States), and QOL factors as independent predictors. Results The mean (SD) age was 41.7 (13.5) years; 93% of patients were women. On the univariate analysis, age, ethnicity, current steroid use, disease activity, and QOL (social support, coping) were associated with SC. On the multivariate analysis, Asian participants had worse SC, whereas African American and Hispanic patients had better SC. Greater disease activity, better coping, and social support remained independent correlates of better SC. Compared with US patients, patients from China and Canada had worse SC on the univariate analysis. In the multivariate models, Asian ethnicity remained independently associated with worse SC, even after we adjusted for geographic background (China). No associations between African American or Hispanic ethnicity and SC were retained when geographic location (Canada) was added to the multivariate model. Canadian patients had worse SC when compared with US patients. Higher disease activity, better social support, and coping remained associated with better SC. Conclusion Greater social support, coping, and, paradoxically, SLE disease activity are associated with better SC. Social support and coping are modifiable factors that should be addressed by the provider, especially in the Asian population. Therefore, evaluation of a patient's external and internal resources using a biopsychosocial model is recommended. Higher disease activity correlated with better SC, suggesting that the latter may not be a good surrogate for QOC or health outcomes.
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- 2019
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28. Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases
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Danlei Zhou, Michael Rudnicki, Gilbert T. Chua, Simon K. Lawrance, Bi Zhou, Joanne L. Drew, Fatima Barbar-Smiley, Taylor K. Armstrong, Miranda E. Hilt, Daniel J. Birmingham, Werner Passler, Jeffrey J. Auletta, Sasigarn A. Bowden, Robert P. Hoffman, Yee Ling Wu, Wael N. Jarjour, Chi Chiu Mok, Stacy P. Ardoin, Yu Lung Lau, and Chack Yung Yu
- Subjects
Anti-NMDA receptor encephalitis ,complement C4 polymorphism ,C4B mutations ,gene copy number variation ,race-specific variations ,RCCX modules ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a deficiency of C4B protein caused by genetic mutation in addition to gene copy-number variation. Those variants and mutants were characterized, sequenced and specific techniques for detection developed. Novel findings were made in four case series. First, the amino acid sequence determinant for C4B7 was likely the R729Q variation at the anaphylatoxin-like region. Second, in healthy White subject MS630, a C-nucleotide deletion at codon-755 led to frameshift mutations in his single C4B gene, which was a private mutation. Third, in European family E94 with multiplex lupus-related mortality and low serum C4 levels, the culprit was a recurrent haplotype with HLA-A30, B18 and DR7 that segregated with two defective C4B genes and identical mutations at the donor splice site of intron-28. Fourth, in East-Asian subject E133P with anti-NMDA receptor encephalitis, the C4B gene had a mutation that changed tryptophan-660 to a stop-codon (W660x), which was present in a haplotype with HLA-DRB1*04:06 and B*15:27. The W660x mutation is recurrent among East-Asians with a frequency of 1.5% but not detectable among patients with SLE. A meticulous annotation of C4 sequences revealed clusters of variations proximal to sites for protein processing, activation and inactivation, and binding of interacting molecules.
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- 2021
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29. Rheumatology Drugs and COVID-19
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Chi Chiu Mok
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2020
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30. Clinical Usefulness of HLA-B∗58:01 Genotyping in Gouty Arthritis
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Carrel Ka Lung Yu and Chi Chiu Mok
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hla-b∗58:01 ,allopurinol ,hypersensitivity ,severe cutaneous adverse reactions ,cost-effectiveness ,genetic screening ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Allopurinol is an effective urate lowering agent but may lead to rare but life-threatening severe cutaneous adverse reactions (SCAR). Genetic predisposition, age, sex, renal function, dosage and concomitant diuretic use are known risk factors of allopurinol related SCAR. Among these factors, HLA-B∗58:01 confers the highest risk. Frequency of the HLA-B∗58:01 allele varies significantly across different ethnic groups. Although the usefulness of HLA-5801 genotyping before initiation of allopurinol has been confirmed by clinical studies, its positive predictive value for SCAR is low because of the low prevalence of HLA-5801 in some localities. Thus, health economic analysis does not consistently show cost-effectiveness of universal screening of HLA-5801 before initiation of allopurinol. However, screening of this genotype in high-risk subjects, including those with renal impairment or advanced age, should be considered on individual basis.
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- 2019
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31. Management of Psychosis in Neuropsychiatric Lupus
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Di Kang and Chi Chiu Mok
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systemic lupus erythematosus ,neuropsychiatric lupus ,lupus psychosis ,corticosteroid-induced psychosis ,cyclophosphamide ,rituximab ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Acute psychosis is an uncommon but well-recognized manifestation of NPSLE. With no specific biomarkers to date, the diagnosis of NPSLE relies on clinical acumen for circumstantial evidence and exclusion of important differential diagnoses. The attribution of psychosis to NPSLE is facilitated by the application attribution models. In particular, the American College of Rheumatology nomenclature, Systemic Lupus International Collaborating Clinics attribution models and Italian algorithm for the attribution of psychosis to NPSLE are revisited. The mainstay of treatment for psychosis attributable to NPSLE is immunosuppression and symptomatic control. In refractory cases, immunomodulatory and emerging biological agents may be considered. This article reviews the diagnostic dilemma, pathogenic mechanisms and treatment of psychosis in SLE patients.
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- 2019
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32. Herpes zoster vaccination in systemic lupus erythematosus: the current status
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Chi Chiu Mok
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vaccine ,herpes ,zoster ,lupus ,complication ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Among the inflammatory rheumatic diseases, SLE is associated with the highest risk of herpes zoster reactivation relative to age. The reported incidence of herpes zoster infection in SLE ranges from 6.4 to 91.4/1000 patient-years, with main risk factors being major organ disease, immunosuppressive and biological therapies. Although herpes zoster in SLE is manageable with anti-viral treatment, complications such as superimposed bacterial infection, post-herpetic neuralgia may ensue. The low rate of herpes zoster vaccination in SLE is related to the lack of awareness, fear of the risk of vaccine-induced infection and disease flare, cost, as well as the lack of explicit recommendations of vaccine use for the paucity of data in immunocompromised and younger subjects. The recent availability of the non-live subunit and inactivated herpes zoster vaccines has provided more opportunities for SLE patients to be protected against this viral infection. More clinical trials are clearly needed in SLE to confirm safety, immunogenicity and efficacy of the herpes zoster vaccines.
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- 2019
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33. Trend of Survival of a Cohort of Chinese Patients With Systemic Lupus Erythematosus Over 25 Years
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Chi Chiu Mok, Ling Yin Ho, Kar Li Chan, Sau Mei Tse, and Chi Hung To
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damage ,lupus ,mortality ,time trend ,morbidity ,Medicine (General) ,R5-920 - Abstract
Objectives: To revisit the trend of survival of systemic lupus erythematosus in a cohort of Chinese patients over 25 years.Methods: Patients who fulfilled the 1997 ACR criteria for SLE and were followed in our hospital since 1995 were included. Patients were stratified into two groups according to the year of diagnosis: (1) 1995–2004 and (2) 2005–2018. Survival of patients was studied by Kaplan–Meier analysis. Organ damage as assessed by the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) and causes of death in the first 10 years of SLE onset was compared between the two groups. Cox regression was used to study factors associated with survival.Results: A total of 1,098 SLE patients were registered in our database. After excluding 157 patients diagnosed outside the time period of 1995–2018, 941 patients were studied (92% women). All were ethnic Chinese. The mean age of SLE onset was 35.1 ± 14.4 years, and the mean duration of observation was 13.1 ± 6.6 years. Seventy-seven (8.2%) patients were lost to follow-up. Groups 1 and 2 consisted of 364 and 577 patients, respectively. The mean SDI score at 10 years of disease onset was significantly higher in group 1 than group 2 patients (1.01 ± 1.43 vs. 0.57 ± 0.94; p < 0.01), particularly in the neuropsychiatric, musculoskeletal, and gonadal domains. Within 10 years of SLE onset, 32 (8.8%) patients in group 1 and 25 (4.3%) patients in group 2 died (p = 0.005). The 5- and 10-year cumulative survival rates were 93.6 and 91.0% in group 1 and 96.5 and 94.2% in group 2 patients, respectively (log-rank test p = 0.048). Infection accounted for more than half of the deaths in both groups. More group 1 than group 2 patients died of vascular events, but the difference was not statistically significant. Cox regression showed that the age of SLE onset and damage score accrued at 10 years, but not the time period in which SLE was diagnosed, were significantly associated with mortality.Conclusions: The improvement in survival of our SLE patients is probably related to the accrual of less organ damage in the past 15 years.
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- 2020
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34. Association of Urine sCD163 With Proliferative Lupus Nephritis, Fibrinoid Necrosis, Cellular Crescents and Intrarenal M2 Macrophages
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Ting Zhang, Hao Li, Kamala Vanarsa, Gabriel Gidley, Chi Chiu Mok, Michelle Petri, Ramesh Saxena, and Chandra Mohan
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CD163 ,lupus nephritis ,urine biomarker ,renal pathology ,activity index ,Immunologic diseases. Allergy ,RC581-607 - Abstract
CD163 is a marker for alternatively activated macrophages, which have been implicated in the pathogenesis of lupus nephritis (LN). In our preliminary screening of urine proteins in LN, urine soluble CD163 (sCD163) was significantly elevated in patients with active LN. To evaluate the potential of sCD163 as a biomarker in LN, urine sCD163 was assayed in patients with active LN, active non-renal lupus patients (ANR), inactive SLE and healthy controls (HC), using ELISA and normalized to urine creatinine. The correlation of urine sCD163 with clinical parameters and renal pathological attributes was further investigated in LN patients with concurrent renal biopsies. A total of 228 SLE patients and 56 HC were included from three cohorts. Results demonstrated that urine sCD163 was significantly elevated in active LN when compared with HC, inactive SLE, or ANR in African-American, Caucasian and Asian subjects (all P < 0.001). In LN patients with concurrent renal biopsies, urine sCD163 was significantly increased in patients with proliferative LN when compared with non-proliferative LN (P < 0.001). Urine sCD163 strongly correlated with SLEDAI, rSLEDAI, activity index (AI) of renal pathology, fibrinoid necrosis, cellular crescents, and interstitial inflammation on biopsies (all P < 0.01). Macrophages, particularly M2 macrophages, the predominant cells expressing CD163 within LN kidneys, represented a potential source of elevated urine sCD163, based on single-cell RNA sequencing analysis. To conclude, urine sCD163 discriminated patients with active LN from other SLE patients and was significantly elevated in proliferative LN. It strongly correlated with concurrent AI and several specific pathological attributes, demonstrating its potential in predicting renal pathology.
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- 2020
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35. Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis
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Chi Chiu Mok, Samar Soliman, Ling Yin Ho, Fatma A. Mohamed, Faten Ismail Mohamed, and Chandra Mohan
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Biomarker ,Lupus ,Nephritis ,Adhesion molecule ,Anti-angiogenic ,Chemokine ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). Method Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested. Results Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup. Conclusions Urinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.
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- 2018
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36. Effectiveness and tolerability of transdermal buprenorphine patches: a multicenter, prospective, open-label study in Asian patients with moderate to severe chronic musculoskeletal pain
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Do Heum Yoon, Seong-Il Bin, Simon Kin-Cheong Chan, Chun Kee Chung, Yong In, Hyoungmin Kim, Juan Javier Lichauco, Chi Chiu Mok, Young-Wan Moon, Tony Kwun-Tung Ng, Ester Gonzales Penserga, Dong Ah Shin, Dora You, and Hanlim Moon
- Subjects
Transdermal buprenorphine ,Asian ,Chronic non-malignant pain ,Musculoskeletal ,Pain score ,Quality of life ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background We examined the effectiveness and tolerability of transdermal buprenorphine (TDB) treatment in real-world setting in Asian patients with musculoskeletal pain. Methods This was an open-label study conducted in Hong Kong, Korea, and the Philippines between June 2013 and April 2015. Eligible patients fulfilled the following criteria: 18 to 80 years of age; clinical diagnosis of osteoarthritis, rheumatoid arthritis, low back pain, or joint/muscle pain; chronic non-malignant pain of moderate to severe intensity (Box-Scale-11 [BS-11] pain score ≥ 4), not adequately controlled with non-opioid analgesics and requiring an opioid for adequate analgesia; and no prior history of opioid treatment. Patients started with a 5 μg/h buprenorphine patch and were titrated as necessary to a maximum of 40 μg/h over a 6-week period to achieve optimal pain control. Patients continued treatment with the titrated dose for 11 weeks. The primary efficacy endpoint was the change in BS-11 pain scores. Other endpoints included patients’ sleep quality and quality of life as assessed by the 8-item Global Sleep Quality Assessment Scale (GSQA) questionnaire and the EuroQol Group 5-Dimension Self-Report Questionnaire-3 Level version (EQ-5D-3 L), respectively. Tolerability was assessed by collecting adverse events. Results A total of 114 eligible patients were included in the analysis. The mean BS-11 score at baseline was 6.2 (SD 1.6). Following initiation of TDB, there was a statistically significant improvement in BS-11 score from baseline to visit 3 (least squares [LS] mean change: -2.27 [95% CI -2.66 to −1.87]), which was maintained till the end of the study (visit 7) (LS mean change: −2.64 [95% -3.05 to −2.23]) (p
- Published
- 2017
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37. Author Correction: Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities
- Author
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Samantha Stanley, Kamala Vanarsa, Samar Soliman, Deena Habazi, Claudia Pedroza, Gabriel Gidley, Ting Zhang, Shree Mohan, Evan Der, Hemant Suryawanshi, Thomas Tuschl, Jill Buyon, Chaim Putterman, Chi Chiu Mok, Michelle Petri, Ramesh Saxena, and Chandra Mohan
- Subjects
Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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38. Correction: The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.
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Robert J Moots, Ricardo M Xavier, Chi Chiu Mok, Mahboob U Rahman, Wen-Chan Tsai, Mustafa H Al-Maini, Karel Pavelka, Ehab Mahgoub, Sameer Kotak, Joan Korth-Bradley, Ron Pedersen, Linda Mele, Qi Shen, and Bonnie Vlahos
- Subjects
Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0175207.].
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- 2017
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39. The impact of anti-drug antibodies on drug concentrations and clinical outcomes in rheumatoid arthritis patients treated with adalimumab, etanercept, or infliximab: Results from a multinational, real-world clinical practice, non-interventional study.
- Author
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Robert J Moots, Ricardo M Xavier, Chi Chiu Mok, Mahboob U Rahman, Wen-Chan Tsai, Mustafa H Al-Maini, Karel Pavelka, Ehab Mahgoub, Sameer Kotak, Joan Korth-Bradley, Ron Pedersen, Linda Mele, Qi Shen, and Bonnie Vlahos
- Subjects
Medicine ,Science - Abstract
OBJECTIVE:To assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes. METHODS:This multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6-24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected. RESULTS:Baseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low. CONCLUSION:ADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA. TRIAL REGISTRATION:This study was registered on www.ClinicalTrials.gov (NCT01981473).
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- 2017
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40. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus.
- Author
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Wanling Yang, Nan Shen, Dong-Qing Ye, Qiji Liu, Yan Zhang, Xiao-Xia Qian, Nattiya Hirankarn, Dingge Ying, Hai-Feng Pan, Chi Chiu Mok, Tak Mao Chan, Raymond Woon Sing Wong, Ka Wing Lee, Mo Yin Mok, Sik Nin Wong, Alexander Moon Ho Leung, Xiang-Pei Li, Yingyos Avihingsanon, Chun-Ming Wong, Tsz Leung Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Yuk Kwan Chang, Philip H Li, Ruo-Jie Li, Lu Zhang, Wilfred Hing Sang Wong, Irene Oi Lin Ng, Chak Sing Lau, Pak Chung Sham, Yu Lung Lau, and Asian Lupus Genetics Consortium
- Subjects
Genetics ,QH426-470 - Abstract
Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10(-11), OR = 1.29; WDFY4: rs7097397, P = 8.15x10(-12), OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.
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- 2010
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41. The Hong Kong Society of Rheumatology Consensus Recommendations for COVID-19 Vaccination in Adult Patients with Autoimmune Rheumatic Diseases
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Ronald Man Lung Yip, Chi Chiu Mok, and Ho So
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0301 basic medicine ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,rheumatology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,vaccine ,Medicine ,030203 arthritis & rheumatology ,Adult patients ,business.industry ,autoimmune ,RC581-607 ,vaccination ,Rheumatology ,Vaccination ,030104 developmental biology ,covid-19 ,consensus ,recommendations ,rheumatic ,Immunologic diseases. Allergy ,business - Abstract
Patients with autoimmune rheumatic diseases are potentially at risk of more serious Coronavirus Disease 2019 (COVID-19) infection and increased mortality due to immunosuppressive therapies and disease-related medical comorbidities. Uncertainty about the safety and efficacy of the COVID-19 vaccines is a major deterrent for patients to participate in the vaccination program. The Hong Kong Society of Rheumatology took the lead to publish a set of consensus statements for COVID-19 vaccination in adult patients with autoimmune rheumatic diseases through a Delphi exercise that involved the senior members of the Society. This serves as a guide to rheumatologists and other specialists, nurses, healthcare professionals, and public regarding COVID-19 vaccination in autoimmune rheumatic diseases.
- Published
- 2021
42. Risk and Factors associated with disease manifestations in systemic lupus erythematosus - lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients.
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Chan, Shirley C. W., Yong-Fei Wang, Yap, Desmond Y. H., Tak Mao Chan, Yu Lung Lau, Lee, Pamela P. W., Wai Ming Lai, Ying, Shirley K. Y., Tse, Niko K. C., Leung, Alexander M. H., Chi Chiu Mok, Ka Lai Lee, Li, Teresa W. L., Tsang, Helen H. L., Yeung, Winnie W. Y., Ho, Carmen T. K., Wong, Raymond W. S., Wanling Yang, Chak Sing Lau, and Li, Philip H.
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LUPUS nephritis ,SYSTEMIC lupus erythematosus ,DISEASE risk factors ,PANEL analysis ,AGE of onset ,REGRESSION analysis - Abstract
Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Methods: Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. Results: A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0 70). Conclusion: By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required. [ABSTRACT FROM AUTHOR]
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- 2023
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43. Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities
- Author
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Claudia Pedroza, Shree Mohan, Chaim Putterman, Ting Zhang, Evan Der, Deena Habazi, Kamala Vanarsa, Gabriel Gidley, Hemant Suryawanshi, Thomas Tuschl, Samar Soliman, Michelle Petri, Samantha Stanley, Ramesh Saxena, Chandra Mohan, Jill P. Buyon, and Chi Chiu Mok
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Science ,Urinary system ,Aptamer ,Lupus nephritis ,General Physics and Astronomy ,Urine ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,lcsh:Science ,ALCAM ,030203 arthritis & rheumatology ,Multidisciplinary ,Systemic lupus erythematosus ,business.industry ,Hemopexin ,General Chemistry ,medicine.disease ,030104 developmental biology ,Properdin ,lcsh:Q ,business - Abstract
Emerging urinary biomarkers continue to show promise in evaluating lupus nephritis (LN). Here, we screen urine from active LN patients for 1129 proteins using an aptamer-based platform, followed by ELISA validation in two independent cohorts comprised of 127 inactive lupus, 107 active LN, 67 active non-renal lupus patients and 74 healthy controls, of three different ethnicities. Urine proteins that best distinguish active LN from inactive disease are ALCAM, PF-4, properdin, and VCAM-1 among African-Americans, sE-selectin, VCAM-1, BFL-1 and Hemopexin among Caucasians, and ALCAM, VCAM-1, TFPI and PF-4 among Asians. Most of these correlate significantly with disease activity indices in the respective ethnic groups, and surpass conventional metrics in identifying active LN, with better sensitivity, and negative/positive predictive values. Several elevated urinary molecules are also expressed within the kidneys in LN, based on single-cell RNAseq analysis. Longitudinal studies are warranted to assess the utility of these biomarkers in tracking lupus nephritis. Developing noninvasive diagnostic biomarkers for lupus nephritis (LN) diagnosis is an important clinical goal. Here the authors identify urinary proteins correlated with active LN and disease severity, which differ across ethnicities but collectively outperform the current clinical method.
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- 2020
44. Management of glucocorticoid-related osteoporotic vertebral fracture
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Chi Chiu Mok and Stella Pui Yan Wong
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0301 basic medicine ,medicine.medical_specialty ,FRAX ,lcsh:Diseases of the musculoskeletal system ,medicine.medical_treatment ,Osteoporosis ,030209 endocrinology & metabolism ,Review Article ,Percutaneous vertebroplasty ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Teriparatide ,Medicine ,Fragility ,Risk factor ,Glucocorticoids ,business.industry ,medicine.disease ,Surgery ,Denosumab ,medicine.anatomical_structure ,Vertebral fracture ,030101 anatomy & morphology ,lcsh:RC925-935 ,business ,Vertebral column ,medicine.drug - Abstract
The vertebral column is the most common site of osteoporotic fractures in long-term users of glucocorticoids. Vertebral fracture leads to significant morbidities such as unrelenting pain, spinal deformities and reduced mobility, leading to diminished quality of life. Epidemiological data on the prevalence of glucocorticoid-induced vertebral fractures are limited. As vertebral fracture is a strong risk factor for further fragility fractures and mortality, it should be treated appropriately. This article reviews recent data on the prevalence of vertebral fractures in glucocorticoid users, fracture risk stratification, and evidence-based treatment options. The risk of osteoporotic fractures estimated by FRAX should be adjusted for glucocorticoid users. The first-line treatment of glucocorticoid-induced osteoporosis remains the bisphosphonates. Teriparatide and denosumab are alternative options. Percutaneous vertebroplasty and kyphoplasty may be considered for symptomatic control of acute vertebral fracture-related pain when conservative measures fail. Keywords: Glucocorticoids, Vertebral fracture, Fragility, Osteoporosis
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- 2020
45. Update on Symptomatic Treatment of Acute Vertebral Compression Fracture
- Author
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Chi Chiu Mok and Stella Pui Yan Wong
- Subjects
lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,business.industry ,Vertebral compression fracture ,Symptomatic treatment ,Osteoporosis ,medicine.disease ,vertebral ,osteoporosis ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,kyphoplasty ,fracture ,Fracture (geology) ,Medicine ,vertebroplasty ,Osteoporotic fracture ,030212 general & internal medicine ,business ,lcsh:RC581-607 ,030217 neurology & neurosurgery ,Vertebral column - Abstract
The vertebral column is the most common site of osteoporotic fracture in older individuals and in those using long-term glucocorticoids. Vertebral compression fracture leads to significant morbidities such as acute and chronic pain, spinal deformities and neurological complications, resulting in reduced mobility and quality of life. As a previous vertebral compression fracture is a strong risk factor for further fragility fractures and mortality, it should be treated appropriately. This article reviews the management of osteoporotic vertebral compression fracture and provides evidence-based treatment options.
- Published
- 2019
46. Does hydroxychloroquine improve patient reported outcomes in patients with lupus?
- Author
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Sandra V. Navarra, Luis M. Vilá, Ivana Blazevic, Daniel J. Wallace, Karina D. Torralba, Vinay Sehgal, Shilpa Arora, Hervé Devilliers, Aman Sharma, Sarfaraz Hasni, Benzeeta Pinto, Josiane Bourré-Tessier, Davide Mazzoni, Elvira Cicognani, Ana M. Bertoli, Chi Chiu Mok, Meenakshi Jolly, Berna Goker, Michael H. Weisman, Ann E. Clarke, Mitsuyo Inoue, Ioana Moldovan, Sergio Toloza, Desiree R. Azizoddin, Seminur Haznedaroglu, and Meenakshi Jolly, Vinay Sehgal, Shilpa Arora, Desiree Azizoddin, Benzeeta Pinto, Aman Sharma, Herve Devilliers, Mitsuyo Inoue, Sergio Toloza, Ana Bertoli, Ivana Blazevic, Luis M Vila, Ioana Moldovan, Karina D Torralba, Davide Mazzoni, Elvira Cicognani, Sarfaraz Hasni, Berna Goker, Seminur Haznedaroglu, Josiane Bourre-Tessier, Sandra V Navarra, Ann Clarke, Michael Weisman, Daniel Wallace, Chi Chiu Mok
- Subjects
Adult ,Male ,medicine.medical_specialty ,Databases, Factual ,Improved survival ,Disease activity ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Quality of life ,Internal medicine ,Medicine ,Humans ,Lupus Erythematosus, Systemic ,In patient ,030212 general & internal medicine ,Patient Reported Outcome Measures ,Quality of life, systemic lupus erythematosus, disease activity, damage, hydroxychloroquine ,030203 arthritis & rheumatology ,Systemic lupus erythematosus ,business.industry ,Hydroxychloroquine ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Antirheumatic Agents ,Quality of Life ,Female ,business ,medicine.drug - Abstract
Background Hydroxychloroquine (HCQ) use is associated with less disease activity, flares, damage and improved survival in Systemic Lupus Erythematosus (SLE). However, its effect on patient reported health outcomes (PROs) such as quality of life (QOL) is not known. Methods International data from Study on Outcomes of Lupus (SOUL) from 2,161 SLE patients were compared by HCQ use. Disease activity and damage were assessed using SELENA-SLEDAI and SLICC-ACR/SDI. QOL was evaluated using LupusPRO and Lupus Impact Tracker (LIT). Linear regression analyses were performed with LupusPRO summary scores health related HRQOL, non-health related NHRQOL and LIT as dependent and HCQ use as independent variable. Analyses were undertaken to test mediation of effects of HCQ use on QOL through disease activity. Results Mean age was 40.5 ± 12.8 years, 93% were women. Sixty-three (1363/2161) percent were on HCQ. On univariate analysis, HCQ use was associated with (a) better QOL (LupusPRO-HRQOL: β 6.19, 95% CI 4.15, 8.24, P ≤ 0.001, LupusPRO NHRQOL: β 5.83, 95% CI 4.02, 7.64, P ≤ 0.001) and less impact on daily life (LIT: β −9.37, 95% CI −12.24, −6.50, P ≤ 0.001). On multivariate and mediational analyses, the effects of HCQ on QOL were indirectly and completely mediated through disease activity. Conclusions HCQ use in SLE is associated with better patient reported health outcomes (LupusPRO-HRQOL and NHRQOL and impact on daily life), and the effects are mediated through disease activity. This information can facilitate patients and physician’s communication with decision-making regarding the use of HCQ for SLE management.
- Published
- 2021
47. The Performance of the Hospital Anxiety and Depression Scale for Screening of Anxiety and Depressive Disorders in Chinese Patients with Rheumatoid Arthritis in Hong Kong.
- Author
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Yung Ching Lok, Eugenia and Chi Chiu Mok
- Subjects
- *
RHEUMATOID arthritis , *HOSPITAL patients , *ANXIETY , *MENTAL illness , *MENTAL depression - Published
- 2022
- Full Text
- View/download PDF
48. Clinical Usefulness of HLA-B∗58:01 Genotyping in Gouty Arthritis
- Author
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Chi Chiu Mok and Carrel Ka Lung Yu
- Subjects
hla-b∗58:01 ,lcsh:Immunologic diseases. Allergy ,Cost effectiveness ,Allopurinol ,Renal function ,severe cutaneous adverse reactions ,allopurinol ,03 medical and health sciences ,0302 clinical medicine ,Genetic predisposition ,medicine ,030212 general & internal medicine ,Gouty arthritis ,Genotyping ,cost-effectiveness ,030203 arthritis & rheumatology ,business.industry ,Process Chemistry and Technology ,genetic screening ,HLA-B ,Fuel Technology ,Immunology ,Economic Geology ,hypersensitivity ,business ,lcsh:RC581-607 ,medicine.drug - Abstract
Allopurinol is an effective urate lowering agent but may lead to rare but life-threatening severe cutaneous adverse reactions (SCAR). Genetic predisposition, age, sex, renal function, dosage and concomitant diuretic use are known risk factors of allopurinol related SCAR. Among these factors, HLA-B[Formula: see text]58:01 confers the highest risk. Frequency of the HLA-B[Formula: see text]58:01 allele varies significantly across different ethnic groups. Although the usefulness of HLA-5801 genotyping before initiation of allopurinol has been confirmed by clinical studies, its positive predictive value for SCAR is low because of the low prevalence of HLA-5801 in some localities. Thus, health economic analysis does not consistently show cost-effectiveness of universal screening of HLA-5801 before initiation of allopurinol. However, screening of this genotype in high-risk subjects, including those with renal impairment or advanced age, should be considered on individual basis.
- Published
- 2019
49. The Hong Kong Society of Rheumatology Biologics Registry: Updated Report (Nov 2018)
- Author
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Rhonda Wan and Chi Chiu Mok
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2018
50. Exploring urine:serum fractional excretion ratios as potential biomarkers for lupus nephritis.
- Author
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Soliman, Samar A., Stanley, Samantha, Vanarsa, Kamala, Ismail, Faten, Chi Chiu Mok, and Mohan, Chandra
- Subjects
LUPUS nephritis ,EXCRETION ,SYSTEMIC lupus erythematosus ,BIOMARKERS ,BLOOD proteins - Abstract
Objectives: The goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE). Methods: Thirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings. Results: The FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1
FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE , PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE , PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE , PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE. Conclusions: With most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
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