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Kanjanasirirat P, Jearawuttanakul K, Seemakhan S, Borwornpinyo S, Wongtrakoongate P, Hongeng S, Charoensutthivarakul S. High-throughput screening of FDA-approved drugs identifies colchicine as a potential therapeutic agent for atypical teratoid/rhabdoid tumors (AT/RTs). RSC Adv 2025; 15:12331-12341. [PMID: 40248220 PMCID: PMC12004362 DOI: 10.1039/d5ra01341k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Accepted: 04/03/2025] [Indexed: 04/19/2025] Open
Abstract
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive tumor of the primary central nervous system primarily affecting children. It typically originates in the cerebellum and brain stem and is associated with a low survival rate. While standard chemotherapy has been used as a primary treatment for AT/RTs, its success rate is unsatisfactory, and patients often experience severe side effects. Therefore, there is an urgent need to develop new and effective treatment strategies. One promising approach for identifying new therapies is drug repurposing. Although many FDA-approved drugs have been repurposed for various cancers, there have been no reports of such applications for AT/RTs. In this study, a library of 2130 FDA-approved drugs was screened using a high-throughput screening system against 2D traditional cultures and 3D spheroid cultures of AT/RT cell lines (BT-12 and BT-16). From this screening, colchicine, a non-chemotherapeutic agent, was identified as a promising candidate. It exhibited IC50 values of 0.016 and 0.056 μM against 2D BT-12 and 2D BT-16 cells, respectively, and IC50 values of 0.004 and 0.023 μM against 3D BT-12 and BT-16 spheroid cultures. Additionally, the cytotoxic effects of colchicine on human brain endothelial cells and human astrocytes were evaluated, and CC50 > 20 μM was observed, which is over two orders of magnitude higher than its effective concentrations in AT/RT cells, indicating considerably lower toxicity to normal brain cells and brain endothelial cells. In conclusion, colchicine shows significant potential to be repurposed as a treatment for AT/RTs, providing a safer and more effective therapeutic option for this rare and challenging disease.
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Affiliation(s)
- Phongthon Kanjanasirirat
- School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University Bangkok 10400 Thailand +66-2-201-5899
- Department of Pathobiology, Faculty of Science, Mahidol University Bangkok 10400 Thailand
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
| | - Kedchin Jearawuttanakul
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
| | - Sawinee Seemakhan
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
| | - Suparerk Borwornpinyo
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
- Department of Biotechnology, Faculty of Science, Mahidol University Bangkok 10400 Thailand
| | - Patompon Wongtrakoongate
- Department of Biochemistry, Faculty of Science, Mahidol University Bangkok 10400 Thailand
- Center for Neuroscience, Faculty of Science, Mahidol University Bangkok 10400 Thailand
| | - Suradej Hongeng
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
- Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok 10400 Thailand
| | - Sitthivut Charoensutthivarakul
- School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University Bangkok 10400 Thailand +66-2-201-5899
- Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University Bangkok 10400 Thailand
- Center for Neuroscience, Faculty of Science, Mahidol University Bangkok 10400 Thailand
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Saag KG, Dalbeth N, Hsu CY, Kuo CF, Nuki G, Perez-Ruiz F, White WB, Hariri A, Lee Y, Jang Y, Han S, Choi HK. Evaluation of the efficacy and safety of a novel xanthine oxidase inhibitor, tigulixostat, in gout patients with hyperuricemia: Design of the EURELIA 1 and EURELIA 2 studies. Contemp Clin Trials 2025; 151:107843. [PMID: 39929260 DOI: 10.1016/j.cct.2025.107843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/20/2025] [Accepted: 02/05/2025] [Indexed: 02/19/2025]
Abstract
BACKGROUND Gout is a chronic disease of monosodium urate crystal deposition caused by elevated serum urate (SU). Gout may progress from acute episodic attacks to a disabling chronic deforming arthropathy. Allopurinol and febuxostat are the most widely prescribed urate-lowering drugs, however, these agents have potential adverse events and are seldom titrated to achieve a target SU level. Tigulixostat is a novel non-purine selective xanthine oxidase inhibitor for gout with hyperuricemia which has demonstrated potent in vitro and in vivo urate lowering activity and is being further investigated in humans for regulatory approvals. METHODS The Phase 3 program for tigulixostat consists of two clinical trials: EURELIA 1 and EURELIA 2. EURELIA 1 is a randomized, multi-regional, double-blind, parallel-group, placebo-controlled study to assess the safety and efficacy of 6 months of tigulixostat (100, 200, or 300 mg) in gout patients with hyperuricemia (n = 350). EURELIA 2 is a randomized, multi-regional, double-blind, double-dummy, parallel-group, active comparator (allopurinol titrated up to 800 mg) and placebo-controlled study to assess the safety and efficacy of tigulixostat (100, 200, or 300 mg) up to 12 months in gout patients with hyperuricemia (n = 2542). The primary endpoint for both studies is to determine the proportion of patients with SU levels <6.0 mg/dL sustained at for 3 months (Months 4, 5, and 6). CONCLUSIONS EURELIA 1 and EURELIA 2 studies will be able to adequately determine the efficacy and safety of tigulixostat compared to both placebo and allopurinol. TRIAL REGISTRATION NUMBER For EURELIA 1, the clinicaltrials.gov identifier is NCT05586958. For EURELIA 2, the clinicaltrials.gov identifier is NCT05586971 and the EU CT number is 2022-501421-20-00. The sponsor for both trials is LG Chem, Ltd. (Seoul, South Korea).
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Affiliation(s)
- Kenneth G Saag
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, AL, USA
| | - Nicola Dalbeth
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Chi-Yuan Hsu
- Division of Nephrology, University of California-San Francisco, San Francisco, CA, USA
| | - Chang-Fu Kuo
- Chang Gung Memorial Hospital, Lin-Kou Medical Center, Taoyuan, Taiwan
| | - George Nuki
- University of Edinburgh Centre for Genomics and Experimental Medicine, Western General Hospital, Edinburgh, UK
| | - Fernando Perez-Ruiz
- Osakidetza, OSI-EEC, Cruces University Hospital, Rheumatology Division, Department of Medicine, Medicine and Nursing School, University of the Basque Country, Vizcaya, Spain
| | - William B White
- Calhoun Cardiology Center at the University of Connecticut School of Medicine, Farmington, CT, USA
| | - Ali Hariri
- Clinical & Regulatory Affairs Center, Life Science, LG Chem, Ltd., Seoul, Republic of Korea
| | - Yunjung Lee
- Clinical & Regulatory Affairs Center, Life Science, LG Chem, Ltd., Seoul, Republic of Korea
| | - Younghwan Jang
- Clinical & Regulatory Affairs Center, Life Science, LG Chem, Ltd., Seoul, Republic of Korea
| | - Song Han
- Clinical & Regulatory Affairs Center, Life Science, LG Chem, Ltd., Seoul, Republic of Korea
| | - Hyon K Choi
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
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Audet T, Picard-Turcot MA, Robindaine J, Carrier N, Dagenais P. Improving Gout Care in a Canadian Academic Medical Center Through a Multidisciplinary, Nurse-Led Protocol. J Rheumatol 2025; 52:285-289. [PMID: 39617409 DOI: 10.3899/jrheum.2024-0707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/08/2024] [Indexed: 12/18/2024]
Abstract
OBJECTIVE Following Health Canada's knowledge translation framework, we report the results of a clinical audit from 2012 to 2015 followed by a multidisciplinary, nurse-led gout care protocol with a treat-to-target (T2T) strategy implemented in April 2018. METHODS A clinical audit with chart reviewing was completed for adults with gout and urate-lowering therapy (ULT) indication at the Centre Hospitalier Universitaire de Sherbrooke. A nurse-led treatment algorithm using allopurinol was then developed. Titration of ULT by a nurse every 4 weeks was done until serum uric acid (SUA) target. In the postprotocol implementation, adults with gout and ULT indication were retrospectively recruited through a billing agency until December 2020. The main outcome was SUA target achievement at 6 months. RESULTS Of 50 patients identified in the audit, 31% reached SUA target at 6 months and 16% were lost to follow-up. A 74-patient postprotocol implementation cohort was recruited, with 43 in the protocol group and 31 under usual care. Most prevalent ULT indication was ≥ 2 gout attacks per year (n = 52) at 70%. Target SUA was reached in 65% (n = 28) in the protocol group at 6 months compared to 19% (n = 6) in the usual care group (P < 0.001). Failing to titrate medication in the usual care group was the leading cause for nonachievement of SUA target at 6 months. Five percent of patients were lost to follow-up, all in the usual care group. CONCLUSION A multidisciplinary, nurse-led protocol with a T2T strategy implemented after a clinical audit significantly improved gout care. Such protocol could be replicated elsewhere in Canada.
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Affiliation(s)
- Thomas Audet
- T. Audet, MD, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke;
| | - Marie-Aude Picard-Turcot
- M.A. Picard-Turcot, MD, Family Physician Residency Training Program, Faculty of Medicine, Université de Montréal, Montreal
| | - Julie Robindaine
- J. Robindaine, BSc, NP, Centre Intégré Universitaire de Santé et de Services Sociaux de l'Estrie-Centre Hospitalier Universitaire de Sherbrooke (CHUS), Department of Medicine, Rheumatology Division, Université de Sherbrooke, Sherbrooke
| | - Nathalie Carrier
- N. Carrier, MSc, Centre de Recherche du CHUS, Rheumatic Disease Unit, Université de Sherbrooke, Sherbrooke
| | - Pierre Dagenais
- P. Dagenais, MD, PhD, Department of Medicine, Rheumatology Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
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Wang Y, Zhang Y, Yu Z, Bai Y, Zhu M, Lei Y, Dong B, Zhang Q, Gu Q, Xiang J. Developing Monosodium Urate Monohydrate Crystals-Induced Gout Model in Rodents and Rabbits. Curr Protoc 2025; 5:e70114. [PMID: 40145644 DOI: 10.1002/cpz1.70114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2025]
Abstract
Gout is a chronic disease caused by the deposition of monosodium urate monohydrate (MSU) crystals within the body, particularly in one or more joints, which can lead to sudden severe attacks of pain, swelling, redness, and tenderness, known as gout flares. Historically termed the "disease of kings," gout is one of the oldest joint diseases and remains the most common form of inflammatory arthritis haunting humans in the 21st century. It is associated with cardiovascular, metabolic, and renal comorbidities and can lead to reduced mobility and impaired physical function and contributing to work absenteeism. Given its increasing global incidence, novel therapies for gouty arthritis disease are urgently needed. Experimental gout models are indispensable tools for deciphering disease pathogenesis and evaluating the efficacy and side effect of newly developed therapeutics at preclinical stage. Herein, we described a series of highly reproducible acute gout flare and air pouch models in rodents and rabbits that can be used to address various scientific questions relevant to pathological changes and immune responses during and after a gout attack. Animal gout flare models, elicited by MSU crystals, mimic the main histopathological features of human gouty arthritis, including damage to cartilage and joint swelling. Meanwhile, air pouch models serve as a tool to evaluate robust inflammatory cytokine secretion and neutrophil infiltration. This article provides a detailed description of procedures and troubleshooting tips required to reproducibly induce gout flare and air pouch models in animals and critically evaluate the pathogenesis of the disease. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Preparation of monosodium urate crystalline Basic Protocol 2: Development of MSU-induced gout flare model in mice Support Protocol 1: Histological assessment of mouse ankle tissues Basic Protocol 3: Development of MSU-induced gout flare model in rats Basic Protocol 4: Development of MSU-induced gout flare model in rabbits Basic Protocol 5: Development and validation of reference articles in MSU-induced air pouch model in rats Basic Protocol 6: Development and validation of reference articles in MSU-induced air pouch model in mice Support Protocol 2: Flow cytometry of mouse neutrophils in air pouch lavage samples.
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Affiliation(s)
- Yufang Wang
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Ya Zhang
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Zhengrong Yu
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Yige Bai
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Mengxing Zhu
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Yan Lei
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Baoli Dong
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Qiyao Zhang
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Qingyang Gu
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
| | - Jian Xiang
- In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China
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Stamp LK, Frampton C, Newcomb JA, O'Dell JR, Mikuls TR, Dalbeth N. Gout Flares After Stopping Anti-Inflammatory Prophylaxis: A Rapid Literature Review and Meta-Analysis. Arthritis Care Res (Hoboken) 2024. [PMID: 39711080 DOI: 10.1002/acr.25486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 12/08/2024] [Accepted: 12/12/2024] [Indexed: 12/24/2024]
Abstract
OBJECTIVE The aim of this research was to determine how common gout flares are after ceasing anti-inflammatory prophylaxis. METHODS A rapid literature review and meta-analysis were undertaken. PubMed was searched from inception to February 2024. Eligibility criteria included any clinical trial of people with gout with at least one arm starting or intensifying urate-lowering therapy (ULT) with coprescription of anti-inflammatory prophylaxis and that had the percentage of participants experiencing one or more gout flares reported during and after the period of prophylaxis. Random effects meta-analyses were used to generate pooled estimates of the percentage of participants experiencing one or more flares in each period. RESULTS Six trials were included, together with aggregated, unpublished data from the VA STOP Gout trial (2,972 participants). Pooled random effects estimates of the percentage of participants having one or more gout flares were 14.7% (95% confidence interval [CI] 11.3-18.5%) during prophylaxis, 29.7% (95% CI 22.9-37.0%) in the three-month period after ceasing prophylaxis, and 12.2% (95% CI 6.8-19.0%) during the last study period. The mean difference in the percentage of participants having one or more gout flare while taking prophylaxis and immediately after ceasing prophylaxis was -14.8.0% (95% CI -21.2% to -8.5%; P < 0.0001). The mean difference from the period immediately following prophylaxis discontinuation compared to the last study period was 16.0% (P < 0.001). Sensitivity analyses indicated no material effects of prophylaxis duration, trial duration, ULT class, or placebo arms. CONCLUSION Gout flares are common after stopping anti-inflammatory prophylaxis but return to levels seen during prophylaxis. Patients should be cautioned about the risk of gout flares and have a plan for effective gout flare management in the three months after stopping anti-inflammatory prophylaxis.
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Affiliation(s)
- Lisa K Stamp
- University of Otago, Christchurch and Health New Zealand, Te Whatu Ora Waitaha, Christchurch, New Zealand
| | | | | | - James R O'Dell
- VA Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center, Omaha
| | - Ted R Mikuls
- VA Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center, Omaha
| | - Nicola Dalbeth
- Health New Zealand, Te Whatu Ora Te Toka Tumai, and the University of Auckland, Auckland, New Zealand
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Soricelli E, Quartararo G, Leuratti L, Schiavo L, Iannelli A, Facchiano E. Effects of bariatric surgery on hyperuricemia and gout: a systematic review of the literature. Updates Surg 2024:10.1007/s13304-024-02028-6. [PMID: 39520613 DOI: 10.1007/s13304-024-02028-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
Gout is the most common form of inflammatory arthritis, and it is due to the deposition of monosodium urate crystals in the articular and extra-articular tissues. Body mass index is strongly correlated with elevated serum uric acid levels and gout is often associated with obesity and metabolic syndrome. Recommended nonpharmacological treatments for hyperuricemia and gout include dietary modifications and weight loss. Many studies have demonstrated that weight loss could reduce serum urate in patients with obesity and it is a commonly recommended treatment for gout. Bariatric surgery-induced weight loss exerts beneficial effects on hyperuricemia and gout, even if a possible raise of gout flares can be observed in patients with hyperuricemia early after surgery. The aim of this review is to systematically analyze all the studies published so far reporting a link between hyperuricemia and/or gout and bariatric surgery to obtain reliable figures on the incidence of this disease and describe the mechanisms underlying this association. Eleven studies accounting for 11,256 patients were included in the review. Mean preoperative prevalence of gout was 4.1%, while the preoperative prevalence of hyperuricemia ranged from 30.6% to 58%. After a mean follow-up of 8.5 months, postoperative prevalence of gout significantly decreased to 2.9% (p < .007). The incidence of gout flares after bariatric surgery was higher in the early postoperative phase and progressively decreased over time. Similarly, serum uric acid concentrations showed an increase within the first postoperative month, which was followed by a progressive decrease below the preoperative value.
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Affiliation(s)
- Emanuele Soricelli
- Department of Surgery, General Metabolic and Bariatric Surgery Unit, Santa Maria Nuova Hospital, Piazza Santa Maria Nuova, 50122, Florence, Italy
| | - Giovanni Quartararo
- Department of Surgery, General Metabolic and Bariatric Surgery Unit, Santa Maria Nuova Hospital, Piazza Santa Maria Nuova, 50122, Florence, Italy
| | - Luca Leuratti
- Department of Surgery, General Metabolic and Bariatric Surgery Unit, Santa Maria Nuova Hospital, Piazza Santa Maria Nuova, 50122, Florence, Italy
| | - Luigi Schiavo
- Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana", University of Salerno, Salerno, Italy
| | - Antonio Iannelli
- Université Côte d'Azur, Nice, France
- Inserm, U1065, Team 8 'Hepatic Complications of Obesity and Alcohol', Nice, France
- ADIPOCIBLE Study Group, Nice, France
| | - Enrico Facchiano
- Department of Surgery, General Metabolic and Bariatric Surgery Unit, Santa Maria Nuova Hospital, Piazza Santa Maria Nuova, 50122, Florence, Italy.
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Tramujas L, Nogueira A, Felix N, de Barros E Silva PGM, Abizaid A, Cavalcanti AB. Association of colchicine use with cardiovascular and limb events in peripheral artery disease: Insights from a retrospective cohort study. Atherosclerosis 2024; 398:118563. [PMID: 39299823 DOI: 10.1016/j.atherosclerosis.2024.118563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 07/06/2024] [Accepted: 08/07/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND AND AIMS Colchicine has demonstrated efficacy in treating coronary artery disease, but its efficacy in peripheral artery disease (PAD) remains uncertain. This study aims to address this gap in knowledge. METHODS A retrospective cohort study was conducted using the TriNetX Network, selecting patients with lower limb PAD between January 1, 2011, and January 1, 2024. Colchicine users were matched 1:1 with non-users through propensity score matching, considering demographics, medical conditions, medications, and psychosocial factors. The primary outcome was a composite of major adverse cardiovascular and limb events (MACLE) - including lower limb amputation, revascularization for lower limb ischemia, acute myocardial infarction, ischemic stroke, and all-cause mortality - over a ten-year follow-up. RESULTS From 53,568 colchicine-treated and 1,499,969 untreated patients with lower limb PAD, 52,350 pairs were successfully matched. Over ten years, colchicine was associated with a significant reduction in MACLE (hazard ratio, [HR] 0.90, 95% CI 0.88-0.92, p < 0.001), any lower limb amputation (HR 0.84, 95% CI 0.75-0.94, p = 0.002), revascularization for lower limb ischemia (HR 0.85, 95% CI 0.82-0.88, p < 0.001), major adverse cardiovascular events (HR 0.93, 95% CI 0.91-0.95, p < 0.001), and all-cause mortality (HR 0.90, 95% CI 0.87-0.92, p < 0.001). It also result in a reduced risk of ischemic stroke (HR 0.95, 95% CI 0.92-0.98, p = 0.001), but not of acute myocardial infarction (HR 0.98, 95% CI 0.95-1.01, p = 0.24). CONCLUSIONS Colchicine significantly reduced major adverse cardiovascular and limb events in patients with lower limb PAD, supporting the need for further investigation.
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Affiliation(s)
| | - Alleh Nogueira
- Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil
| | - Nicole Felix
- Federal University of Campina Grande, Campina Grande, Brazil
| | | | - Alexandre Abizaid
- Hcor Research Institute, São Paulo, Brazil; Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
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Helget LN, Mikuls TR. Reply. Arthritis Rheumatol 2024; 76:1697-1698. [PMID: 38923299 DOI: 10.1002/art.42935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 06/20/2024] [Indexed: 06/28/2024]
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Barry A, Helget LN, Androsenko M, Wu H, Kramer B, Newcomb JA, Brophy MT, Davis-Karim A, England BR, Ferguson R, Pillinger MH, Neogi T, Palevsky PM, Merriman TR, O’Dell JR, Mikuls TR. Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial. Arthritis Rheumatol 2024; 76:1552-1559. [PMID: 38925627 PMCID: PMC11421957 DOI: 10.1002/art.42927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/06/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024]
Abstract
OBJECTIVE Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. METHODS This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. RESULTS Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. CONCLUSION These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.
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Affiliation(s)
- Austin Barry
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Lindsay N. Helget
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Maria Androsenko
- VA Boston Cooperative Studies Program Coordinating Center, Boston, Massachusetts, USA
| | - Hongsheng Wu
- VA Boston Cooperative Studies Program Coordinating Center, Boston, Massachusetts, USA
- Babson College, Wellesley, Massachusetts, USA
| | - Bridget Kramer
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Jeff A. Newcomb
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Mary T. Brophy
- VA Boston Cooperative Studies Program Coordinating Center, Boston, Massachusetts, USA
- School of Medicine, VA Boston Health Care System, Boston University, Boston, Massachusetts, USA
| | - Anne Davis-Karim
- VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center, Albuquerque, New Mexico, USA
| | - Bryant R. England
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Ryan Ferguson
- VA Boston Cooperative Studies Program Coordinating Center, Boston, Massachusetts, USA
- Boston University School of Medicine, Boston, Massachusetts, USA
| | - Michael H. Pillinger
- VA New York Harbor Health Care System, New York, New York, USA:
- New York University Grossman School of Medicine, New York, New York, USA
| | - Tuhina Neogi
- Boston University School of Medicine, Boston, Massachusetts, USA
| | - Paul M. Palevsky
- VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania, USA
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Tony R. Merriman
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - James R. O’Dell
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Ted R. Mikuls
- Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, Nebraska, USA
- Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA
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Zhuang Y, Pan B, Zhang Y, Tang Z, Ji X, Zhang S, Yao L, Li T, Ma W, Tan C, Luo Y. Structure-activity relationships of natural and synthetic lathyrane-based diterpenoids for suppression of NLRP3-driven inflammation and gouty arthritis. Bioorg Chem 2024; 150:107558. [PMID: 38878755 DOI: 10.1016/j.bioorg.2024.107558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 07/21/2024]
Abstract
Lathyrane-based diterpenoid is one of the critical bioactive elements of Euphorbia lathyris L., a widely used traditional Chinese medicine for the treatment of inflammation and infection. In this study, we introduced and evaluated seven synthetic or natural lathyrane-based diterpenoids with the same core structure but notable structural variations at specific positions, for their anti-inflammatory and gout-alleviating properties. There was no significant cytotoxicity below 10 μM among the initial test of the cell counting kit 8 of the seven candidate derivatives (compounds 13 to 19) in this work. Furthermore, maintaining the acyloxy group at 15-C position and the strongly hydrophobic aryl structure at 3-C and 5-C positions, compounds 15 (Euphorbia factor L3, EFL3) and 17 strikingly inhibited the production of IL-1β related to the actuation of the inflammasome in our study. The ELISA assay indicated that the anti-inflammatory effects of EFL3 were better associated with MSU stimulation than other second-line pathways triggered by inflammasome. Further examinations on the acute paw gout model in C57BL/6 mice showed that EFL3 had a significantly inflammatory retarding effect by intraperitoneal injection. It decreased swelling volume as well as the cleavage and activation of local IL-1β and casepas-1 in the paw. To conclude, our findings reveal several potential key structure-activity relationships that govern the anti-inflammatory effects of lathyrane-type diterpenoids, the dispensable acyl group at the 15-C position, the importance of maintaining the spatial structure of the B-ring, and the potential importance of hydrophobic substituents at the 3-C position. These insights may provide guidance for the structural design of lathyrane-type agents in the future; furthermore, we found that the lathyrane-based diterpenoid EFL3 is a potential agent for gout that is expected to provide a novel therapeutic strategy for inflammation intervention.
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Affiliation(s)
- Yuqing Zhuang
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bin Pan
- Shandong Engineering Research Center of Green and High-value Marine Fine Chemical, Weifang University of Science and Technology, Shouguang, China.
| | - Yuanyuan Zhang
- Sichuan Institute of Food Inspection, Chengdu, Sichuan, China
| | - Zhigang Tang
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xing Ji
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Sijun Zhang
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Lei Yao
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Tao Li
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wenjing Ma
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chunyu Tan
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
| | - Yubin Luo
- Department of Rheumatology & Immunology, Laboratory of Rheumatology and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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Wang S, Liu W, Wei B, Wang A, Wang Y, Wang W, Gao J, Jin Y, Lu H, Ka Y, Yue Q. Traditional herbal medicine: Therapeutic potential in acute gouty arthritis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 330:118182. [PMID: 38621464 DOI: 10.1016/j.jep.2024.118182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 03/27/2024] [Accepted: 04/08/2024] [Indexed: 04/17/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Acute gouty arthritis (AGA) is characterized by a rapid inflammatory reaction caused by the build-up of monosodium urate (MSU) crystals in the tissues surrounding the joints. This condition often associated with hyperuricemia (HUA), is distinguished by its symptoms of intense pain, active inflammation, and swelling of the joints. Traditional approaches in AGA management often fall short of desired outcomes in clinical settings. However, recent ethnopharmacological investigations have been focusing on the potential of Traditional Herbal Medicine (THM) in various forms, exploring their therapeutic impact and targets in AGA treatment. AIM OF THE REVIEW This review briefly summarizes the current potential pharmacological mechanisms of THMs - including active ingredients, extracts, and prescriptions -in the treatment of AGA, and discusses the relevant potential mechanisms and molecular targets in depth. The objective of this study is to offer extensive information and a reference point for the exploration of targeted AGA treatment using THMs. MATERIALS AND METHODS This review obtained scientific publications focused on in vitro and in vivo studies of anti-AGA THMs conducted between 2013 and 2023. The literature was collected from various journals and electronic databases, including PubMed, Elsevier, ScienceDirect, Web of Science, and Google Scholar. The retrieval and analysis of relevant articles were guided by keywords such as "acute gouty arthritis and Chinese herbal medicine," "acute gouty arthritis herbal prescription," "acute gouty arthritis and immune cells," "acute gouty arthritis and inflammation," "acute gouty arthritis and NOD-like receptor thermoprotein domain associated protein 3 (NLRP3)," "acute gouty arthritis and miRNA," and "acute gouty arthritis and oxidative stress." RESULTS We found that AGA has a large number of therapeutic targets, highlighting the effectiveness the potential of THMs in AGA treatment through in vitro and in vivo studies. THMs and their active ingredients can mitigate AGA symptoms through a variety of therapeutic targets, such as influencing macrophage polarization, neutrophils, T cells, natural killer (NK) cells, and addressing factors like inflammation, NLRP3 inflammasome, signaling pathways, oxidative stress, and miRNA multi-target interactions. The anti-AGA properties of THMs, including their active components and prescriptions, were systematically summarized and categorized based on their respective therapeutic targets. CONCLUSION phenolic, flavonoid, terpenoid and alkaloid compounds in THMs are considered the key ingredients to improve AGA. THMs and their active ingredients achieve enhanced efficacy through interactions with multiple targets, of which NLRP3 is a main therapeutic target. Nonetheless, given the intricate composition of traditional Chinese medicine (TCM), additional research is required to unravel the underlying mechanisms and molecular targets through which THMs alleviate AGA.
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Affiliation(s)
- Siwei Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Wei Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China.
| | - Bowen Wei
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Aihua Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yiwen Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Wen Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Jingyue Gao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yue Jin
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Hang Lu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Yuxiu Ka
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Qingyun Yue
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
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Stamp L, Te Karu L, Reid S, Wright DFB, Frampton C, Tuitaupe VS, Dalbeth N. Easing the way to achieving target serum urate in people with gout: protocol for a non-inferiority randomised strategy trial using an allopurinol dosing model in Aotearoa/New Zealand (the Easy-Allo Study). BMJ Open 2024; 14:e084665. [PMID: 39097306 PMCID: PMC11298718 DOI: 10.1136/bmjopen-2024-084665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 07/19/2024] [Indexed: 08/05/2024] Open
Abstract
INTRODUCTION Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Māori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Māori men and Pacific men, who frequently do not receive optimal care. METHODS AND ANALYSIS A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months. ETHICS AND DISSEMINATION The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants. TRIAL REGISTRATION NUMBER ACTRN12622001279718p.
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Affiliation(s)
- Lisa Stamp
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | - Leanne Te Karu
- Department of General Practice and Primary Health Care, University of Auckland, Auckland, Aotearoa New Zealand
| | - Susan Reid
- Health Literacy NZ, Auckland, New Zealand
| | - Daniel F B Wright
- School of Pharmacy, University of Sydney, Sydney, New South Wales, Australia
| | - Chris Frampton
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | | | - Nicola Dalbeth
- Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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Madanchi M, Young M, Tersalvi G, Maria Cioffi G, Attinger-Toller A, Cuculi F, Kurmann R, Bossard M. The impact of colchicine on patients with acute and chronic coronary artery disease. Eur J Intern Med 2024; 125:1-9. [PMID: 38238134 DOI: 10.1016/j.ejim.2024.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/18/2023] [Accepted: 01/11/2024] [Indexed: 07/04/2024]
Abstract
Inflammation plays a central role in coronary artery disease (CAD), and recent data have shown that anti-inflammatory drugs have the potential to reduce ischemic events in CAD patients. Colchicine is an ancient anti-inflammatory drug that targets neutrophil and inflammasome activities. It has been prescribed for decades for different rheumatological conditions. Given the important role of inflammation in the development of cardiovascular disease, there has been considerable interest in studying colchicine's potential to limit the progression of atherosclerosis among afflicted patients. In fact, there is a growing body of randomized data suggesting that use of low-dose colchicine reduces the risk of ischemic events in patients with CAD, particularly repeated revascularizations, new myocardial infarctions and strokes. This review article summarizes background information-including possible side effects and contraindications-as well as the current evidence backing up the use of colchicine in patients with established CAD.
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Affiliation(s)
- Mehdi Madanchi
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Mabelle Young
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Gregorio Tersalvi
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Giacomo Maria Cioffi
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Adrian Attinger-Toller
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Florim Cuculi
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland
| | - Reto Kurmann
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland; Department of Cardiovascular Diseases, Mayo Clinic Rochester, MN, USA
| | - Matthias Bossard
- Cardiology Division, Heart Center, Luzerner Kantonsspital, Spitalstrasse 16, 6000 Lucerne, Switzerland.
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Dillman KM, Hawkins AM, Ragland AR, Wester GC, Greene DR, Varrassi G, Moore P, Behara R, Ahmadzadeh S, Siddaiah H, Shekoohi S, Kaye AD. Allopurinol: Clinical Considerations in the Development and Treatment of Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, and Other Associated Drug Reactions. Cureus 2024; 16:e64654. [PMID: 39149682 PMCID: PMC11326749 DOI: 10.7759/cureus.64654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 07/15/2024] [Indexed: 08/17/2024] Open
Abstract
Allopurinol lowers urate production through the inhibition of xanthine oxidase. It is oxidatively hydroxylated to oxypurinol and is the most prescribed medication for gout treatment. Although it has a beneficial effect in the treatment of this common disease, like many medications, it is also known for having numerous adverse effects. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), diseases that exist on a spectrum, are two of the most dangerous adverse effects associated with allopurinol use. These immune-mediated disease processes involve almost every organ system. They are essential to recognize as early as possible, as they could potentially be deadly, requiring cessation of the medication with initial signs of rash or other early manifestations of SJS/TEN. One major consideration in the increased risk of allopurinol-mediated or modulated SJS/TEN is the need to have a lower dose in the setting of renal disease. The purpose of this review is not only to examine the involvement of allopurinol in SJS/TEN but also to provide detailed information about the drug, allopurinol, and general features and characteristics of SJS/TEN and other associated drug reactions.
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Affiliation(s)
- Kathryn M Dillman
- Medicine, Louisiana State University Health Sciences Center New Orleans, New Orleans, USA
| | - Alison M Hawkins
- Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Amanda R Ragland
- Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Grace C Wester
- Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Driskell R Greene
- Medicine, Louisiana State University Health Sciences Center, Shreveport, USA
| | | | - Peyton Moore
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Raju Behara
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Shahab Ahmadzadeh
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Harish Siddaiah
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Sahar Shekoohi
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
| | - Alan D Kaye
- Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, USA
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15
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Fan Y, Zhu C, Ji Y, Peng J, Wang G, Wan R, Liu W. Comparison of efficacy of acupuncture-related therapies in treating Acute Gouty Arthritis: A Network Meta-Analysis of Randomized Controlled Trials. Heliyon 2024; 10:e28122. [PMID: 38576580 PMCID: PMC10990962 DOI: 10.1016/j.heliyon.2024.e28122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 03/08/2024] [Accepted: 03/12/2024] [Indexed: 04/06/2024] Open
Abstract
Background and purpose: Acupuncture and moxibustion, as a complementary and alternative therapy, has been widely used in the treatment of acute gouty arthritis (AGA). However, there are various forms of acupuncture and moxibustion, and the curative effect of different forms is different. This study evaluated the clinical efficacy of different acupuncture therapies in treating AGA by network meta-analysis. Methods Computer searches of English databases (including PubMed, The Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Embase) and Chinese databases (including China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang Database and China Biomedical Literature Database) were conducted for randomized controlled trials (RCTs) of acupuncture therapies in treating AGA. We set the search time from the database establishment to May 2022. Data analysis was performed using Stata14.2 software. Results Thirty-two RCTs involving 2434 patients with AGA were screened out. The results showed that in terms of the improvement of pain visual analogue scale (VAS) scores, the top ones were acupoint application (100%), electroacupuncture + Western medicine (73.5%) and acupuncture + Western medicine (69.2%); In terms of total effective rate, acupoint application (85.2%), acupuncture (75.2%) and acupuncture + Western medicine (63%) ranked the top; In terms of reducing serum uric acid (SUA) levels, the top ones were acupoint application (95%), acupuncture + Western medicine (87.5%) and acupuncture (66.2%); In terms of the reduction of erythrocyte sedimentation rate (ESR), acupuncture (95%), acupoint application (84.7%), and electroacupuncture + Western medicine (52.8%) were the most prominent. Conclusion The existing evidence shows that acupoint application has more advantages in improving the total effective rate, improving pain and reduce SUA levels, and acupuncture has an advantage in reducing ESR levels and adverse events. However, due to the low qualities of the original studies, the quality of this evidence is poor. Therefore, it is recommended that more scientific research be performed to confirm the efficacy of acupuncture.
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Affiliation(s)
- Yihua Fan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, China
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
| | - Chengcheng Zhu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, China
| | - Yue Ji
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Jing Peng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, China
| | - Guanran Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
| | - Renhong Wan
- Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, Sichuan Province, China
| | - Wei Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China
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Li YW, Chen SX, Yang Y, Zhang ZH, Zhou WB, Huang YN, Huang ZQ, He JQ, Chen TF, Wang JF, Liu ZY, Chen YX. Colchicine Inhibits NETs and Alleviates Cardiac Remodeling after Acute Myocardial Infarction. Cardiovasc Drugs Ther 2024; 38:31-41. [PMID: 35900652 DOI: 10.1007/s10557-022-07326-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/07/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE Colchicine, a multipotent anti-inflammatory drug, has been reported to alleviate cardiac remodeling and improve cardiac function after acute myocardial infarction (AMI). However, the underlying mechanism remains incompletely understood. Because neutrophils extracellular traps (NETs) enhance inflammation and participate in myocardial ischemia injury, and colchicine can inhibit NETosis, we thus aimed to determine whether colchicine exerts cardioprotective effects on AMI via suppressing NETs. METHODS Adult C57BL/6 mice were subjected to permanent ligation of the left anterior descending coronary artery and treated with colchicine (0.1 mg/kg/day) or Cl-amidine (10 mg/kg/day) for 7 or 28 days after AMI. Cardiac function was evaluated by echocardiography, and NETs detected by immunofluorescence. ROS production was detected using 2',7'-dichlorodihydrofluorescein diacetates (DCFH-DA) fluorometry. Intracellular Ca2+ concentration was assessed by a fluorometric ratio technique. RESULTS We found that colchicine treatment significantly increased mice survival (89.8% in the colchicine group versus 67.9% in control, n = 32 per group; log-rank test, p < 0.05) and improved cardiac function at day 7 (left ventricular ejection fraction (LVEF): 28.0 ± 9.2% versus 12.6 ± 3.9%, n = 8 per group; p < 0.001) and at day 28 (LVEF: 26.2 ± 7.2% versus 14.8 ± 6.7%, n = 8 per group; p < 0.001) post-AMI. In addition, the administration of colchicine inhibited NETs formation and inflammation. Furthermore, colchicine inhibited NETs formation by reducing NOX2/ROS production and Ca2+ influx. Moreover, prevention of NETs formation with Cl-amidine significantly alleviated AMI-induced cardiac remodeling. CONCLUSIONS Colchicine inhibited NETs and cardiac inflammation, and alleviated cardiac remodeling after acute myocardial infarction.
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Affiliation(s)
- Yue-Wei Li
- Department of Respiratory Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Si-Xu Chen
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ying Yang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zeng-Hui Zhang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wei-Bin Zhou
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yu-Na Huang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Zhao-Qi Huang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jia-Qi He
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Ting-Feng Chen
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jing-Feng Wang
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China.
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China.
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Zhao-Yu Liu
- Medical Research Center, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
| | - Yang-Xin Chen
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510120, China.
- Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province, Guangzhou, China.
- Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
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Sivasegaran S, Hanafi NSH. Perceptions and practices of self-management among adult patients with gout at a primary care clinic: A qualitative study. MALAYSIAN FAMILY PHYSICIAN : THE OFFICIAL JOURNAL OF THE ACADEMY OF FAMILY PHYSICIANS OF MALAYSIA 2023; 18:72. [PMID: 38213387 PMCID: PMC10781610 DOI: 10.51866/oa.428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Introduction Gout is a chronic disease commonly associated with other comorbidities. Patients' perceived quality of life empowers them in managing their health. Self-management is imparted as part of management among patients with chronic disease. This study aimed to explore the perceptions and practices of self-management among patients with gout from different ethnic groups in Malaysia. Methods A qualitative study was conducted among Malay, Chinese and Indian patients with gout via semi-structured in-depth interviews at the primary care clinic of University Malaya Medical Centre in either English or Malay language. All participants had a gout duration of more than 6 months and were either taking urate-lowering drugs or not using them at all. Results A total of 20 participants were successfully recruited for the study. Among the participants, 18 were men, while two were women. Further, nine were Malays; six, Chinese; and four, Indians. The age ranged from 29 to 81 years, while the gout duration ranged from 1 to 30 years. From the interviews, three themes emerged: experiences with gout, types of self-management of gout and factors influencing self-management of gout. Conclusion Diet control is the main self-management practice of patients with gout. Traditional medicine practices include natural methods such as consumption of different types of vegetable juices, pineapple and papaya. Each ethnicity has its own unique beliefs and food cultures. By understanding the self-management practices of patients from diverse ethnic backgrounds, healthcare practitioners can tailor the treatment of gout to individual needs.
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Affiliation(s)
- Suhashini Sivasegaran
- MD, MMed, Klinik Kesihatan Sandakan, K.M 3.2, Jln Utara Beg Berkunci No. 4, Sandakan, Sabah, Malaysia.
| | - Nik Sherina Haidi Hanafi
- MBBS, MFamMed, PhD, Department of Primary Care Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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18
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Stamp L, Horne A, Mihov B, Drake J, Haslett J, Chapman PT, Frampton C, Dalbeth N. Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. Ann Rheum Dis 2023; 82:1626-1634. [PMID: 37652661 DOI: 10.1136/ard-2023-224731] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 08/18/2023] [Indexed: 09/02/2023]
Abstract
OBJECTIVES To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the 'start-low go-slow' dose approach. METHODS A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months. RESULTS Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo. CONCLUSIONS Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the 'start-low go-slow' strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period. TRIAL REGISTRATION NUMBER ACTRN 12618001179224.
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Affiliation(s)
- Lisa Stamp
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | - Anne Horne
- Department of Medicine, The Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Borislav Mihov
- Department of Medicine, The Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Jill Drake
- Department of Rheumatology, Immunology and Allergy, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Janine Haslett
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | - Peter T Chapman
- Department of Rheumatology, Immunology and Allergy, Te Whatu Ora Health New Zealand Waitaha Canterbury, Christchurch, New Zealand
| | - Christopher Frampton
- Department of Medicine, University of Otago, Christchurch, Christchurch, New Zealand
| | - Nicola Dalbeth
- Department of Medicine, The Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
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19
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Riaz M, Jha S. Syracuse Hemoglobinopathy Presenting With Tophaceous Gout: A Case Report. Fed Pract 2023; 40:358-360. [PMID: 38567297 PMCID: PMC10984683 DOI: 10.12788/fp.0419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Abstract
Background Hemoglobinopathies are inherited disorders of hemoglobin that alter oxygen binding capacity by affecting the production of a specific subset of globin chains or their entire structure. A lesser-known subtype, Syracuse hemoglobinopathy, was first identified in 4 generations of a family in the 1970s. Gout has been reported in several forms of hemoglobinopathy, such as thalassemia and hemoglobin C disorder. Case Presentation A 44-year-old man with a known history of Syracuse hemoglobinopathy, tobacco use disorder, and shoulder osteoarthritis presented with diffuse nodular masses on his joints along with joint pain. His laboratory tests and imaging showed elevated uric acid, urate crystals in his synovial fluid, and bony erosions. These findings were concerning for gout, which was treated with allopurinol, prednisone, and colchicine, resulting in improvement in his symptoms. Conclusions Syracuse hemoglobinopathy, a rare disorder of high oxygen affinity hemoglobin, can present itself with findings of elevated serum uric acid and tophaceous gout. Most patients with hyperuricemia never go on to develop gout. However, having a condition that increases serum levels of uric acid should raise an astute clinician's suspicion when a patient presents with a history of hemoglobinopathy and joint pain.
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Affiliation(s)
| | - Swastika Jha
- Central Texas Veterans Affairs Health Care System, Temple
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20
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So MW, Kim AR, Lee SG. Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database. Int J Rheum Dis 2023; 26:1770-1778. [PMID: 37431263 DOI: 10.1111/1756-185x.14825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/12/2023]
Abstract
INTRODUCTION We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. METHODS Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. RESULTS This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). CONCLUSION Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.
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Affiliation(s)
- Min Wook So
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea
- Division of Rheumatology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - A-Ran Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea
- Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Seung-Geun Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea
- Division of Rheumatology, Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea
- Biomedical Research Institute, Pusan National University Hospital, Busan, South Korea
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21
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Botson JK, Saag K, Peterson J, Obermeyer K, Xin Y, LaMoreaux B, Padnick‐Silver L, Verma S, Grewal S, Majjhoo A, Tesser JRP, Weinblatt ME. A Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients With Uncontrolled Gout Receiving Pegloticase: 12-Month Findings. ACR Open Rheumatol 2023; 5:407-418. [PMID: 37385296 PMCID: PMC10425585 DOI: 10.1002/acr2.11578] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/08/2023] [Accepted: 05/22/2023] [Indexed: 07/01/2023] Open
Abstract
OBJECTIVE To assess 12-month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO-controlled, double-blind trial (A randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRROR RCT]). METHODS Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8-mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent-to-treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU-monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. RESULTS Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%-44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%-44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. CONCLUSION Twelve-month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect.
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Affiliation(s)
| | | | | | | | - Yan Xin
- Horizon Therapeutics plcDeerfieldIllinois
| | | | | | | | - Suneet Grewal
- East Bay Rheumatology Medical Group Inc.San LeandroCalifornia
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22
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Wong PKK, Ng BCK, Mitchell J, Han J, Lam C, Spencer D, Cai K, Manolios N. The disproportionately large contribution of the Māori and Pacific Islander community to the healthcare burden of gout in Western Sydney. Intern Med J 2023; 53:1450-1457. [PMID: 35670212 DOI: 10.1111/imj.15831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/24/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Gout is a common chronic inflammatory disorder due to monosodium urate deposition, which results in severe inflammatory arthritis. It is particularly common in those of Māori or Pacific Islander heritage. There is a significant number of this at-risk ethnic group in western Sydney. AIMS To determine the healthcare burden of gout in Western Sydney. METHODS We characterised patients managed in the emergency departments (EDs) of the four Western Sydney Local Health District (WSLHD) hospitals and those admitted for gout as the primary or secondary diagnosis from 1 January 2017 to 31 December 2018. RESULTS There were 472 patients managed in ED on 552 occasions at a direct cost to the LHD of A$367 835. Those of Māori or Pacific Islander ethnicity comprised 25.2% (n = 119/472), while half (n = 39/80) of those managed in ED for gout on two or more occasions were of Māori or Pacific Islander ethnicity. Overall, 310 patients were admitted with gout as the principal diagnosis on 413 occasions at a cost of A$1.73 million. Seventy-five (24.2%) of the 310 patients were of Māori or Pacific Islander heritage. A total of 584 WSLHD inpatients had gout as a secondary diagnosis. This was associated with 714 admissions. CONCLUSIONS The disproportionately large healthcare burden of gout in Western Sydney from the relatively small Māori and Pacific Islander population needs attention. Urgent culturally appropriate interventions to address gout are required to address this inequality.
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Affiliation(s)
- Peter K K Wong
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
- Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia
- The University of New South Wales Rural Clinical School, Coffs Harbour, New South Wales, Australia
| | - Beverly C K Ng
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
| | - James Mitchell
- Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia
| | - Joanne Han
- Clinical Analytics Unit, Western Sydney Local Health District, Sydney, New South Wales, Australia
| | - Cinda Lam
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
| | - David Spencer
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
- Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia
| | - Ken Cai
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
- Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia
| | - Nicholas Manolios
- Department of Rheumatology, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, Australia
- Westmead Clinical School, Faculty of Medicine and Health Sciences, The University of Sydney, Sydney, New South Wales, Australia
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23
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Maghsoud Y, Dong C, Cisneros GA. Investigation of the Inhibition Mechanism of Xanthine Oxidoreductase by Oxipurinol: A Computational Study. J Chem Inf Model 2023; 63:4190-4206. [PMID: 37319436 PMCID: PMC10405278 DOI: 10.1021/acs.jcim.3c00624] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Xanthine oxidoreductase (XOR) is an enzyme found in various organisms. It converts hypoxanthine to xanthine and urate, which are crucial steps in purine elimination in humans. Elevated uric acid levels can lead to conditions like gout and hyperuricemia. Therefore, there is significant interest in developing drugs that target XOR for treating these conditions and other diseases. Oxipurinol, an analogue of xanthine, is a well-known inhibitor of XOR. Crystallographic studies have revealed that oxipurinol directly binds to the molybdenum cofactor (MoCo) in XOR. However, the precise details of the inhibition mechanism are still unclear, which would be valuable for designing more effective drugs with similar inhibitory functions. In this study, molecular dynamics and quantum mechanics/molecular mechanics calculations are employed to investigate the inhibition mechanism of XOR by oxipurinol. The study examines the structural and dynamic effects of oxipurinol on the pre-catalytic structure of the metabolite-bound system. Our results provide insights on the reaction mechanism catalyzed by the MoCo center in the active site, which aligns well with experimental findings. Furthermore, the results provide insights into the residues surrounding the active site and propose an alternative mechanism for developing alternative covalent inhibitors.
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Affiliation(s)
- Yazdan Maghsoud
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Chao Dong
- Department of Chemistry and Physics, The University of Texas Permian Basin, Odessa, Texas 79762, United States
| | - G Andrés Cisneros
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
- Department of Physics, The University of Texas at Dallas, Richardson, Texas 75080, United States
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24
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Maghsoud Y, Dong C, Cisneros GA. Computational Characterization of the Inhibition Mechanism of Xanthine Oxidoreductase by Topiroxostat. ACS Catal 2023; 13:6023-6043. [PMID: 37547543 PMCID: PMC10399974 DOI: 10.1021/acscatal.3c01245] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/08/2023]
Abstract
Xanthine oxidase (XO) is a member of the molybdopterin-containing enzyme family. It interconverts xanthine to uric acid as the last step of purine catabolism in the human body. The high uric acid concentration in the blood directly leads to human diseases like gout and hyperuricemia. Therefore, drugs that inhibit the biosynthesis of uric acid by human XO have been clinically used for many years to decrease the concentration of uric acid in the blood. In this study, the inhibition mechanism of XO and a new promising drug, topiroxostat (code: FYX-051), is investigated by employing molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. This drug has been reported to act as both a noncovalent and covalent inhibitor and undergoes a stepwise inhibition by all its hydroxylated metabolites, which include 2-hydroxy-FYX-051, dihydroxy-FYX-051, and trihydroxy-FYX-051. However, the detailed mechanism of inhibition of each metabolite remains elusive and can be useful for designing more effective drugs with similar inhibition functions. Hence, herein we present the computational investigation of the structural and dynamical effects of FYX-051 and the calculated reaction mechanism for all of the oxidation steps catalyzed by the molybdopterin center in the active site. Calculated results for the proposed reaction mechanisms for each metabolite's inhibition reaction in the enzyme's active site, binding affinities, and the noncovalent interactions with the surrounding amino acid residues are consistent with previously reported experimental findings. Analysis of the noncovalent interactions via energy decomposition analysis (EDA) and noncovalent interaction (NCI) techniques suggests that residues L648, K771, E802, R839, L873, R880, R912, F914, F1009, L1014, and A1079 can be used as key interacting residues for further hybrid-type inhibitor development.
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Affiliation(s)
- Yazdan Maghsoud
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States
| | - Chao Dong
- Department of Chemistry and Physics, The University of Texas Permian Basin, Odessa, Texas 79762, United States
| | - G Andrés Cisneros
- Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, Texas 75080, United States; Department of Physics, The University of Texas at Dallas, Richardson, Texas 75080, United States
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25
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Ashimi MHBN, Taib WRW, Ismail I, Mutalib NSA, Rahim SM. The regulatory role of miRNA towards expressed genes in the pathogenesis of gout: A review. HUMAN GENE 2023; 36:201163. [DOI: 10.1016/j.humgen.2023.201163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Yip RM, Cheung TT, So H, Chan JP, Ho CT, Tsang HH, Yu CK, Wong PC. The Hong Kong Society of Rheumatology consensus recommendations for the management of gout. Clin Rheumatol 2023:10.1007/s10067-023-06578-9. [PMID: 37014501 DOI: 10.1007/s10067-023-06578-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 02/09/2023] [Accepted: 03/12/2023] [Indexed: 04/05/2023]
Abstract
Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains suboptimal. Like other countries, the treatment goal in Hong Kong usually focuses on relieving symptoms of gout but not treating the serum urate level to target. As a result, patients with gout continue to suffer from the debilitating arthritis, as well as the renal, metabolic, and cardiovascular complications associated with gout. The Hong Kong Society of Rheumatology spearheaded the development of these consensus recommendations through a Delphi exercise that involved rheumatologists, primary care physicians, and other specialists in Hong Kong. Recommendations on acute gout management, gout prophylaxis, treatment of hyperuricemia and its precautions, co-administration of non-gout medications with urate-lowering therapy, and lifestyle advice have been included. This paper serves as a reference guide to all healthcare providers who see patients who are at risk and are known to have this chronic but treatable condition.
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Affiliation(s)
- Ronald Ml Yip
- Tung Wah Group of Hospitals Integrated Diagnostic and Medical Centre, Kwong Wah Hospital, 25, Waterloo Road, Kowloon, Hong Kong.
| | - Tommy T Cheung
- Rheumatology Centre, Department of Medicine, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong
| | - Ho So
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
| | - Julia Ps Chan
- Rheumatology Centre, Department of Medicine, Hong Kong Sanatorium & Hospital, Happy Valley, Hong Kong
| | - Carmen Tk Ho
- Division of Rheumatology and Clinical Immunology, Queen Mary Hospital, Pok Fu Lam, Hong Kong
| | - Helen Hl Tsang
- Division of Rheumatology and Clinical Immunology, Queen Mary Hospital, Pok Fu Lam, Hong Kong
| | - Carrel Kl Yu
- Hong Kong Autoimmune and Rheumatic Diseases Centre, Central, Hong Kong
| | - Priscilla Ch Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Ma Liu Shui, Hong Kong
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Neoisoastilbin Ameliorates Acute Gouty Arthritis via Suppression of the NF- κB/NLRP3 Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2023; 2023:7629066. [PMID: 36824696 PMCID: PMC9943619 DOI: 10.1155/2023/7629066] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/16/2023] [Accepted: 02/01/2023] [Indexed: 02/16/2023]
Abstract
Acute gouty arthritis (AGA) is an acute inflammatory disease, whose occurrence and development mechanism are associated with inflammatory reaction of joint tissue. This study investigated the role of neoisoastilbin (NIA) in the treatment of AGA and explored the underlying mechanisms. C57BL/6 mice underwent intraarticular injection of monosodium urate (MSU) to establish an AGA model in vivo. Enzyme-linked immunosorbent assay, histopathological hematoxylin-eosin staining, western blotting, and other methods were used to observe the therapeutic effects of NIA on AGA and investigate the role of the NF-κB/NLRP3 pathway in the treatment. We found that NIA effectively reduced MSU-induced joint swelling and inflammatory cell infiltration in a concentration-dependent manner. NIA also significantly reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels as compared with the respective values in the model mice group. In addition, administration of NIA significantly mitigated the phosphorylation of NF-κB-related proteins (IKKα, NF-κB, and IκBα) and the expression of NLRP3-related proteins (NLRP3, caspase-1, and ASC) in MSU-induced joint tissues. In conclusion, our research indicated that NIA significantly improved AGA, and its underlying mechanism was achieved by simultaneously inhibiting the NF-κB/NLRP3 pathway and the expression of inflammatory factors. This research preliminarily suggested the potential role of NIA in the treatment of AGA.
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Botson JK, Saag K, Peterson J, Parikh N, Ong S, La D, LoCicero K, Obermeyer K, Xin Y, Chamberlain J, LaMoreaux B, Verma S, Sainati S, Grewal S, Majjhoo A, Tesser JRP, Weinblatt ME. A Randomized, Placebo-Controlled Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled Gout Receiving Pegloticase: Primary Efficacy and Safety Findings. Arthritis Rheumatol 2023; 75:293-304. [PMID: 36099211 PMCID: PMC10107774 DOI: 10.1002/art.42335] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 08/09/2022] [Accepted: 08/19/2022] [Indexed: 02/02/2023]
Abstract
OBJECTIVE To assess efficacy, safety, pharmacokinetics, and immunogenicity of pegloticase plus methotrexate (MTX) versus pegloticase plus placebo cotreatment for uncontrolled gout in a randomized, placebo-controlled, double-blind trial. METHODS This study included adults with uncontrolled gout, defined as serum urate ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of ongoing gout symptoms including ≥1 tophus, ≥2 flares in the past 12 months, or gouty arthritis. Key exclusion criteria included MTX contraindication, current immunosuppressant use, G6PDH deficiency, and estimated glomerular filtration rate <40 ml/minute/1.73 m2 . Patients were randomized 2:1 to 52 weeks of pegloticase (8 mg biweekly) with either oral MTX (15 mg/week) or placebo. The primary end point was the proportion of treatment responders during month 6 (defined as serum urate <6 mg/dl for ≥80% of visits during weeks 20-24). Efficacy was evaluated in all randomized patients (intent-to-treat population), and safety was evaluated in all patients receiving ≥1 blinded MTX or placebo dose. RESULTS A total of 152 patients were randomized, 100 to receive pegloticase plus MTX, 52 to receive pegloticase plus placebo. Significantly higher treatment response occurred during month 6 in the MTX group versus the placebo group (71.0% [71 of 100 patients] versus 38.5% [20 of 52 patients], respectively; between-group difference 32.3% [95% confidence interval 16.3%, 48.3%]) (P < 0.0001 for between-group difference). During the first 6 months of pegloticase plus MTX or pegloticase plus placebo treatment, 78 (81.3%) of 96 MTX patients versus 47 (95.9%) of 49 placebo patients experienced ≥1 adverse event (AE), most commonly gout flare (64 [66.7%] of 96 MTX patients and 34 [69.4%] of 49 placebo patients). Reports of AEs and serious AEs were comparable between groups, but the infusion reaction rate was considerably lower with MTX cotherapy (4.2% [4 of 96 MTX patients, including 1 patient who had anaphylaxis]) than with placebo cotherapy (30.6% [15 of 49 placebo patients, 0 who had anaphylaxis]) (P < 0.001). Antidrug antibody positivity was also lower in the MTX group. CONCLUSION MTX cotherapy markedly increased pegloticase response rate over placebo (71.0% versus 38.5%) during month 6 with no new safety signals. These findings verify higher treatment response rate, lower infusion reaction incidence, and lower immunogenicity when pegloticase is coadministered with MTX.
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Affiliation(s)
| | | | - Jeff Peterson
- Western Washington Arthritis Clinic, Bothell, Washington
| | | | | | - Dan La
- Keck USC Medical Center, Los Angeles, California
| | | | | | - Yan Xin
- Horizon Therapeutics plc, Deerfield, Illinois
| | | | | | - Supra Verma
- Horizon Therapeutics plc, Deerfield, Illinois
| | | | - Suneet Grewal
- East Bay Rheumatology Medical Group Inc., San Leandro, California
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Wen YF, Culhane-Pera KA, Pergament SL, Moua Y, Vue B, Yang T, Lo M, Sun B, Knights D, Straka RJ. Hmong microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C): A phase II clinical study protocol. PLoS One 2023; 18:e0279830. [PMID: 36724193 PMCID: PMC9891498 DOI: 10.1371/journal.pone.0279830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 11/29/2022] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Hmong men in Minnesota exhibit a high prevalence of gout and hyperuricemia. Although evidence of vitamin C's effectiveness as a treatment for gout is mixed, analysis of therapeutic benefit based on an individual's multiomic signature may identify predictive markers of treatment success. OBJECTIVES The primary objective of the Hmong Microbiome ANd Gout, Obesity, Vitamin C (HMANGO-C) study was to assess the effectiveness of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The secondary objectives were to assess if 1) vitamin C impacts the taxonomic and functional patterns of microbiota; 2) taxonomic and functional patterns of microbiota impact vitamin C's urate-lowering effects; 3) genetic variations impact vitamin C's urate-lowering effects; 4) differential microbial biomarkers exist for patients with or without gout; and 5) there is an association between obesity, gut microbiota and gout/hyperuricemia. METHODS This prospective open-labelled clinical trial was guided by community-based participatory research principles and conducted under research safety restrictions for SARS-CoV-2. We aimed to enroll a convenient sample of 180 Hmong adults (120 with gout/hyperuricemia and 60 without gout/hyperuricemia) who provided medical, demographic, dietary and anthropometric information. Participants took vitamin C 500mg twice daily for 8 weeks and provided pre-and post- samples of blood and urine for urate measurements as well as stool samples for gut microbiome. Salivary DNA was also collected for genetic markers relevant to uric acid disposition. EXPECTED RESULTS We expected to quantify the impact of vitamin C on serum urate in Hmong adults with and without gout/hyperuricemia. The outcome will enhance our understanding of how gut microbiome and genomic variants impact the urate-lowering of vitamin C and associations between obesity, gut microbiota and gout/hyperuricemia. Ultimately, findings may improve our understanding of the causes and potential interventions that could be used to address health disparities in the prevalence and management of gout in this underserved population. TRIAL REGISTRATION ClinicalTrials.gov NCT04938024 (first posted: 06/24/2021).
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Affiliation(s)
- Ya-Feng Wen
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Kathleen A. Culhane-Pera
- Minnesota Community Care, St. Paul, Minnesota, United States of America
- SoLaHmo Partnership for Health and Wellness, Community-University Health Care Center, Minneapolis, Minnesota, United States of America
| | - Shannon L. Pergament
- SoLaHmo Partnership for Health and Wellness, Community-University Health Care Center, Minneapolis, Minnesota, United States of America
| | - Yeng Moua
- SoLaHmo Partnership for Health and Wellness, Community-University Health Care Center, Minneapolis, Minnesota, United States of America
| | - Bai Vue
- SoLaHmo Partnership for Health and Wellness, Community-University Health Care Center, Minneapolis, Minnesota, United States of America
| | - Toua Yang
- SoLaHmo Partnership for Health and Wellness, Community-University Health Care Center, Minneapolis, Minnesota, United States of America
| | - Muaj Lo
- Minnesota Community Care, St. Paul, Minnesota, United States of America
| | - Boguang Sun
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Dan Knights
- Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, Minnesota, United States of America
- Biotechnology Institute, University of Minnesota, Minneapolis, Minnesota, United States of America
- Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Robert J. Straka
- Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, United States of America
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Kong X, Liang H, An W, Bai S, Miao Y, Qiang J, Wang H, Zhou Y, Zhang Q. Rapid identification of early renal damage in asymptomatic hyperuricemia patients based on urine Raman spectroscopy and bioinformatics analysis. Front Chem 2023; 11:1045697. [PMID: 36762194 PMCID: PMC9905717 DOI: 10.3389/fchem.2023.1045697] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/16/2023] [Indexed: 01/26/2023] Open
Abstract
Objective: The issue of when to start treatment in patients with hyperuricemia (HUA) without gout and chronic kidney disease (CKD) is both important and controversial. In this study, Raman spectroscopy (RS) was used to analyze urine samples, and key genes expressed differentially CKD were identified using bioinformatics. The biological functions and regulatory pathways of these key genes were preliminarily analyzed, and the relationship between them as well as the heterogeneity of the urine components of HUA was evaluated. This study provides new ideas for the rapid evaluation of renal function in patients with HUA and CKD, while providing an important reference for the new treatment strategy of HUA disease. Methods: A physically examined population in 2021 was recruited as the research subjects. There were 10 cases with normal blood uric acid level and 31 cases with asymptomatic HUA diagnosis. The general clinical data were collected and the urine samples were analyzed by Raman spectroscopy. An identification model was also established by using the multidimensional multivariate method of orthogonal partial least squares discriminant analysis (OPLS-DA) model for statistical analysis of the data, key genes associated with CKD were identified using the Gene Expression Omnibus (GEO) database, and key biological pathways associated with renal function damage in CKD patients with HUA were analyzed. Results: The Raman spectra showed significant differences in the levels of uric acid (640 cm-1), urea, creatinine (1,608, 1,706 cm-1), proteins/amino acids (642, 828, 1,556, 1,585, 1,587, 1,596, 1,603, 1,615 cm-1), and ketone body (1,643 cm-1) (p < 0.05). The top 10 differentially expressed genes (DEGs) associated with CKD (ALB, MYC, IL10, FOS, TOP2A, PLG, REN, FGA, CCNA2, and BUB1) were identified. Compared with the differential peak positions analyzed by the OPLS-DA model, it was found that the peak positions of glutathione, tryptophan and tyrosine may be important markers for the diagnosis and progression of CKD. Conclusion: The progression of CKD was related to the expression of the ALB, MYC, IL10, PLG, REN, and FGA genes. Patients with HUA may have abnormalities in glutathione, tryptophan, tyrosine, and energy metabolism. The application of Raman spectroscopy to analyze urine samples and interpret the heterogeneity of the internal environment of asymptomatic HUA patients can be combined with the OPLS-DA model to mine the massive clinical and biochemical examination information on HUA patients. The results can also provide a reference for identifying the right time for intervention for uric acid as well as assist the early detection of changes in the internal environment of the body. Finally, this approach provides a useful technical supplement for exploring a low-cost, rapid evaluation and improving the timeliness of screening. Precise intervention of abnormal signal levels of internal environment and energy metabolism may be a potential way to delay renal injury in patients with HUA.
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Affiliation(s)
- Xiaodong Kong
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Haoyue Liang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Wei An
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Sheng Bai
- Department of Ultrasound, Xiangya Hospital Central South University, Changsha, Hunan, China
| | | | - Junlian Qiang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China
| | - Haoyu Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Yuan Zhou
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China,*Correspondence: Qiang Zhang, ; Yuan Zhou,
| | - Qiang Zhang
- Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin Geriatrics Institute, Tianjin, China,*Correspondence: Qiang Zhang, ; Yuan Zhou,
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Verstappen G, Michel O, Halewyck S, Topsakal V, Pössneck A. Infected nasal gout tophus: A case report. Clin Case Rep 2022; 10:e6695. [PMID: 36518917 PMCID: PMC9743314 DOI: 10.1002/ccr3.6695] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/14/2022] [Accepted: 11/18/2022] [Indexed: 12/14/2022] Open
Abstract
Gout is a common form of inflammatory arthritis, characterized by the deposition of monosodium urate crystals. If chronically present and not adequately treated by serum urate reducers, gout tophi can develop at various locations. Here, we report the first infected gout tophus at the septal cartilage and nasal tip.
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Affiliation(s)
- Gill Verstappen
- Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium
| | - Olaf Michel
- Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium
| | - Stijn Halewyck
- Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium
| | - Vedat Topsakal
- Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium
| | - Antje Pössneck
- Department of Otorhinolaryngology - Head and Neck Surgery Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel Brussels Belgium
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Nguyen AD, Lind KE, Day RO, Ross D, Raban MZ, Georgiou A, Westbrook JI. Measuring quality of gout management in residential aged care facilities. Rheumatol Adv Pract 2022; 6:rkac091. [PMID: 36465481 PMCID: PMC9710438 DOI: 10.1093/rap/rkac091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 10/14/2022] [Indexed: 03/30/2025] Open
Abstract
OBJECTIVE Gout, a common form of arthritis, can be controlled successfully with pharmacotherapy and is thus an ideal model for examining chronic disease management. Our aim was to examine treatment of gout evaluated in accordance with general management guidelines for gout as applied to Australian residential aged care facilities. METHODS Electronic health record data linked with aged care clinical notes and electronic medication administration information (11 548 residents in 68 residential aged care facilities, >65 years of age) were interrogated to identify people with gout, other chronic conditions and gout medication use. The outcomes examined were the proportion receiving urate-lowering therapy (ULT; preventative medication) and/or colchicine/non-steroidal anti-inflammatory drug (NSAID) (to treat gout flares), the number of ULT and colchicine/NSAID treatment episodes (periods of continuous days of medication use) and the duration of these treatment episodes. RESULTS The cohort included 1179 residents with gout, of whom 62% used a ULT, with a median of one episode of use for a very short duration [median = 4 days, median of use in total (i.e. repeated use) = 52 days]. Among residents with gout, 9% also used colchicine or an NSAID. Female residents were less likely to receive ULT and for shorter periods. CONCLUSION Nearly one-third of residents with gout did not receive ULT. In those receiving ULT, recurrent short courses were common. Overall, management of gout in aged care residents appears to be suboptimal, largely owing to intermittent and short exposure to ULT, and with female residents at greater risk of poor gout management.
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Affiliation(s)
- Amy D Nguyen
- Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia
- St Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, Sydney, NSW, Australia
| | - Kimberly E Lind
- Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia
| | - Richard O Day
- St Vincent’s Clinical School, UNSW Medicine, UNSW Sydney, Sydney, NSW, Australia
- Department of Clinical Pharmacology & Toxicology, St Vincent’s Hospital, Sydney, NSW, Australia
| | - Daniel Ross
- Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia
| | - Magdalena Z Raban
- Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia
| | - Andrew Georgiou
- Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia
| | - Johanna I Westbrook
- Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia
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Shu C, Yang F, Zhu F, Hua D. Effect of external use of Qingluo San on clinical efficacy in patients with acute gouty arthritis. Eur J Med Res 2022; 27:245. [DOI: 10.1186/s40001-022-00872-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 10/18/2022] [Indexed: 11/13/2022] Open
Abstract
Abstract
Objective
The present study aimed to observe the clinical efficacy of the external use of Qingluo San combined with diclofenac sodium double-release enteric capsules in the treatment of acute gouty arthritis (dampness–heat accumulation syndrome).
Methods
A total of 58 acute gouty arthritis patients were divided into two groups using the random number table method. Diclofenac sodium double-release enteric capsules were orally administered in the control group. Based on the treatment in the control group, the external use of Qingluo San was given in the treatment group, with 7-day course of treatment. The changes in visual analog scale (VAS) scores, the tenderness, swelling, and mobility function of the joint, and the traditional Chinese medicine (TCM) syndrome scores before and after the treatment, at day 0, 1, 3, 5 and 7, were observed in both groups, together with the comparison of laboratory indicators (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; uric acid, UA).
Results
The total effective rate was 96.55% in the treatment group and 82.76% in the control group. After treatment, the VAS score, the tenderness, swelling and function scores of the joint, and the TCM syndrome scores decreased in both groups. The treatment group was superior in improving the VAS scores, the tenderness, swelling and mobility function of the joint, and TCM syndrome scores, when compared to the control group (p < 0.05). The laboratory indicators, which included the ESR, CRP and UA, obviously decreased in both groups after treatment (p < 0.05). The ESR significantly decreased in the treatment group, when compared to the control group (p < 0.05).
Conclusion
The combination of the external use of Qingluo San and oral administration of diclofenac sodium double-release enteric capsules can more rapidly relieve joint pain, and improve the clinical efficacy. This combination therapy also has certain advantages in relieving joint swelling and improving the mobility function of the joint. Hence, this is worthy of clinical promotion and application.
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Hu S, Terkeltaub R, Sun M, Ji X, Li Z, Ran Z, Li Y, Zhang H, Sun W, Li C, Lu J. Palpable tophi and more comorbidities associated with adherence to urate-lowering medical therapy in a Chinese gout cohort. Joint Bone Spine 2022; 89:105435. [PMID: 35777552 DOI: 10.1016/j.jbspin.2022.105435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 06/13/2022] [Accepted: 06/15/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVE Urate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort. METHODS We studied 903 Chinese gout patients aged 46.4±14.7 years (mean±SD), uniquely extending to assay of 2-year medication possession ratio (MPR) ≥80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment. RESULTS Characterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR ≥80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P <0.001), lower flare frequency and palpable tophi compared to MPR <80%. However, only 44.7% of cohort subjects had MPR ≥80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU <6mg/dL (360μmol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85). CONCLUSION Despite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target.
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Affiliation(s)
- Shuhui Hu
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Institute of Metabolic Diseases, Qingdao University, 266003 Qingdao, China
| | - Robert Terkeltaub
- VA San Diego VA Healthcare Center, University of California San Diego, 92093 San Diego, USA
| | - Mingshu Sun
- Department of Rheumatology, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Xiaopeng Ji
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Zhiyuan Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Zijing Ran
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Yushuang Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Hui Zhang
- Institute of Metabolic Diseases, Qingdao University, 266003 Qingdao, China
| | - Wenyan Sun
- Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China
| | - Changgui Li
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Institute of Metabolic Diseases, Qingdao University, 266003 Qingdao, China
| | - Jie Lu
- Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Shandong Provincial Clinical Research Center for Immune Diseases and Gout, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, 266003 Qingdao, China; Institute of Metabolic Diseases, Qingdao University, 266003 Qingdao, China.
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Lu L, Liu T, Liu X, Wang C. Screening and identification of purine degrading Lactobacillus fermentum 9-4 from Chinese fermented rice-flour noodles. FOOD SCIENCE AND HUMAN WELLNESS 2022. [DOI: 10.1016/j.fshw.2022.04.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Cao JF, Xingyu Yang, Li Xiong, Wu M, Chen S, Xu H, Gong Y, Zhang L, Zhang Q, Zhang X. Exploring the mechanism of action of dapansutrile in the treatment of gouty arthritis based on molecular docking and molecular dynamics. Front Physiol 2022; 13:990469. [PMID: 36105284 PMCID: PMC9465377 DOI: 10.3389/fphys.2022.990469] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 08/12/2022] [Indexed: 01/02/2023] Open
Abstract
Purpose: Dapansutrile is an orally active β-sulfonyl nitrile compound that selectively inhibits the NLRP3 inflammasome. Clinical studies have shown that dapansutrile is active in vivo and limits the severity of endotoxin-induced inflammation and joint arthritis. However, there is currently a lack of more in-depth research on the effect of dapansutrile on protein targets such as NLRP3 in gouty arthritis. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of dapansutrile on NLRP3 and other related protein targets. Methods: We use bioinformatics to screen active pharmaceutical ingredients and potential disease targets. The disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were utilized to verify and analyze the binding stability of small molecule drugs to target proteins. The supercomputer platform was used to measure and analyze the binding free energy, the number of hydrogen bonds, the stability of the protein target at the residue level, the radius of gyration and the solvent accessible surface area. Results: The protein interaction network screened out the core protein targets (such as: NLRP3, TNF, IL1B) of gouty arthritis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that gouty arthritis mainly played a vital role by the signaling pathways of inflammation and immune response. Molecular docking showed that dapansutrile play a role in treating gouty arthritis by acting on the related protein targets such as NLRP3, IL1B, IL6, etc. Molecular dynamics was used to prove and analyze the binding stability of active ingredients and protein targets, the simulation results found that dapansutrile forms a very stable complex with IL1B. Conclusion: We used bioinformatics analysis and computer simulation system to comprehensively explore the mechanism of dapansutrile acting on NLRP3 and other protein targets in gouty arthritis. This study found that dapansutrile may not only directly inhibit NLRP3 to reduce the inflammatory response and pyroptosis, but also hinder the chemotaxis and activation of inflammatory cells by regulating IL1B, IL6, IL17A, IL18, MMP3, CXCL8, and TNF. Therefore, dapansutrile treats gouty arthritis by attenuating inflammatory response, inflammatory cell chemotaxis and extracellular matrix degradation by acting on multiple targets.
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Educate and treat to eliminate gout flares in elderly patients. DRUGS & THERAPY PERSPECTIVES 2022. [DOI: 10.1007/s40267-022-00934-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Abstract
The range of drug treatment options to treat acute and chronic gout has changed dramatically over the last 20 years. Yet, there is general consensus that drug therapy selection, dosing and dose titration, of both traditional and novel agents is far from optimally delivered in clinical practice. Updated guidelines disseminated in the last 5 years, from the American College of Physicians, the European League Against Rheumatism, and the American College of Rheumatology, provide clear guidance to the medical community on how and when to optimally integrate these therapeutic options into practice to improve the medical management of gout.
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Affiliation(s)
- Allan C Gelber
- Johns Hopkins University School of Medicine, Mason F. Lord Building, Center Tower, Suite 4100, 5200 Eastern Avenue, Baltimore, MD 21224, USA.
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Mikdashi J. The Meaningful Role of Patients, and Other Stakeholders in Clinical Practice Guideline Development. Rheum Dis Clin North Am 2022; 48:691-703. [DOI: 10.1016/j.rdc.2022.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Deng P, Wang S, Sun X, Qi Y, Ma Z, Pan X, Liang H, Wu J, Chen Z. Global Trends in Research of Gouty Arthritis Over Past Decade: A Bibliometric Analysis. Front Immunol 2022; 13:910400. [PMID: 35757713 PMCID: PMC9229989 DOI: 10.3389/fimmu.2022.910400] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/17/2022] [Indexed: 01/19/2023] Open
Abstract
Gouty arthritis (GA), as a multifactorial disease, is characterised by intense pain, active inflammation symptoms, and swollen joints. It has utterly complex pathogenesis, of which the amount of research publications on GA has increased during the last few decades. A bibliometric analysis was carried out to investigate the trends, frontiers, and hot spots in global scientific output in GA research over the last decade. We retrieved the Science Citation Index Expanded (SCI-Expanded) of the Web of Science Core Collection (WoSCC) for publications and recorded information published from 2012 to 2021. we carried out the bibliometric analysis and visualisation analysis of the overall distribution of annual outputs, leading countries, active institutions, journals, authors, co-cited references, and keywords with the VOSviewer and CiteSpace. The impact and quality of papers were assessed using a global citation score (GCS). We retrieved 2052 articles and reviews in total. The annual number of publications (Np) related to GA research has increased during the latest decade. China published the most papers, and the USA achieved the highest H-index and number of citations (Nc). The League of European Research Universities (LERU) and Clinical Rheumatology (Clin Rheumatol) are the most productive institutions and periodicals. The total GCS of the paper written by Kottgen, A. in 2013 was 479, ranking the first. The most common keywords were "Gout," "hyperuricemia," and "gouty arthritis." This research revealed that though there was a slight fluctuation in publications related to GA, the Np raised on the whole. China was an enormous creator, and the USA was an influential nation in this domain. The top three contributor authors were Dalbeth, N., Singh, JA., and Choi, HK. There were few investigations on the treatment of GA by Chinese medicine monomer, and the "mechanism," "pathway", "nf- kappa-b", "injury", "receptor", and "animal model" were growing research hotspots. Our research illustrated the hotspots of research and development trends in the research field of GA during the last decade. Recognition of the most critical indicators (researchers, countries, institutes, and journals for the release of GA research), hotspots in the research field of GA can be helpful for countries, scholars, and policymakers in this field to understand GA better make decisions.
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Affiliation(s)
- Pin Deng
- School of Graduates, Beijing University of Chinese Medicine, Beijing, China
| | - Shulong Wang
- School of Graduates, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaojie Sun
- School of Graduates, Beijing University of Chinese Medicine, Beijing, China
| | - Yinze Qi
- Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Zhanhua Ma
- Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Xuyue Pan
- Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Huan Liang
- School of Graduates, Beijing University of Chinese Medicine, Beijing, China
| | - Junde Wu
- Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
| | - Zhaojun Chen
- Department of Hand and Foot Surgery, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
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Risk Factors for Postsurgical Gout Flares after Thoracolumbar Spine Surgeries. J Clin Med 2022; 11:jcm11133749. [PMID: 35807031 PMCID: PMC9267449 DOI: 10.3390/jcm11133749] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/20/2022] [Accepted: 06/23/2022] [Indexed: 11/16/2022] Open
Abstract
Gouty arthritis is the most common form of inflammatory arthritis and flares frequently after surgeries. Such flares impede early patient mobilization and lengthen hospital stays; however, little has been reported on gout flares after spinal procedures. This study reviewed a database of 6439 adult patients who underwent thoracolumbar spine surgery between January 2009 and June 2021, and 128 patients who had a history of gouty arthritis were included. Baseline characteristics and operative details were compared between the flare-up and no-flare groups. Multivariate logistic regression was used to analyze predictors and construct a predictive model of postoperative flares. This model was validated using a receiver operating characteristic (ROC) curve analysis. Fifty-six patients (43.8%) had postsurgical gout flares. Multivariate analysis identified gout medication use (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.14−0.75; p = 0.009), smoking (OR, 3.23; 95% CI, 1.34−7.80; p = 0.009), preoperative hemoglobin level (OR, 0.68; 95% CI, 0.53−0.87; p = 0.002), and hemoglobin drop (OR, 1.93; 95% CI, 1.25−2.96; p = 0.003) as predictors for postsurgical flare. The area under the ROC curve was 0.801 (95% CI, 0.717−0.877; p < 0.001). The optimal cut-off point of probability greater than 0.453 predicted gout flare with a sensitivity of 76.8% and specificity of 73.2%. The prediction model may help identify patients at an increased risk of gout flare.
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Saag KG, Becker MA, White WB, Whelton A, Borer JS, Gorelick PB, Hunt B, Castillo M, Gunawardhana L. Evaluation of Serum Urate Levels and the Clinical Manifestation of Gout with Cardiovascular Mortality from the CARES Trial. Arthritis Rheumatol 2022; 74:1593-1601. [PMID: 35536764 PMCID: PMC9541704 DOI: 10.1002/art.42160] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 04/01/2022] [Accepted: 05/04/2022] [Indexed: 11/30/2022]
Abstract
Objective To investigate whether serum urate levels, number of gout flares, and tophi burden are related to death from cardiovascular (CV) causes after treatment with febuxostat or allopurinol in patients with gout from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients With Gout and Cardiovascular Comorbidities (CARES) trial. Methods Patients were randomly assigned to receive febuxostat (40 mg or 80 mg once daily, according to serum urate levels at week 2) or allopurinol titrated in 100‐mg increments from 200–400 mg or 300–600 mg (with dose determined according to kidney function). Changes from baseline in serum urate level, gout flares, and tophus resolution were key exploratory efficacy parameters in the overall population and in subgroups of patients who died and those who did not die from a CV‐related cause. The latter subgroup included patients who died due to non‐CV causes and those who did not die due to any cause. Results Patients received treatment with febuxostat (n = 3,098) or allopurinol (n = 3,092) for a median follow‐up period of 32 months (for a maximum of 85 months). In the overall population, mean serum urate levels were lower in those receiving febuxostat compared with those receiving allopurinol at most study visits. There were no associations between serum urate levels and death from CV causes with febuxostat. The number of gout flares requiring treatment was higher within 1 year of treatment with febuxostat compared with allopurinol (mean incidence of gout flares per patient‐years of exposure 1.33 versus 1.20), but was comparable thereafter and decreased overall throughout the study period (mean incidence of gout flares per patient‐years of exposure 0.35 versus 0.34 after 1 year of treatment; overall mean incidence 0.68 versus 0.63) irrespective of whether the patient died from a CV‐related cause. Overall, 20.8% of patients had ≥1 tophus at baseline; tophus resolution rates were similar between treatment groups, with cumulative resolution rates of >50%. Conclusion In the CARES trial, febuxostat and allopurinol (≤600 mg doses) had comparable efficacy in patients with gout and CV disease, and there was no evidence of a relationship between death from CV causes and serum urate levels, number of gout flares, or tophus resolution among the patients receiving febuxostat.
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Affiliation(s)
- Kenneth G Saag
- University of Alabama at Birmingham, Birmingham, Alabama
| | - Michael A Becker
- University of Chicago Pritzker School of Medicine, Chicago, Illinois
| | - William B White
- Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut
| | | | - Jeffrey S Borer
- State University of New York Downstate University of the Health Sciences, Brooklyn, New York
| | - Philip B Gorelick
- Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Barbara Hunt
- Takeda Development Center Americas, Inc., Lexington, Massachusetts
| | - Majin Castillo
- Takeda Development Center Americas, Inc., Lexington, Massachusetts
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Villalobos F, Matellan C, Sequeira G, Kerzberg E. Drugs Recommended in Adult Rheumatic Diseases, But Considered for Off-Label Use in Argentina. REUMATOLOGIA CLINICA 2022; 18:286-292. [PMID: 35568442 DOI: 10.1016/j.reumae.2021.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 01/14/2021] [Indexed: 06/15/2023]
Abstract
BACKGROUND Off-label (OL) drug use is the prescription of a drug for indications other than those authorised in its technical datasheet. The objective of this study was to identify drugs recommended in rheumatology but considered for off-label use in Argentina. METHODS A list of medications for certain selected rheumatic conditions was compiled. A drug was considered recommended if it was endorsed by a) at least one Argentine or Pan-American treatment guideline or consensus, or b) two international treatment guidelines, or c) one international treatment guideline and one selected textbook. Approval of these drugs for any condition in Argentina until December 31st, 2018 was explored, and medicines were divided into those with on-label indications and those considered for OL use. RESULTS One hundred and thirty-six medications were analysed in 13 clinical conditions. Sixty-seven OL recommendations (49%) were found, and several drugs had more than one. All the conditions included the recommendation of at least 1 OL drug except osteoporosis and rheumatoid arthritis. The frequency of OL recommendations for the following conditions was 100%: calcium pyrophosphate dihydrate crystal deposition disease, polymyalgia rheumatica, Sjögren syndrome, and systemic sclerosis. The drugs with the highest number of OL recommendations were methotrexate (in 7 conditions), and glucocorticoids and mycophenolate (in 4). There were 2 OL recommendations for rituximab and 1 for abatacept. CONCLUSIONS Almost all the rheumatic disorders analysed involved the recommendation of at least 1 OL medication, and in 4 conditions all the recommendations were OL. Most OL drugs recommended in rheumatology are neither biological nor small-molecule therapies.
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Affiliation(s)
- Fernando Villalobos
- Servicio de Reumatología, Hospital J. M. Ramos Mejia, Urquiza 609, Ciudad Autónoma de Buenos Aires, Argentina
| | - Carla Matellan
- Servicio de Reumatología, Hospital J. M. Ramos Mejia, Urquiza 609, Ciudad Autónoma de Buenos Aires, Argentina
| | - Gabriel Sequeira
- Servicio de Reumatología, Hospital J. M. Ramos Mejia, Urquiza 609, Ciudad Autónoma de Buenos Aires, Argentina.
| | - Eduardo Kerzberg
- Servicio de Reumatología, Hospital J. M. Ramos Mejia, Urquiza 609, Ciudad Autónoma de Buenos Aires, Argentina
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Daoussis D, Kordas P, Varelas G, Michalaki M, Onoufriou A, Mamali I, Iliopoulos G, Melissaropoulos K, Ntelis K, Velissaris D, Tzimas G, Georgiou P, Vamvakopoulou S, Paliogianni F, Andonopoulos AP, Georgopoulos N. ACTH vs steroids for the treatment of acute gout in hospitalized patients: a randomized, open label, comparative study. Rheumatol Int 2022; 42:949-958. [PMID: 35445840 DOI: 10.1007/s00296-022-05128-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 03/25/2022] [Indexed: 11/26/2022]
Abstract
The management of acute gout in the hospital setting may be challenging since most patients are elderly with multiple unstable comorbidities. However, there are no prospective clinical trials for hospitalized patients with gout to guide optimal management. Evidence indicates that steroids or adrenocorticotropic hormone (ACTH) may be effective and safe therapeutic options for these patients. This study aimed at directly comparing the efficacy and safety of ACTH vs betamethasone for the treatment of gout in hospitalized patients. This is the first prospective clinical trial for hospitalized patients with gout. We designed a randomized, open label study to assess the efficacy and safety of a single intramuscular injection of either ACTH or betamethasone in hospitalized patients with acute gout. Primary efficacy endpoints were the change in intensity of pain as recorded using a Visual Analogue Scale (VAS) at baseline compared to 24 h (ΔVAS24h), and 48 h. Moreover, we assessed safety and effects on the hypothalamic-pituitary-adrenal (HPA) axis, glucose and lipid homeostasis, bone metabolism, electrolytes and renal function. 38 patients were recruited. Both treatments were highly effective. The mean ± SE ΔVAS24h and ΔVAS48h for ACTH was 4.48 ± 0.29 and 5.58 ± 0.26, respectively. The mean ± SE ΔVAS24h and ΔVAS48h for betamethasone was 4.67 ± 0.32 and 5.67 ± 0.28, respectively. Direct comparison between the two groups at 24 h and 48 h did not show statistically significant differences. Both treatments were well tolerated and safe. The effects on all metabolic parameters were mostly minimal and transient for both treatments. However, ACTH may affect less the HPA axis and bone metabolism compared to betamethasone, thus leading to the conclusion that. ACTH and betamethasone are effective and safe for the management of acute gout in hospitalized patients but that ACTH may associate with less disturbance of the HPA axis and bone metabolism. Our data support the use of both drugs as first line treatments for hospitalized patients with gout.Clinical trial registration: ClinicalTrials.gov NCT04306653.
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Affiliation(s)
- Dimitrios Daoussis
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Patras, Greece.
| | | | - George Varelas
- Data and Media Lab, Department of Electrical and Computer Engineering, University of Peloponnese, Tripoli, Greece
| | - Marina Michalaki
- Department of Endocrinology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | - Anny Onoufriou
- Department of Microbiology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | - Irene Mamali
- Department of Endocrinology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | - George Iliopoulos
- Department of Rheumatology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | | | | | - Dimitrios Velissaris
- Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | - Giannis Tzimas
- Data and Media Lab, Department of Electrical and Computer Engineering, University of Peloponnese, Tripoli, Greece
| | | | - Sofia Vamvakopoulou
- Department of Microbiology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | - Fotini Paliogianni
- Department of Microbiology, Patras University Hospital, University of Patras Medical School, Patras, Greece
| | | | - Neoklis Georgopoulos
- Department of Endocrinology, Patras University Hospital, University of Patras Medical School, Patras, Greece
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He Y, Dai C, Shen J, Chen Q, Gao J, Pan X, Gan J. Effect of Baihu and Guizhi decoction in acute gouty arthritis: study protocol for a randomized controlled trial. Trials 2022; 23:317. [PMID: 35428324 PMCID: PMC9013133 DOI: 10.1186/s13063-022-06194-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 03/24/2022] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The prevalence rates of gout worldwide have increased annually. Acute gouty arthritis (AGA) accounts for a large proportion of gout patients and causes severe physical and mental pain in patients. Controlling the occurrence and development of gout inflammation is the first step in the treatment of gout. The main treatment drugs in gout are non-steroid anti-inflammatory drugs (NSAIDs), colchicine, and glucocorticoids, but these treatments have many adverse reactions which limit their clinical application. Baihu and Guizhi decoction (BHGZ) is one of the classic prescriptions in the Synopsis of the Golden Chamber and is a good prescription for AGA. Previous clinical studies have shown that BHGZ confers a strong benefit for treating AGA. However, the literature shows a lack of high-quality RCT research on BHGZ with respect to AGA. Therefore, in this study, we use a randomized, double-blind, controlled study with a placebo to evaluate the clinical efficacy and safety of BHGZ on the AGA of moist heat arthralgia spasm syndrome. METHODS This study is a randomized, double-blind, controlled clinical trial. A total of 102 adult participants with AGA of moist heat arthralgia spasm syndrome will be enrolled, with balanced treatment allocation (1:1). The experimental intervention will be BHGZ plus the low-dose colchicine, and the control intervention will be placebo plus the low-dose colchicine for 10 days. To study the clinical efficacy (including VAS score; joint tenderness, joint swelling, joint movement disorder; TCM evidence efficacy score) and the changes of inflammatory indexes. At the same time, the improvement of joint inflammation in patients with AGA will be observed from musculoskeletal ultrasound imaging, and the safety evaluation will be carried out. DISCUSSION This study will be the first placebo-controlled RCT to assess whether BHGZ plus low-dose colchicine have beneficial effects on changing reducing inflammation of joints for patients with AGA of moist heat arthralgia spasm syndrome. The results of this trial will help to provide evidence-based recommendations for clinicians. TRIAL REGISTRATION Chinese Clinical Trials Register ChiCTR1900024974 . Registered on 5 August 2019.
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Affiliation(s)
- Yikun He
- Department of Rheumatism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Chaoran Dai
- Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jiaying Shen
- Department of Rheumatism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Qianwen Chen
- Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jiandong Gao
- Department of Rheumatism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
- Department of Ultrasonography, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
- Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine (14DZ2273200), Shanghai, 201203, China.
| | - Xin Pan
- Department of Rheumatism, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Jing Gan
- Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
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Huang CY, Nicholson MW, Wang JY, Ting CY, Tsai MH, Cheng YC, Liu CL, Chan DZH, Lee YC, Hsu CC, Hsu YH, Yang CF, Chang CMC, Ruan SC, Lin PJ, Lin JH, Chen LL, Hsieh ML, Cheng YY, Hsu WT, Lin YL, Chen CH, Hsu YH, Wu YT, Hacker TA, Wu JC, Kamp TJ, Hsieh PCH. Population-based high-throughput toxicity screen of human iPSC-derived cardiomyocytes and neurons. Cell Rep 2022; 39:110643. [PMID: 35385754 DOI: 10.1016/j.celrep.2022.110643] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 01/13/2022] [Accepted: 03/16/2022] [Indexed: 12/21/2022] Open
Abstract
In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications.
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Affiliation(s)
- Ching Ying Huang
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | | | - Jyun Yuan Wang
- Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
| | - Chien Yu Ting
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Ming Heng Tsai
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Yu Che Cheng
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Chun Lin Liu
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Darien Z H Chan
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Yi Chan Lee
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Ching Chuan Hsu
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Yu Hung Hsu
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Chiou Fong Yang
- Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan
| | - Cindy M C Chang
- Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Shu Chian Ruan
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Po Ju Lin
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Jen Hao Lin
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Li Lun Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Marvin L Hsieh
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Yuan Yuan Cheng
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Wan Tseng Hsu
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - Yi Ling Lin
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Chien Hsiun Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
| | - Yu Hsiang Hsu
- Institute of Applied Mechanics, National Taiwan University, Taipei 106, Taiwan
| | - Ying Ta Wu
- Genomics Research Center, Academia Sinica, Taipei 115, Taiwan
| | - Timothy A Hacker
- Cardiovascular Physiology Core Facility, Department of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Joseph C Wu
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA
| | - Timothy J Kamp
- Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Patrick C H Hsieh
- Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan; Department of Medicine and Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, Madison, WI 53705, USA; Institute of Medical Genomics and Proteomics and Institute of Clinical Medicine, National Taiwan University, Taipei 106, Taiwan.
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Sansone A, Reisman Y, Jannini EA. Relationship between hyperuricemia with deposition and sexual dysfunction in males and females. J Endocrinol Invest 2022; 45:691-703. [PMID: 34997558 PMCID: PMC8741558 DOI: 10.1007/s40618-021-01719-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 12/01/2021] [Indexed: 11/21/2022]
Abstract
PURPOSE The association between gout, the most common crystal arthropathy, and sexual dysfunctions has often been investigated by studies in the last decades. Despite the presence of shared risk factors and comorbidities and the possible effects on sexual health of long-term gout complications, awareness of this association is severely lacking and the pathogenetic mechanisms have only partially been identified. In the present review, we aimed to investigate the current evidence regarding the potential mechanisms linking sexual dysfunctions and gout. METHODS A comprehensive literature search within PubMed was performed to provide a summary of currently available evidence regarding the association between gout and sexual dysfunctions. RESULTS Gout and sexual dysfunctions share several risk factors, including diabesity, chronic kidney disease, hypertension, metabolic syndrome, and peripheral vascular disease. Gout flares triggered by intense inflammatory responses feature severe pain and disability, resulting in worse sexual function, and some, but not all, treatments can also impair sexual health. Long-term gout complications can result in persistent pain and disability due to joint deformity, fractures, or nerve compression, with negative bearing on sexual function. The presence of low-grade inflammation impairs both sex steroids synthesis and endothelial function, further advancing sexual dysfunctions. The psychological burden of gout is another issue negatively affecting sexual health. CONCLUSIONS According to currently available evidence, several biological and psychological mechanisms link sexual dysfunctions and gout. Addressing risk factors and providing adequate treatment could potentially have beneficial effects on both conditions. Appropriate clinical evaluation and multidisciplinary approach are recommended to improve patient care.
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Affiliation(s)
- A Sansone
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133, Rome, Italy
| | - Y Reisman
- Flare-Health, Amstelveen, The Netherlands
| | - E A Jannini
- Chair of Endocrinology and Medical Sexology (ENDOSEX), Department of Systems Medicine, University of Rome Tor Vergata, via Montpellier 1, 00133, Rome, Italy.
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Zhou M, Hua L, Wang YF, Chen ST, Yang CM, Zhang M, Li X, Li B. Oral Huzhang granules for the treatment of acute gouty arthritis: protocol for a double-blind, randomized, controlled trial. Trials 2022; 23:248. [PMID: 35365187 PMCID: PMC8973546 DOI: 10.1186/s13063-022-06188-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 03/20/2022] [Indexed: 11/10/2022] Open
Abstract
Background Acute gouty arthritis (GA) is the main clinical manifestation and the most common initial symptom of gout. The treatment of acute GA involves the use of colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids. Because of the side effects of these drugs, their clinical applications are limited. The use of traditional Chinese medicine for the treatment of acute GA has unique advantages. The aim of this trial is to clarify the treatment efficacy, safety, and recurrence control efficacy of Huzhang granules (HZG) in patients with GA showing dampness-heat syndrome. Methods/design This double-blind, randomized, controlled trial was planned to be conducted between July 1, 2020, and December 31, 2022. A sample size of 267 participants (89 per group) with GA will be randomly assigned to three treatment groups in the ratio of 1:1:1: HZG, etoricoxib, and placebo groups. The study duration is 13 days, including a 1-day screening period, 5-day intervention period, and 1-week follow-up period. The primary outcome is analgesic effectiveness, assessed as pain in the worst-affected joint, which will be measured using the visual analog scale. Secondary outcomes include the patient’s assessment of pain in the primary study joint, patient’s global assessment of response to therapy, investigator’s global assessment of response to therapy, investigator’s assessment of tenderness and swelling of the study joint, and TCM syndromes. Furthermore, the number, nature, and severity of adverse events will be recorded. Discussion This study will provide evidence regarding the clinical efficacy and safety of Chinese medicine treatment for acute gouty arthritis. This study will provide noteworthy findings. Trial registration ClinicalTrials.gov NCT04462666. Registered on July 05, 2020 (first version).
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Affiliation(s)
- Mi Zhou
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Liang Hua
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Yi-Fei Wang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.,Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Si-Ting Chen
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.,Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Chun-Mei Yang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.,Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Ming Zhang
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China
| | - Xin Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. .,Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Bin Li
- Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. .,Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
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Low QJ, Lim TH, Hon SA, Low QJ, Wei MW, Cheo SW, Ramlan AH. Management of gout in the primary care setting. MALAYSIAN FAMILY PHYSICIAN : THE OFFICIAL JOURNAL OF THE ACADEMY OF FAMILY PHYSICIANS OF MALAYSIA 2022; 17:2-9. [PMID: 35440955 PMCID: PMC9004428 DOI: 10.51866/rv1165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting.
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Affiliation(s)
- Qin Jian Low
- MD (UMS), MRCP (UK), Department of Internal Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia.
| | - Tzyy Huei Lim
- MD (FMSMU), MRCP (UK), Department of Internal Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia
| | - Shu Ann Hon
- MD (UNIMAS), Department of Internal Medicine, Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia
| | - Qin Jia Low
- MBBS (Manipal), Klinik Kesihatan Parit Jawa, Parit Jawa, Johor, Malaysia
| | - Mak Woh Wei
- MBBS (IMU), MRCP (UK), Department of Internal Medicine, Hospital Bentong, Bentong, Pahang, Malaysia
| | - Seng Wee Cheo
- MD (UMS), MRCP (UK), Department of Internal Medicine, Hospital Lahad Datu, Lahad Datu, Sabah, Malaysia
| | - Azwarina Hanim Ramlan
- MD (UKM), Doctor in Internal Medicine (UKM), Department of Rheumatology, Hospital Sultanah Bahiyah, Alor Setar, Kedah Darul Aman
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ElSayed S, Jay GD, Cabezas R, Qadri M, Schmidt TA, Elsaid KA. Recombinant Human Proteoglycan 4 Regulates Phagocytic Activation of Monocytes and Reduces IL-1β Secretion by Urate Crystal Stimulated Gout PBMCs. Front Immunol 2022; 12:771677. [PMID: 34992596 PMCID: PMC8725049 DOI: 10.3389/fimmu.2021.771677] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/30/2021] [Indexed: 12/15/2022] Open
Abstract
Objectives To compare phagocytic activities of monocytes in peripheral blood mononuclear cells (PBMCs) from acute gout patients and normal subjects, examine monosodium urate monohydrate (MSU) crystal-induced IL-1β secretion ± recombinant human proteoglycan 4 (rhPRG4) or interleukin-1 receptor antagonist (IL-1RA), and study the anti-inflammatory mechanism of rhPRG4 in MSU stimulated monocytes. Methods Acute gout PBMCs were collected from patients in the Emergency Department and normal PBMCs were obtained from a commercial source. Monocytes in PBMCs were identified by flow cytometry. PBMCs were primed with Pam3CSK4 (1μg/mL) for 24h and phagocytic activation of monocytes was determined using fluorescently labeled latex beads. MSU (200μg/mL) stimulated IL-1β secretion was determined by ELISA. Reactive oxygen species (ROS) generation in monocytes was determined fluorometrically. PBMCs were incubated with IL-1RA (250ng/mL) or rhPRG4 (200μg/mL) and bead phagocytosis by monocytes was determined. THP-1 monocytes were treated with MSU crystals ± rhPRG4 and cellular levels of NLRP3 protein, pro-IL-1β, secreted IL-1β, and activities of caspase-1 and protein phosphatase-2A (PP2A) were quantified. The peritoneal influx of inflammatory and anti-inflammatory monocytes and neutrophils in Prg4 deficient mice was studied and the impact of rhPRG4 on immune cell trafficking was assessed. Results Enhanced phagocytic activation of gout monocytes under basal conditions (p<0.001) was associated with ROS generation and MSU stimulated IL-1β secretion (p<0.05). rhPRG4 reduced bead phagocytosis by normal and gout monocytes compared to IL-1RA and both treatments were efficacious in reducing IL-1β secretion (p<0.05). rhPRG4 reduced pro-IL-1β content, caspase-1 activity, conversion of pro-IL-1β to mature IL-1β and restored PP2A activity in monocytes (p<0.05). PP2A inhibition reversed rhPRG4’s effects on pro-IL-1β and mature IL-1β in MSU stimulated monocytes. Neutrophils accumulated in peritoneal cavities of Prg4 deficient mice (p<0.01) and rhPRG4 treatment reduced neutrophil accumulation and enhanced anti-inflammatory monocyte influx (p<0.05). Conclusions MSU phagocytosis was higher in gout monocytes resulting in higher ROS and IL-1β secretion. rhPRG4 reduced monocyte phagocytic activation to a greater extent than IL-1RA and reduced IL-1β secretion. The anti-inflammatory activity of rhPRG4 in monocytes is partially mediated by PP2A, and in vivo, PRG4 plays a role in regulating the trafficking of immune cells into the site of a gout flare.
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Affiliation(s)
- Sandy ElSayed
- Department of Biomedical and Pharmaceutical Sciences, Chapman University, Irvine, CA, United States
| | - Gregory D Jay
- Department of Emergency Medicine, Rhode Island Hospital, Providence, RI, United States
| | - Ralph Cabezas
- Department of Emergency Medicine, Rhode Island Hospital, Providence, RI, United States
| | - Marwa Qadri
- Department of Pharmacology, School of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Tannin A Schmidt
- Biomedical Engineering Department, University of Connecticut Health Center, Farmington, CT, United States
| | - Khaled A Elsaid
- Department of Biomedical and Pharmaceutical Sciences, Chapman University, Irvine, CA, United States
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