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OBJECTIVE AND DESIGN: To elucidate Sirt1's role in gouty arthritis inflammation and its potential mechanisms. MATERIAL: Constructed murine models of gouty arthritis and conducted THP-1 cell experiments. TREATMENT: 1 mg of MSU crystals injected into mice ankle joints for a 72-h intervention. After a 3-h pre-treatment with Sirt1-specific inhibitor (EX527) and agonist (SRT2104), inflammation was induced for 21 h using lipopolysaccharide (LPS) plus MSU crystals. METHODS: We assessed gouty arthritis severity through joint inflammation index, swelling, and hematoxylin and eosin (H&E) staining, and measured CD68 mononuclear macrophages and Sirt1 expression in synovial tissue via immunohistochemistry. ELISA, NO assay, RT-qPCR, Flow cytometry, and Western blot were utilized to examine macrophage inflammatory factors, polarization, reactive oxygen species(ROS), MAPK/NF-κB/AP-1 and Nrf2/HO-1 pathways proteins. RESULTS: Significant joint swelling, synovial tissue edema, and inflammatory cell infiltration were observed. CD68 mononuclear macrophages and Sirt1 expression were elevated in synovium. Sirt1 activation decreased inflammatory factors, M1 polarization, and ROS generation. Sirt1 activation reduced p38/JNK phosphorylation, thereby inhibiting downstream NF-κB p65/AP-1 and enhancing Nrf2/HO-1, thus suppressing inflammation. CONCLUSIONS: Sirt1 alleviates M1 macrophage polarization and inflammation in gouty arthritis by inhibiting the MAPK/NF-κB/AP-1 pathway and activating the Nrf2/HO-1 pathway. Thus, activating Sirt1 may provide a new therapeutic target for gouty arthritis.
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Artritis Gotosa , Hemo-Oxigenasa 1 , Macrófagos , Factor 2 Relacionado con NF-E2 , FN-kappa B , Sirtuina 1 , Factor de Transcripción AP-1 , Animales , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/metabolismo , Artritis Gotosa/inmunología , Sirtuina 1/metabolismo , Sirtuina 1/genética , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Factor 2 Relacionado con NF-E2/metabolismo , Humanos , Masculino , FN-kappa B/metabolismo , Hemo-Oxigenasa 1/metabolismo , Ratones , Factor de Transcripción AP-1/metabolismo , Células THP-1 , Ratones Endogámicos C57BL , Inflamación , Transducción de Señal/efectos de los fármacos , Lipopolisacáridos/farmacología , Carbazoles , Proteínas de la MembranaRESUMEN
PURPOSE: To evaluate the efficacy and safety of combined glucocorticoids (GCs) and cyclophosphamide (CYC) treatment in Graves' ophthalmopathy (GO). METHODS: We searched PubMed, Embase, Cochrane Library, and four Chinese databases (Chinese National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), WanFang, and SinoMed) for any published randomized controlled trials (RCTs) produced from inception to December 1, 2023. Articles obtained using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria. FINDINGS: We retrieved 1120 records which were eventually reduced to 13 RCTs which were then included in this evaluation. Pooled results indicated that the experimental group (CYC/GCs) showed a higher response rate than control group (GCs or negative control) (RR 1.27; 95% confidence interval 1.19 to 1.37). The subgroup analysis showed that the difference in response rates among treatment protocols (CYC/P, CYC/MPS, CYC/DEX) was not statistically significant (p = 0.23). IMPLICATIONS: The combination of GCs and CYC could be recommended as a therapeutic option for GO, especially in patients who experience recurrence after a withdrawal GCs, have a poor response to GCs, or cannot obtain monoclonal antibody agents for various reasons.
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Glucocorticoides , Oftalmopatía de Graves , Humanos , Glucocorticoides/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , ChinaRESUMEN
OBJECTIVES: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of dermatomyositis (DM) and polymyositis (PM). METHODS: We searched PubMed, Embase, and the China National Knowledge Infrastructure for relevant studies from July 1919 to May 2021. RESULTS: Seventeen papers pertinent to our questions were found: In a meta-analysis, we found that IVIG significantly improved the level of CK (SMD (STD. Mean Difference) = -0.69; 95%CI -0.93, -0.46; P < 0.0001), Manual Muscle Test (SMD = 1.12; 95%CI 0.77, 1.47; P < 0.00001), Medical Research Council (SMD = 1.59; 95%CI 0.86, 2.33; P < 0.00001), Activities of Daily Living (SMD = 1.07; 95%CI 0.59, 1.56; P < 0.0001). The CK levels in DM and PM were also significantly improved after IVIG (SMD = -0.73; 95%CI -1.12, -0.34; P = 0.0002 and SMD = -3.29; 95%CI -5.82, -0.76; P < 0.0001, respectively). The meta-analysis of three RCTs showed that there was a statistically significant improvement after IVIG (SMD = 0.63; 95%CI 0.22, 1.03; P = 0.002). In a random effects model, pooled muscle power improvement rate was 77% (95% CI: 66.0-87.0%). Meta-analyses of IVIG as first-line therapy showed a significant improvement of the CK level (SMD = -0.71; 95%CI -1.12, -0.30; P = 0.0007). The polled improvement rate of oesophageal disorders was 88% (95% CI: 80.0-95.0%). There was no statistically significant difference in the rate of improvement between the number of courses <2 and ≥2 (0.80% vs. 0.80%, P = 0.9). The proportion of corticosteroid-sparing success reached 81.8%. Adverse reactions following IVIG administration are usually mild and transient. Seven patients developed serious adverse events. CONCLUSION: IVIG seems to be an effective drug for DM/PM, improving muscle strength, CK levels, and oesophageal involvement, and it is well tolerated by patients.
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Dermatomiositis , Polimiositis , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Dermatomiositis/tratamiento farmacológico , Actividades Cotidianas , Polimiositis/tratamiento farmacológico , Corticoesteroides/uso terapéuticoRESUMEN
OBJECTIVES: We aimed to review whether PM and DM patients have an increased cardiovascular (CV) risk, including ischaemic heart disease (IHD), cerebrovascular accidents (CVA) and venous thromboembolism. METHODS: We searched PubMed, Embase and the Cochrane database for relevant studies from inception to February 2021. RESULTS: Twenty-two studies comprising 25 433 patients were included. With PM/DM vs general populations, the risk was significantly increased for CV events [relative risk (RR) = 2.37, 95% CI: 1.86, 3.02]. The RR of CV events for males with PM/DM was higher than for females (RR = 1.43; 95% CI: 1.17, 1.74). PM/DM patients followed for one to five years had a significantly higher CV risk than those followed for five to ten years (RR = 3.51, 95% CI: 1.95, 6.32). The risk was increased for North Americans (RR = 4.28, 95% CI: 2.57, 7.11), Europeans (RR = 2.29, 95% CI: 1.58, 3.31) and Asians (RR = 2.03, 95% CI: 1.41, 2.90). Our meta-analysis found that the elevated CV event risk was related to PM (RR = 2.35, 95% CI: 1.51, 3.66) and DM (RR = 2.55, 95% CI: 1.66, 3.93). Subgroup analyses showed that the risk was significantly increased for IHD (RR = 1.76, 95% CI: 1.40, 2.21), CVA morbidity (RR = 1.31, 95% CI: 1.03, 1.67) and ischaemic stroke (IS) (RR = 1.47, 95% CI: 1.26, 1.73), with no statistically significant increased risk of haemorrhagic stroke mortality (RR = 1.43, 95% CI: 0.92, 2.21). The CV event risk was increased for venous thromboembolism (RR = 4.60, 95% CI: 3.17, 6.66), deep venous thrombosis (RR = 5.53, 95% CI: 3.25, 9.39) and pulmonary embolism (RR = 5.26, 95% CI: 2.62, 10.55). CONCLUSION: This meta-analysis found that PM/DM patients had a â¼2.37 times increased CV risk, particularly males diagnosed in the previous five years. PM/DM may be an independent risk factor for developing IHD, IS, deep venous thrombosis and pulmonary embolism.
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Isquemia Encefálica , Dermatomiositis , Isquemia Miocárdica , Polimiositis , Embolia Pulmonar , Accidente Cerebrovascular , Tromboembolia Venosa , Trombosis de la Vena , Adulto , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Dermatomiositis/epidemiología , Femenino , Humanos , Masculino , Polimiositis/complicaciones , Polimiositis/diagnóstico , Polimiositis/epidemiología , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiologíaRESUMEN
WHAT IS KNOWN AND OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc. METHODS: We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria. RESULTS: Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p = 0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p < 0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p = 0.57). WHAT IS NEW AND CONCLUSIONS: We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria).
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Lesión Renal Aguda , Hipertensión Renal , Hipertensión , Esclerodermia Sistémica , Lesión Renal Aguda/inducido químicamente , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Humanos , Hipertensión/complicaciones , Hipertensión Renal/etiología , Hipertensión Renal/terapia , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológicoRESUMEN
Background and Purpose: This meta-analysis aimed to evaluate the therapeutic potential of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over the contralesional hemisphere on upper limb motor recovery and cortex plasticity after stroke. Methods: Databases of PubMed, Medline, ScienceDirect, Cochrane, and Embase were searched for randomized controlled trials published before Jun 31, 2017. The effect size was evaluated by using the standardized mean difference (SMD) and a 95% confidence interval (CI). Resting motor threshold (rMT) and motor-evoked potential (MEP) were also examined. Results: Twenty-two studies of 1 Hz LF-rTMS over the contralesional hemisphere were included. Significant efficacy was found on finger flexibility (SMD = 0.75), hand strength (SMD = 0.49), and activity dexterity (SMD = 0.32), but not on body function (SMD = 0.29). The positive changes of rMT (SMD = 0.38 for the affected hemisphere and SMD = -0.83 for the unaffected hemisphere) and MEP (SMD = -1.00 for the affected hemisphere and SMD = 0.57 for the unaffected hemisphere) were also significant. Conclusions: LF-rTMS as an add-on therapy significantly improved upper limb functional recovery especially the hand after stroke, probably through rebalanced cortical excitability of both hemispheres. Future studies should determine if LF-rTMS alone or in conjunction with practice/training would be more effective. Clinical Trial Registration Information: This trial is registered with unique identifier CRD42016042181.
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Corteza Motora/fisiopatología , Trastornos del Movimiento/rehabilitación , Plasticidad Neuronal , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/complicaciones , Estimulación Magnética Transcraneal , Anciano , Potenciales Evocados Motores , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/etiología , Recuperación de la Función , Resultado del Tratamiento , Extremidad Superior/fisiopatologíaRESUMEN
OBJECTIVE: Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023. RESULTS: Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk. CONCLUSION: Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
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Productos Biológicos , Enfermedades del Tejido Conjuntivo , Diabetes Mellitus , Infecciones Fúngicas Invasoras , Enfermedades Pulmonares Intersticiales , Linfopenia , Humanos , Enfermedades del Tejido Conjuntivo/complicaciones , Ciclofosfamida/efectos adversos , Enfermedades Pulmonares Intersticiales/etiología , Ácido Micofenólico/uso terapéutico , Glucocorticoides/efectos adversos , Factores de Riesgo , Diabetes Mellitus/inducido químicamente , Linfopenia/inducido químicamente , Linfopenia/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/etiologíaRESUMEN
PURPOSE: This study evaluates the tolerability and efficacy of cyclophosphamide (CYC) for the treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We searched PubMed, Embase, Cochrane Library, and 2 Chinese databases (Chinese National Knowledge Infrastructure and SinoMed) for studies published between database inception and September 30, 2021. Articles obtained using the appropriate keywords were independently selected by 2 reviewers on the basis of the established inclusion and exclusion criteria. FINDINGS: In total, 240 records that were eventually curtailed to 13 studies with 83 patients were retrieved and subsequently included in this evaluation. All 13 studies were included in the systematic review, 7 of which were included in the meta-analysis. The pooled estimate of the response rate was 68% (95% CI, 45%-90%). The pooled estimate of the adverse reaction rate was 8% (95% CI, 0%-15%). The disease duration before the first CYC treatment was negatively correlated with the reduction in the modified Rankin Scale score (r = -0.76, P < 0.001). However, the response rates did not differ significantly between patients of different sexes (P = 0.716) or between patients who received and those who did not receive concurrent glucocorticoids (P = 0.617). IMPLICATIONS: CYC might be a recommended therapeutic option for patients with refractory CIDP, especially those who are unable to accept rituximab treatment. Earlier CYC treatment yields better therapeutic outcomes in patients with refractory CIDP without CYC-related contraindications.
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Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Ciclofosfamida/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Rituximab/uso terapéuticoRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. METHODS: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the meta-analysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). CONCLUSIONS: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Esclerodermia Sistémica , Estudios de Cohortes , Humanos , Hipertensión Pulmonar/etiologíaRESUMEN
Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX. Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.
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Background: Although infliximab has been recommended for the second-line treatment of seronegative spondyloarthropathy- or juvenile idiopathic arthritis-related uveitis, the issue of its systemic efficacy and safety in a broader diversity of refractory noninfectious uveitis is debatable. To assess the short-term and relatively long-term efficacy of infliximab in refractory noninfectious uveitis, we performed a systematic review and meta-analysis of observational studies. Methods: PubMed, Cochrane Library, EMBASE, and Wanfang Med Online were systematically searched from January 2005 to March 2020. Two investigators independently assessed eligibility. Data were independently collected by two investigators. The pooled proportions were estimated with patients for intraocular inflammation control and improvement of visual acuity. Pooled proportions with 95% credible intervals were computed. Study homogeneity was investigated using I 2 statistics to quantify the percentage of variation across studies. To pool the results, the Mantel-Haenszel fixed-effects or random-effects models were used. Results: Of 2316 studies identified, 16 unique studies with 509 unique participants were included in the meta-analysis. The pooled proportions of intraocular inflammation control reached 92% (95% CI: 87%-98%; I 2: 1%; p=0.42) and 95% (95% CI: 93%-97%; I 2: 0%; p=0.91) in groups of ≤6- and ≥12-month follow-up durations. During the relatively long follow-up period, the pooled proportions of maintaining visual acuity stable or increasing at least one line reached 99% (95% CI: 96%-100%; I 2: 0%; p=0.54) in the involved eyes. The corticosteroid-sparing effect of infliximab was also well demonstrated, with the proportion of corticosteroid-sparing success reaching 85.5% (112/131). Besides, about serious adverse events, 2.6% (13/500) of patients experienced hypersensitivity reactions, 2.4% (12/500) of patients experienced serious infections, 1.8% (9/500) of patients experienced autoimmune diseases, and 0.6% (3/500) of patients experienced neoplasia. Conclusions: This meta-analysis provided evidence that infliximab might be a promising choice in controlling inflammatory activity, gaining visual acuity, and sparing corticosteroid use with relatively few side effects when applied in treating refractory noninfectious uveitis. Systematic Review Registration: [website], identifier [registration number].
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Objectives: The successful introduction of mycophenolate mofetil (MMF) as a treatment for renal allograft reduced the incidence of acute rejection. The inspiring effects obtained by the MMF have led to an evaluation of its therapeutic potency on ANCA-associated vasculitis (AAV). However, there is little evidence of the MMF's efficacy on the AAV. The meta-analysis is carried out to evaluate the efficacy of MMF as a remission induction therapy in AAV. Methods: Up to June 30th, 2020, PubMed, Cochrane Library, and Embase have been searched comprehensively. According to heterogeneity, the pooled remission rates are synthesized by either fixed-effect or random-effect models. Results: The eight included studies comprising 230 patients who were treated with MMF as induction therapy are included in our analysis. The pooled overall remission rate is 74% (95% CI: 0.68-0.80). The remission rate, the infection rate and the rate of leukopenia of four randomized controlled trials aimed at comparing the effects of MMF with cyclophosphamide (CYC) during induction therapy for AAV have no statistical significance (P > 0.05). Conclusion: MMF may be an alternative to CYC for remission induction therapy in AAV with MPO-ANCA, mild to moderate renal involvement and non-life-threatening state. Whether to observe the effect of MMF in AAV or to compare the difference between MMF and CYC in the future studies, risk stratification and subgrouping of AAV patients should be first carried out to correctly identify the AAV subgroup suitable for MMF.
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Abstract Background: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. Methods: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. Results: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the metaanalysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). Conclusions: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.