BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The informat...BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.展开更多
While exercise capacity in systemic sclerosis with interstitial lung disease could be improved by exercise training, the training outcome of exercise-induced oxygen desaturation has not been examined. The aim of this ...While exercise capacity in systemic sclerosis with interstitial lung disease could be improved by exercise training, the training outcome of exercise-induced oxygen desaturation has not been examined. The aim of this study was to investigate the effect of pulmonary rehabilitation on exercise-induced oxygen desaturation during the six-minute walk test and to detect the factors affecting outcome retrospectively. Patients showing impaired exercise capacity (≤80% of predicted) and/or exercise-induced oxygen desaturation (≤-4% in SpO2) at the end of the six-minute walk test underwent routine walking exercise. Sixteen patients with stable systemic sclerosis completed exercise training for 55 days on average. The mean six-minute walk distance improved from 467 m to 502 m (P = 0.0012). The improvement in distance was negatively related to baseline distance (R2 = 0.28, P = 0.037), but was not related to parameters from pulmonary function tests and echocardiograms. Oxygen saturation was normal at rest, but was decreased in fifteen patients at the end of the test. Exercise-induced oxygen desaturation was positively related to the diffusion capacity of the lungs for carbon monoxide at baseline (R2 = 0.33, P = 0.026);however, it was not related to any cardiopulmonary parameters after intervention. Seven of sixteen patients ameliorated exercise-induced oxygen desaturation or showed no oxygen desaturation after exercise training, while others deteriorated. No cardiopulmonary parameters affected the training outcome of exercise-induced oxygen desaturation. Exercise train ing was beneficial in improving exercise tolerance, but training effects and mechanisms on exercise-induced oxygen desaturation still need more studies to be explained.展开更多
Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease,...Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.展开更多
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
Evidence suggests that B cells may participate in the fibrotic process Based on this experimental evidence, treatment with rituximab(RTX) has been tried in systemic sclerosis(SSc) with promising results. In a randomiz...Evidence suggests that B cells may participate in the fibrotic process Based on this experimental evidence, treatment with rituximab(RTX) has been tried in systemic sclerosis(SSc) with promising results. In a randomized controlled study from our research group it was shown that treatment with 2 courses of RTX leads to a significant improvement of lung function at 1 year compared to baseline. All relevant studies have so far reported clinical and/or histologic improvement of skin fibrosis something that adds further evidence in favor of a disease modifying role of RTX in SSc. It is more than obvious that novel therapies for SSc-associated lung disease are needed. A large scale, randomized, controlled study assessing the efficacy of RTX in SSc associated interstitial lung disease is warranted. If RTX turns out to be effective it would be a major therapeutic advance in SSc since it can be administered on a long term basis due to its acceptable safety profile.展开更多
Introduction: Predictors of lung function decline in systemic sclerosis (SSc) are unknown. Serum pneumoprotein levels, surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6), correlate with pulmonary damage. We...Introduction: Predictors of lung function decline in systemic sclerosis (SSc) are unknown. Serum pneumoprotein levels, surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6), correlate with pulmonary damage. We aimed to test whether levels can predict rapid lung function decline in SSc. Methods: SSc patients who had serial pulmonary function tests (PFT) were analyzed for SP-D and KL-6 levels by enzyme linked immunosorbent assay. Levels were correlated with an annual rate of decline in % predicted forced vital capacity (FVC) of >﹣2% (out-come);controls did not experience this FVC decline. Uni- and multi-variate analysis, adjusting for age, disease duration, gender, baseline % predicted FVC, SP-D, and KL-6, was performed. Results are reported as mean ± SD. Results: Thirty three cases and 25 controls had a disease duration of 8.8 ± 7.3 and 8.3 ± 6.1 years, respectively. In adjusted analyses, lung function decline correlated with greater baseline FVC OR = 1.03 [95% CI of 1.00-1.07];a trend towards significance was observed for greater levels of SP-D with FVC decline, OR = 1.37 [95% CI of 0.96-2.12]. Conclusion: Our data provide evidence that SSc patients with long-standing disease are still at risk for lung function decline and SP-D levels may predict lung function decline.展开更多
Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Method...Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Methods:A retrospective records review of clinicodemographic,laboratory,and outcome data of SSc patients attending a state-funded tertiary Rheumatology service in South Africa.Results:Most of the 164 patients were Black(92.7%)and female(87.8%).The mean(SD)age at diagnosis and follow-up duration were 42.6(12.9)and 5.5(5.6)years,respectively.The majority(75.6%)had diffuse cutaneous SSc(dcSSc);and digital pits/ulcers,interstitial lung disease(ILD),and pulmonary hypertension(PH)were documented in 73.6%,55.0%,and 38.3%,respectively.There were 56 known deaths and an equal number of patients were lost to follow-up.Deaths resulted from ILD complicated by PH(42.9%),infections(8.9%),cardiac disease(7.1%),and malignancies(3.6%).Estimated 5-and 10-year survival rates for patients with known outcomes were 58%and 42%,respectively.Independent predictors of death were renal dysfunction and cor pulmonale.Conclusion:Most patients in this study of South Africans had dcSSc and poor outcomes.Known deaths resulted from cardiorespiratory complications of ILD complicated by PH.Cor pulmonale and renal dysfunction were independent predictors of death.展开更多
基金Supported by the Ministry of Science and Higher Education of the Russian Federation,No.075-15-2022-301.
文摘BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.
文摘While exercise capacity in systemic sclerosis with interstitial lung disease could be improved by exercise training, the training outcome of exercise-induced oxygen desaturation has not been examined. The aim of this study was to investigate the effect of pulmonary rehabilitation on exercise-induced oxygen desaturation during the six-minute walk test and to detect the factors affecting outcome retrospectively. Patients showing impaired exercise capacity (≤80% of predicted) and/or exercise-induced oxygen desaturation (≤-4% in SpO2) at the end of the six-minute walk test underwent routine walking exercise. Sixteen patients with stable systemic sclerosis completed exercise training for 55 days on average. The mean six-minute walk distance improved from 467 m to 502 m (P = 0.0012). The improvement in distance was negatively related to baseline distance (R2 = 0.28, P = 0.037), but was not related to parameters from pulmonary function tests and echocardiograms. Oxygen saturation was normal at rest, but was decreased in fifteen patients at the end of the test. Exercise-induced oxygen desaturation was positively related to the diffusion capacity of the lungs for carbon monoxide at baseline (R2 = 0.33, P = 0.026);however, it was not related to any cardiopulmonary parameters after intervention. Seven of sixteen patients ameliorated exercise-induced oxygen desaturation or showed no oxygen desaturation after exercise training, while others deteriorated. No cardiopulmonary parameters affected the training outcome of exercise-induced oxygen desaturation. Exercise train ing was beneficial in improving exercise tolerance, but training effects and mechanisms on exercise-induced oxygen desaturation still need more studies to be explained.
文摘Interstitial lung disease(ILD) is an important mani-festation of collagen vascular diseases. It is a common feature of scleroderma, and also occurs in dermatomyositis and polymyositis, mixed connective tissue disease, Sjogren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, and Antineutrophil cytoplasmic antibody-associated vasculitis. When present, it is associated with increased morbidity and mortality, thus making early diagnosis important. In fact, in many patients, ILD may be the first manifestation of a collagen vascular disease. The most common symptoms are cough and dyspnea. The diagnosis is made based on pulmonary function tests showing restrictive lung disease and impaired oxygen diffusion and chest imaging showing ground glass infiltrates, interstitial thickening, and/or fibrosis. The most common histologic finding on lung biopsy is non-specific interstitial pneumonia, though organizing pneumonia and usual interstitial pneumonia may also be seen. Treatment is focused on addressing the underlying collagen vascular disease with immunosuppression, either with corticosteroids or a steroid-sparing agent such as cyclophosphamide, azathioprine, or mycophenolate, although the optimal agent and duration of therapy is not known. There are few clinical trials to guide therapy that focus specifically on the progression of ILD. The exception is in the case of scleroderma-associated ILD, where cyclophosphamide has been shown to be effective.
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
文摘Evidence suggests that B cells may participate in the fibrotic process Based on this experimental evidence, treatment with rituximab(RTX) has been tried in systemic sclerosis(SSc) with promising results. In a randomized controlled study from our research group it was shown that treatment with 2 courses of RTX leads to a significant improvement of lung function at 1 year compared to baseline. All relevant studies have so far reported clinical and/or histologic improvement of skin fibrosis something that adds further evidence in favor of a disease modifying role of RTX in SSc. It is more than obvious that novel therapies for SSc-associated lung disease are needed. A large scale, randomized, controlled study assessing the efficacy of RTX in SSc associated interstitial lung disease is warranted. If RTX turns out to be effective it would be a major therapeutic advance in SSc since it can be administered on a long term basis due to its acceptable safety profile.
文摘Introduction: Predictors of lung function decline in systemic sclerosis (SSc) are unknown. Serum pneumoprotein levels, surfactant protein-D (SP-D) and Krebs von den Lungen-6 (KL-6), correlate with pulmonary damage. We aimed to test whether levels can predict rapid lung function decline in SSc. Methods: SSc patients who had serial pulmonary function tests (PFT) were analyzed for SP-D and KL-6 levels by enzyme linked immunosorbent assay. Levels were correlated with an annual rate of decline in % predicted forced vital capacity (FVC) of >﹣2% (out-come);controls did not experience this FVC decline. Uni- and multi-variate analysis, adjusting for age, disease duration, gender, baseline % predicted FVC, SP-D, and KL-6, was performed. Results are reported as mean ± SD. Results: Thirty three cases and 25 controls had a disease duration of 8.8 ± 7.3 and 8.3 ± 6.1 years, respectively. In adjusted analyses, lung function decline correlated with greater baseline FVC OR = 1.03 [95% CI of 1.00-1.07];a trend towards significance was observed for greater levels of SP-D with FVC decline, OR = 1.37 [95% CI of 0.96-2.12]. Conclusion: Our data provide evidence that SSc patients with long-standing disease are still at risk for lung function decline and SP-D levels may predict lung function decline.
文摘Background:There is a dearth of mortality data on systemic sclerosis(SSc)in sub-Saharan Africa.We undertook a retrospective study of causes and predictors of death in low-income indigent South Africans with SSc.Methods:A retrospective records review of clinicodemographic,laboratory,and outcome data of SSc patients attending a state-funded tertiary Rheumatology service in South Africa.Results:Most of the 164 patients were Black(92.7%)and female(87.8%).The mean(SD)age at diagnosis and follow-up duration were 42.6(12.9)and 5.5(5.6)years,respectively.The majority(75.6%)had diffuse cutaneous SSc(dcSSc);and digital pits/ulcers,interstitial lung disease(ILD),and pulmonary hypertension(PH)were documented in 73.6%,55.0%,and 38.3%,respectively.There were 56 known deaths and an equal number of patients were lost to follow-up.Deaths resulted from ILD complicated by PH(42.9%),infections(8.9%),cardiac disease(7.1%),and malignancies(3.6%).Estimated 5-and 10-year survival rates for patients with known outcomes were 58%and 42%,respectively.Independent predictors of death were renal dysfunction and cor pulmonale.Conclusion:Most patients in this study of South Africans had dcSSc and poor outcomes.Known deaths resulted from cardiorespiratory complications of ILD complicated by PH.Cor pulmonale and renal dysfunction were independent predictors of death.
