***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract : Until recently , renal crisis was the most significant cause of morbidity and mortality in patients with scleroderma ( SSc ) . Nowadays , following the introduction of angiotensin-converting enzyme inhibitors used in renovascular hypertension , pulmonary fibrosis and pulmonary hypertension have become the most common causes of death in SSc . Consequently , the early diagnosis and treatment of pulmonary fibrosis is essential to improve morbidity and mortality in SSc patients . The aim of this study was to investigate the effect of intravenous cyclophoshamide pulse therapy in patients with SSc and evidence of active alveolitis assessed on a high resolution computed tomographic ( H RCT ) scan , and to compare the effect of cyclophosphamide pulse therapy with oral therapy .  Sixteen consecutive patients with SSc were allocated alternately to the two treatment groups . Eight patients were treated with monthly cyclophoshamide pulse therapy ( 750 mg/m2 ) for 12 months ; the other eight patients were treated with oral cyclophosphamide ( 2–2.5 mg/kg/day ) for the same period . All patients received concurrently prednisone ( 10 mg/day ) . Pulmonary function tests and H RCT scans were performed before therapy and at 6 and 12 months . In the oral cyclophosphamide group , three patients with a grade I pattern showed regression of disease extent . In the other five patients ( one with grade II and four with grade III ) the pattern and extent of disease remained stable during the study . No statistical differences were found in forced expiratory volume in 1 s , forced vital capacity and total lung capacity during the study period . The diffusing capacity for carbon monoxide increased significantly between baseline and 12 months ( p= 0.043 ) . In the cyclophosphamide pulse therapy group , seven patients with a grade I pattern showed regression of disease extent at 6 months ( p= 0.018 ) and 12 months ( p= 0.012 ) . One patient with grade III remained stable during the study . In both groups the regression of the extent of disease estimated on H RCT was due to a decrease in the ground glass appearance . The extent of the reticular appearance remained stable throughout the study . Our results indicate that cyclophosphamide pulse therapy is effective in suppressing active alveolitis ( ground glass appearance ) . Although in this study it is not possible to compare pulse therapy with oral therapy because of the different pattern seen on H RCT between the two groups , it seems that oral therapy is also effective in suppressing active alveolitis . Neither regimen improved pulmonary involvement when the reticular appearance predominated over the ground glass appearance on H RCT . It is concluded that either pulse or oral cyclophosphamide therapy may improve the outcome of SSc patients OBJECTIVE To evaluate the safety and efficacy of monthly intravenous pulses of cyclophosphamide ( CP ) in combination with low or high doses of prednisolone in patients with systemic sclerosis ( SSc ) related interstitial lung disease ( ILD ) with FVC < 70 % of predicted . METHODS An open label , non-parallel arm study , performed in the rheumatology outpatient clinic of a university hospital . Twenty-eight patients with SSc related ILD were evaluated . Endpoint evaluations included the evolution of high resolution computed tomography , pulmonary function tests , skin involvement and dyspnea over 12 months . Patients were treated with monthly IV CP in combination with prednisolone at low ( < 10 mg/day ; n = 12 ) or high doses ( 1 mg/kg/day for 4 weeks , then reducing the prednisolone by 5 mg/day on alternating days each 2 weeks ; n = 16 ) . RESULTS In the low dose steroid group , no improvement was seen for any endpoint at 6 and 12 months of followup . In the high dose steroid group , at 12 months there was significant improvement in the percentage of " ground glass " parenchymal lung involvement ( -5.7 % ; p = 0.003 ) , as well as in the percentage of predicted FVC ( 12.4 % ; p < 0.001 ) , the percentage of predicted DLCO ( 7.3 % ; p = 0.029 ) , the percentage of skin involvement ( -5.4 % ; p = 0.01 ) , and the severity of dyspnea ( p = 0.012 ) . Substantial improvement was seen as early as 6 months . One patient ( low dose group ) died from ILD . CONCLUSION A combination of IV pulse CP with high doses of prednisolone shows promising efficacy in improving the clinical , physiological , and radiological evolution of SSc related ILD with reversal of the underlying alveolitis Lung involvement constitutes nowadays the major cause of morbidity and mortality in scleroderma patients . Pulmonary fibrosis in systemic sclerosis ( SSc ) is thought to be the consequence of interstitial inflammation . Early diagnosis and treatment of active alveolitis is essential to prevent the deterioration of pulmonary function , improving outcome in SSc patients . The aim of the study was to investigate the effect of 1-year treatment with oral cyclophosphamide ( CYC ) on the evolution of interstitial lung disease in scleroderma patients with a diagnosis of active alveolitis . An open-label one-arm monocenteric study was conducted on 33 scleroderma patients with active alveolitis — defined as the presence of areas of ‘ ground-glass attenuation ’ on high-resolution computed tomography and a recent deterioration in lung function — treated with oral CYC 2 mg kg−1 day−1 for 1 year and medium-low dose steroids ( prednisone 25 mg for 3 months and then tapered to 5 mg/day ) . Results showed that diffusing capacity for carbon monoxide ( DLco ) values remained stable after 6 months of treatment and significantly increased after 12 months ( 2.06±1.38 , 2.21±1.62 and 2.39±1.64 mmol/min/kPa , at baseline/6/12 months , respectively ; p<0.001 12th month vs baseline ) vital capacity ( VC ) values slightly increased ( i.e. stabilised ) in the same time frame ( 2.46±0.71 , 2.41±0.76 and 2.56±0.75 l ) . Accordingly , the vast majority of our patients ( n=29 , 87.9 % ) presented a DLco and /or a VC improvement or stabilisation with respect to baseline . Favourable results were more likely to be observed in patients with a lower Wells ’ radiological grade ( grade I ) . In 25 patients followed up for further 12 months after the interruption of therapy , VC and DLco remained stable . Thus , long-term therapy with oral CYC is effective in ameliorating and /or stabilising lung function in scleroderma patients with active alveolitis , with beneficial effects lasting up to 1 year after interruption . The higher efficacy in those patients with an early pulmonary disease stage and a lower radiological grade underlies the importance of an early diagnosis and intervention OBJECTIVE The lack of r and omized controlled trials ( RCTs ) in pulmonary fibrosis in systemic sclerosis ( SSc ) has hampered an evidence -based approach to treatment . This RCT was undertaken to investigate the effects of intravenous ( IV ) cyclophosphamide ( CYC ) followed by azathioprine ( AZA ) treatment in pulmonary fibrosis in SSc . METHODS Forty-five patients were r and omized to receive low-dose prednisolone and 6 infusions ( monthly ) of CYC followed by oral AZA , or placebo . Primary outcome measures were change in percent predicted forced vital capacity ( FVC ) and change in single-breath diffusing capacity for carbon monoxide ( DLCO ) . Secondary outcome measures included changes in appearance on high-resolution computed tomography and dyspnea scores . An intent-to-treat statistical analysis was performed . RESULTS At baseline , there were no significant group differences in factors linked to outcome , including severity of pulmonary fibrosis and autoantibody status . Sixty-two percent of the patients completed the first year of treatment . Withdrawals included 9 patients ( 6 from the placebo group ) with significant decline in lung function , 2 with treatment side effects ( both from the active treatment group ) , and 6 with non-trial-related comorbidity . No hemorrhagic cystitis or bone marrow suppression was observed . Estimation of the relative treatment effect ( active treatment versus placebo ) adjusted for baseline FVC and treatment center revealed a favorable outcome for FVC of 4.19 % ; this between-group difference showed a trend toward statistical significance ( P = 0.08 ) . No improvements in DLCO or secondary outcome measures were identified . CONCLUSION This trial did not demonstrate significant improvement in the primary or secondary end points in the active treatment group versus the group receiving placebo . However , for FVC there was a trend toward statistical significance between the 2 groups . This suggests that treatment of pulmonary fibrosis in SSc with low-dose prednisolone and IV CYC followed by AZA stabilizes lung function in a subset of patients with the disease . Therapy was well tolerated with no increase in serious adverse events Current therapeutic modalities for the treatment of systemic sclerosis ( SSc ) have significant limitations . The window of opportunity to prevent tissue fibrosis and irreversible damage occurs during the early inflammatory phase of this condition . A drug that we believe has promise to exert a desired effect in early SSc is cyclophosphamide ( CYC ) . However , there are only a few published reports regarding the use of cytotoxic immunosuppressive medications at the onset of the illness . The goal of this study was to test the efficacy and toxicity of CYC in patients with early diffuse SSc . The study design was a r and omized , unblinded , 18 months per patient trial with a comparison group that received azathioprine ( AZ ) .  Thirty patients were assigned to receive oral CYC  ( 2 mg/ kg daily for 12 months and then maintained on 1 mg/kg daily ) and 30 patients were assigned to receive  oral AZ ( 2.5 mg/kg daily for 12 months and then maintained on 2 mg/kg daily ) . During first 6 months of the trial , the patients also received prednisolone , which was started at a dosage of 15 mg daily and tapered to zero by the end of the sixth month . After treatment there was a statistically significant improvement in the modified Rodnan skin score ( MRSS ) , attack frequency of Raynaud ’s phenomenon ( RP ) , and erythrocyte sedimentation rate ( ESR ) in the CYC-group , but not in the AZ-group . The forced vital capacity ( FVC ) and carbon monoxide diffusing capacity ( DLCO ) did not change after treatment in the CYC-group , but statistically significantly worsened in the AZ-group . No life-threatening or irreversible adverse reactions were observed in either group . This study showed that CYC is a promising disease modifying medication for SSc as it exhibited a positive influence on the evolution of disease BACKGROUND We conducted a double-blind , r and omized , placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease . METHODS At 13 clinical centers throughout the United States , we enrolled 158 patients with scleroderma , restrictive lung physiology , dyspnea , and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid , thoracic high-resolution computed tomography , or both . Patients received oral cyclophosphamide ( < or = 2 mg per kilogram of body weight per day ) or matching placebo for one year and were followed for an additional year . Pulmonary function was assessed every three months during the first year , and the primary end point was the forced vital capacity ( FVC , expressed as a percentage of the predicted value ) at 12 months , after adjustment for the baseline FVC . RESULTS Of 158 patients , 145 completed at least six months of treatment and were included in the analysis . The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent ( 95 percent confidence interval , 0.28 to 4.79 percent ) , favoring cyclophosphamide ( P<0.03 ) . There were also treatment-related differences in physiological and symptom outcomes , and the difference in FVC was maintained at 24 months . There was a greater frequency of adverse events in the cyclophosphamide group , but the difference between the two groups in the number of serious adverse events was not significant . CONCLUSIONS One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function , dyspnea , thickening of the skin , and the health-related quality of life . The effects on lung function were maintained through the 24 months of the study Objective : To investigate the efficacy of a treatment with low‐dose intravenous cyclophosphamide ( CYC ) and low‐dose prednisone in early diffuse cutaneous systemic sclerosis ( dcSSc ) . Methods : Patients with dcSSc and a disease duration < 24 months consecutively admitted to a tertiary centre underwent a prospect i ve 1‐year study . They were treated with i.v . CYC 500 mg/pulses , 10 mg prednisone equivalent , and supportive therapy . Modified Rodnan skin score ( mRss ) , Health Assessment Question naire – Disability Index ( HAQ‐DI ) , forced vital capacity ( FVC ) , and diffusing lung capacity 
    Output:
    
Conclusions Cyclophosphamide  treatment in patients with systemic sclerosis-related interstitial lung disease does not result in clinical ly significant improvement of pulmonary function