***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 Interstitial lung disease ( ILD ) is a noteworthy condition in the treatment of systemic sclerosis ( SSc ) because of its associated mortality and morbidity ; however , the efficacy of various treatments for ILD has been controversial in previous reports . In this study , we examined the efficacy and safety of intravenous cyclophosphamide ( IVCY ) pulse therapy with prednisolone ( PSL ) for the treatment of ILD with SSc . A total of 121 patients with SSc were screened and evaluated for ILD , using high-resolution computed tomography of the chest , pulmonary function testing , and bronchoalveolar lavage . Thirteen patients with active ILD were enrolled in this study . The treatment protocol for ILD was 0.4 g/m2 of body surface area of IVCY monthly plus 0.8 mg/kg of body weight of PSL daily . Two to six doses of IVCY were administered , depending on the remission of ILD . Initial PSL doses were maintained for a month and then gradually tapered to 10 mg daily . An activity index of ILD showed improvements in all patients in the 12 months after the initial intervention ; however , four patients experienced recurrence of ILD after 24 months , and one additional patient had recurrence of ILD after 36 months . Seven patients reached the 48-month point with no recurrence of ILD . This long observational study for 48 months showed the efficacy of IVCY with PSL  for active alveolitis in the first year . However , because five patients had recurrence of ILD more than 1 year after the treatment , it would be necessary to consider maintenance therapy for ILD beyond 1 year 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 Thirty-five patients with diffuse systemic sclerosis were studied in a r and omized , placebo-controlled , double-blind study . Seventeen patients received intravenous dexamethasone “ pulse ” therapy , while 18 patients received placebo . Each “ pulse ” consisted of 100 mg dexamethasone in 250 ml 5 % dextrose infused intravenously over 1 h. Pulse therapy was repeated every month for 6 months . Assessment of disease status with various parameters was done at entry and at completion of trial , i.e. after 6 months . Significant improvement in skin involvement was seen in the study group , with the total skin score ( TSS ) decreasing from 28.5±12.2 to 25.8±12.8 , while in the control group , TSS increased from 30.6±13.2 to 34.7±10 . Similarly , significant improvement was noted in the flexion index . Other parametres that included extension index , maximum oral opening , range of movement of joints , functional disability score , Raynaud 's phenomenon ( frequency and duration ) , ESR , proteinuria , chest X-ray , ECG , lung function tests , barium swallow and antinuclear antibody were unchanged . Adverse effects of therapy were limited to an increased incidence of minor chest infections . It is concluded that intravenous pulse dexamethasone may be useful in the treatment of diffuse systemic sclerosis 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 Objective : Interstitial lung disease ( ILD ) frequently complicates systemic sclerosis ( SSc ) . Cyclophosphamide ( CYC ) is a promising immunosuppressive therapy for SSc-related ILD . Our objective was to investigate the effectiveness of an intravenous CYC ( iv CYC ) pulse regime in SSc-related ILD during treatment and thereafter . Methods : In a prospect i ve observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months . Clinical status , pulmonary functional testing ( PFT ) and high resolution computed tomography ( H RCT ) of the chest were evaluated at enrolment and 6 , 12 and 24 months thereafter . After treatment withdrawal , patients were followed up every 6 months with PFT and chest H RCT to monitor lung disease . Results : Clinical improvement was apparent in 8 out of 10 patients . The median values of forced vital capacity ( FVC ) , forced expiratory volume in the first second ( FEV1 ) and diffusion lung capacity for carbon monoxide ( DLCO ) as well as ground-glass pattern on H RCT did not change significantly after 6 , 12 and 24 months of therapy . The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months ( range : 12 - 48 months ) . The final median FVC was 54.5 % of predicted value ( interquartile range , IQR= 31.6%-94 % ) . Only one patient suffered a FVC d 
    Output:
    
Despite the limited evidence for their effectiveness , GC are frequently prescribed in SSc patients , mostly in those with the diffuse subset .