human
***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: PURPOSE This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy ( HTO ) for varus deformity , with or without mesenchymal stem cell ( MSC ) therapy .  METHODS This prospect i ve , comparative observational study was design ed to evaluate the effectiveness of MSC therapy . The patients were divided into 2 groups : HTO with platelet-rich plasma ( PRP ) injection only ( n = 23 ) or HTO in conjunction with MSC therapy and PRP injection ( n = 21 ) . Prospect i ve evaluations of both groups were performed using the Lysholm score , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and a visual analog scale ( VAS ) score for pain . Second-look arthroscopy was carried out in all patients at the time of metal removal . RESULTS The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain ( PRP only , 74.0 ± 5.7 ; MSC-PRP , 81.2 ± 6.9 ; P < .001 ) and symptoms ( PRP only , 75.4 ± 8.5 ; MSC-PRP , 82.8 ± 7.2 ; P = .006 ) relative to the PRP-only group . Although the mean Lysholm score was similarly improved in both groups ( PRP only , 80.6 ± 13.5 ; MSC-PRP , 84.7 ± 16.2 ; P = .357 ) , the MSC-PRP group showed a significantly greater improvement in the VAS pain score  ( PRP only , 16.2 ± 4.6 ; MSC-PRP , 10.2 ± 5.7 ; P < .001 ) . There were no differences in the preoperative ( PRP only , varus 2.8 ° ± 1.7 ° ; MSC-PRP , varus 3.4 ° ± 3.0 ° ; P = .719 ) and postoperative ( PRP only , valgus 9.8 ° ± 2.4 ° ; MSC-PRP , valgus 8.7 ° ± 2.3 ° ; P = .678 ) femorotibial angles or weight-bearing lines between the groups . Arthroscopic evaluation , at plate removal , showed that partial or even fibrocartilage coverage was achieved in 50 % of the MSC-PRP group patients but in only 10 % of the patients in the PRP-only group ( P < .001 ) . CONCLUSIONS MSC therapy , in conjunction with HTO , mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Introduction Knee osteoarthritis ( OA ) is the most common articular disease . Different methods are used to alleviate the symptoms of patients with knee OA , including analgesics , physical therapy , exercise prescription , and intra-articular injections ( glucocorticoids , hyaluronic acid [ HA ] , etc ) . New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage , including the use of platelet-rich plasma ( PRP ) as a complex of growth factors . Due to the high incidence of OA and its consequences , we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA . Method This non-placebo-controlled r and omized clinical trial involved 160 patients affected by knee OA , grade 1–4 of Kellgren – Lawrence scale . In the PRP group ( n = 87 ) , two intra-articular injections at 4-week interval were applied , and in the HA group ( n = 73 ) , three doses of intra-articular injection at 1-week interval were applied . All patients were prospect ively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) and SF-36 question naires . The results were analyzed using SPSS 16.1 software ( RCT code : I RCT 2014012113442N5 ) . Results At the 12-month follow-up , WOMAC pain score and bodily pain significantly improved in both groups ; however , better results were determined in the PRP group compared to the HA group ( P < 0.001 ) . Other WOMAC and SF-36 parameters improved only in the PRP group . More improvement ( but not statistically significant ) was achieved in patients with grade 2 OA in both the groups . Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment Purpose To assess the outcome of intra-articular platelet-rich plasma ( PRP ) injections into the knee in patients with early stages of osteoarthritis ( OA ) and to determine whether cyclical dosing would affect the end result . Methods This is a prospect i ve , r and omized study in which 93 patients ( 119 knees ) were followed up for a minimum of 2 years . Fifty knees were r and omly selected prior to the first injection , to receive a second cycle at the completion of 1 year . A cycle consisted of three injections , each given at a monthly interval . The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , Visual Analogue Scale ( VAS ) , Tegner and Marx scoring systems , recorded prior to the first injection and then at 12 , 18 and 24 months . Results There was a significant improvement in all scores over time compared to the pre-treatment value ( p < 0.001 ) . At 12 months , both groups showed similar and significant improvement . At 18 months , except for KOOS ( Symptoms ) and Tegner score , all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle ( p < 0.001 ) . At 2 years , the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores . Conclusion Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option . There is a significant reduction in pain and improvement in function after 12 months , which can be further improved at 18 months by annual repetition of the treatment . Although the beneficial effects are ill sustained at 2 years , the results are encouraging when compared to the pre-treatment function . Level of evidence II We design ed a r and omized clinical trial with control group , to investigate the effects of platelet rich plasma ( PRP ) on pain , stiffness , function and quality of life in patients with knee osteoarthritis . Patients were r and omly divided in two groups . For both groups of participants , therapeutic exercise was prescribed . In the PRP group , two courses of leukocyte rich PRP ( 5.6 fold higher platelet concentration ) with a 4-week interval was injected . For each participant , Western Ontario and McMaster University ’s Arthritis Index ( WOMAC ) and the SF-36 question naire ( Farsi version ) were filled at the baseline and 6 months after treatments . Thirty-one patients in the PRP group and 31 patients in the control group were studied .  Mean changes of total WOMAC , physical component summery and mental component summery of Short Form-36 in PRP group showed better improvement than control group ( P<0.05 ) . This study showed that intra articular PRP knee injection combined with therapeutic exercise can be more effective in pain reduction and improvement of stiffness and quality of life , compared with therapeutic exercise alone Purpose This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis ( OA ) given an intra-articular injection of platelet-rich plasma ( PRP ) , hyaluronic acid ( HA ) or ozone gas . Methods A total of 102 patients with mild – moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were r and omly separated into three groups . Group 1 ( PRP group ) received intra-articular injection of PRP × 2 doses , Group 2 ( HA group ) received a single dose of HA , and Group 3 ( Ozone group ) received ozone × four doses . Weight-bearing anteroposterior – lateral and Merchant ’s radiographs of both knees were evaluated . WOMAC and VAS scores were applied to all patients on first presentation and at 1 , 3 , 6 and 12 months . Results At the end of the 1st month after injection , significant improvements were seen in all groups . In the 3rd month , the improvements in WOMAC and VAS scores were similar in Groups 1 and 2 , while those in Group 3 were lower ( p < 0.001 ) . At the 6th month , while the clinical efficacies  of PRP and HA were similar and continued , the clinical effect of ozone had disappeared ( p < 0.001 ) . At the end of the 12th month , PRP was determined to be both statistically and clinical ly superior to HA ( p < 0.001 ) . Conclusion In the treatment of mild – moderate knee OA , PRP was more successful than HA and ozone injections , as the application alone was sufficient to provide at least 12 months of pain-free daily living activities . Level of evidence Therapeutic study , Level UNLABELLED : Osteoarthritis ( OA ) is the most widespread musculoskeletal disorder in adults . It leads to cartilage damage associated with subchondral bone changes and synovial inflammation , causing pain and disability . The present study aim ed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells ( ASCs ) in patients with knee OA , as well as clinical efficacy as secondary endpoint . A bicentric , uncontrolled , open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries . From April 2012 to December 2013 , 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs . The study design consisted of three consecutive cohorts ( six patients each ) with dose escalation : low dose ( 2 × 10(6 ) cells ) , medium dose ( 10 × 10(6 ) ) , and high dose ( 50 × 10(6 ) ) . The primary outcome parameter was safety evaluated by recording adverse events throughout the trial , and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index . After 6 months of follow-up , the procedure was found to be safe , and no serious adverse events were reported . Four patients experienced transient knee joint pain and swelling after local injection . Interestingly , patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline . Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients . A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy . SIGNIFICANCE Although this phase I study included a limited number of patients without a placebo arm , it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis . This study also provides encouraging preliminary evidence of efficacy . Larger and controlled long-term studies are now m and atory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis Mesenchymal stem cells ( MSCs ) are known to have a potential for articular cartilage regeneration . However , most studies focused on focal cartilage defect through surgical implantation . For the treatment of generalized cartilage loss in osteoarthritis , an alternative delivery strategy would be more appropriate . The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs ( AD-MSCs ) for knee osteoarthritis  . We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee . The phase I study consists of three dose-escalation cohorts ; the low-dose ( 1.0 × 10(7 ) cells ) , mid-dose ( 5.0 × 10(7 ) ) , and high-dose ( 1.0 × 10(8 ) ) group with three patients each . The phase II included nine patients receiving the high-dose . The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index ( WOMAC ) at 6 months . Secondary outcomes included clinical , radiological , arthroscopic , and histological evaluations . There was no treatment-related adverse event . The WOMAC score improved at 6 months after injection in the high-dose group . The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group . Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group . Histology demonstrated thick , hyaline-like cartilage regeneration . These results showed that intra-articular injection of 1.0 × 10(8 ) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events , and reduced cartilage defects by regener 
    Output:
    
agent
***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: PURPOSE This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy ( HTO ) for varus deformity , with or without mesenchymal stem cell ( MSC ) therapy .  METHODS This prospect i ve , comparative observational study was design ed to evaluate the effectiveness of MSC therapy . The patients were divided into 2 groups : HTO with platelet-rich plasma ( PRP ) injection only ( n = 23 ) or HTO in conjunction with MSC therapy and PRP injection ( n = 21 ) . Prospect i ve evaluations of both groups were performed using the Lysholm score , Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , and a visual analog scale ( VAS ) score for pain . Second-look arthroscopy was carried out in all patients at the time of metal removal . RESULTS The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain ( PRP only , 74.0 ± 5.7 ; MSC-PRP , 81.2 ± 6.9 ; P < .001 ) and symptoms ( PRP only , 75.4 ± 8.5 ; MSC-PRP , 82.8 ± 7.2 ; P = .006 ) relative to the PRP-only group . Although the mean Lysholm score was similarly improved in both groups ( PRP only , 80.6 ± 13.5 ; MSC-PRP , 84.7 ± 16.2 ; P = .357 ) , the MSC-PRP group showed a significantly greater improvement in the VAS pain score  ( PRP only , 16.2 ± 4.6 ; MSC-PRP , 10.2 ± 5.7 ; P < .001 ) . There were no differences in the preoperative ( PRP only , varus 2.8 ° ± 1.7 ° ; MSC-PRP , varus 3.4 ° ± 3.0 ° ; P = .719 ) and postoperative ( PRP only , valgus 9.8 ° ± 2.4 ° ; MSC-PRP , valgus 8.7 ° ± 2.3 ° ; P = .678 ) femorotibial angles or weight-bearing lines between the groups . Arthroscopic evaluation , at plate removal , showed that partial or even fibrocartilage coverage was achieved in 50 % of the MSC-PRP group patients but in only 10 % of the patients in the PRP-only group ( P < .001 ) . CONCLUSIONS MSC therapy , in conjunction with HTO , mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Introduction Knee osteoarthritis ( OA ) is the most common articular disease . Different methods are used to alleviate the symptoms of patients with knee OA , including analgesics , physical therapy , exercise prescription , and intra-articular injections ( glucocorticoids , hyaluronic acid [ HA ] , etc ) . New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage , including the use of platelet-rich plasma ( PRP ) as a complex of growth factors . Due to the high incidence of OA and its consequences , we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA . Method This non-placebo-controlled r and omized clinical trial involved 160 patients affected by knee OA , grade 1–4 of Kellgren – Lawrence scale . In the PRP group ( n = 87 ) , two intra-articular injections at 4-week interval were applied , and in the HA group ( n = 73 ) , three doses of intra-articular injection at 1-week interval were applied . All patients were prospect ively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) and SF-36 question naires . The results were analyzed using SPSS 16.1 software ( RCT code : I RCT 2014012113442N5 ) . Results At the 12-month follow-up , WOMAC pain score and bodily pain significantly improved in both groups ; however , better results were determined in the PRP group compared to the HA group ( P < 0.001 ) . Other WOMAC and SF-36 parameters improved only in the PRP group . More improvement ( but not statistically significant ) was achieved in patients with grade 2 OA in both the groups . Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment Purpose To assess the outcome of intra-articular platelet-rich plasma ( PRP ) injections into the knee in patients with early stages of osteoarthritis ( OA ) and to determine whether cyclical dosing would affect the end result . Methods This is a prospect i ve , r and omized study in which 93 patients ( 119 knees ) were followed up for a minimum of 2 years . Fifty knees were r and omly selected prior to the first injection , to receive a second cycle at the completion of 1 year . A cycle consisted of three injections , each given at a monthly interval . The outcome was assessed using Knee Injury and Osteoarthritis Outcome Score ( KOOS ) , Visual Analogue Scale ( VAS ) , Tegner and Marx scoring systems , recorded prior to the first injection and then at 12 , 18 and 24 months . Results There was a significant improvement in all scores over time compared to the pre-treatment value ( p < 0.001 ) . At 12 months , both groups showed similar and significant improvement . At 18 months , except for KOOS ( Symptoms ) and Tegner score , all other parameters showed a significant difference between the two groups in favour of the patients who had received the second cycle ( p < 0.001 ) . At 2 years , the scores declined in both groups but remained above the pre-treatment value with no significant difference between the groups despite the patients with two cycles showing higher mean values for all the scores . Conclusion Intra-articular PRP injections into the knee for symptomatic early stages of OA are a valid treatment option . There is a significant reduction in pain and improvement in function after 12 months , which can be further improved at 18 months by annual repetition of the treatment . Although the beneficial effects are ill sustained at 2 years , the results are encouraging when compared to the pre-treatment function . Level of evidence II We design ed a r and omized clinical trial with control group , to investigate the effects of platelet rich plasma ( PRP ) on pain , stiffness , function and quality of life in patients with knee osteoarthritis . Patients were r and omly divided in two groups . For both groups of participants , therapeutic exercise was prescribed . In the PRP group , two courses of leukocyte rich PRP ( 5.6 fold higher platelet concentration ) with a 4-week interval was injected . For each participant , Western Ontario and McMaster University ’s Arthritis Index ( WOMAC ) and the SF-36 question naire ( Farsi version ) were filled at the baseline and 6 months after treatments . Thirty-one patients in the PRP group and 31 patients in the control group were studied .  Mean changes of total WOMAC , physical component summery and mental component summery of Short Form-36 in PRP group showed better improvement than control group ( P<0.05 ) . This study showed that intra articular PRP knee injection combined with therapeutic exercise can be more effective in pain reduction and improvement of stiffness and quality of life , compared with therapeutic exercise alone Purpose This study was performed to compare the efficacy of treatment in three groups of patients with knee osteoarthritis ( OA ) given an intra-articular injection of platelet-rich plasma ( PRP ) , hyaluronic acid ( HA ) or ozone gas . Methods A total of 102 patients with mild – moderate and moderate knee OA who presented at the polyclinic with at least a 1-year history of knee pain and VAS score ≥4 were r and omly separated into three groups . Group 1 ( PRP group ) received intra-articular injection of PRP × 2 doses , Group 2 ( HA group ) received a single dose of HA , and Group 3 ( Ozone group ) received ozone × four doses . Weight-bearing anteroposterior – lateral and Merchant ’s radiographs of both knees were evaluated . WOMAC and VAS scores were applied to all patients on first presentation and at 1 , 3 , 6 and 12 months . Results At the end of the 1st month after injection , significant improvements were seen in all groups . In the 3rd month , the improvements in WOMAC and VAS scores were similar in Groups 1 and 2 , while those in Group 3 were lower ( p < 0.001 ) . At the 6th month , while the clinical efficacies  of PRP and HA were similar and continued , the clinical effect of ozone had disappeared ( p < 0.001 ) . At the end of the 12th month , PRP was determined to be both statistically and clinical ly superior to HA ( p < 0.001 ) . Conclusion In the treatment of mild – moderate knee OA , PRP was more successful than HA and ozone injections , as the application alone was sufficient to provide at least 12 months of pain-free daily living activities . Level of evidence Therapeutic study , Level UNLABELLED : Osteoarthritis ( OA ) is the most widespread musculoskeletal disorder in adults . It leads to cartilage damage associated with subchondral bone changes and synovial inflammation , causing pain and disability . The present study aim ed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells ( ASCs ) in patients with knee OA , as well as clinical efficacy as secondary endpoint . A bicentric , uncontrolled , open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries . From April 2012 to December 2013 , 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs . The study design consisted of three consecutive cohorts ( six patients each ) with dose escalation : low dose ( 2 × 10(6 ) cells ) , medium dose ( 10 × 10(6 ) ) , and high dose ( 50 × 10(6 ) ) . The primary outcome parameter was safety evaluated by recording adverse events throughout the trial , and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index . After 6 months of follow-up , the procedure was found to be safe , and no serious adverse events were reported . Four patients experienced transient knee joint pain and swelling after local injection . Interestingly , patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline . Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients . A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy . SIGNIFICANCE Although this phase I study included a limited number of patients without a placebo arm , it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis . This study also provides encouraging preliminary evidence of efficacy . Larger and controlled long-term studies are now m and atory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis Mesenchymal stem cells ( MSCs ) are known to have a potential for articular cartilage regeneration . However , most studies focused on focal cartilage defect through surgical implantation . For the treatment of generalized cartilage loss in osteoarthritis , an alternative delivery strategy would be more appropriate . The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs ( AD-MSCs ) for knee osteoarthritis  . We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee . The phase I study consists of three dose-escalation cohorts ; the low-dose ( 1.0 × 10(7 ) cells ) , mid-dose ( 5.0 × 10(7 ) ) , and high-dose ( 1.0 × 10(8 ) ) group with three patients each . The phase II included nine patients receiving the high-dose . The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index ( WOMAC ) at 6 months . Secondary outcomes included clinical , radiological , arthroscopic , and histological evaluations . There was no treatment-related adverse event . The WOMAC score improved at 6 months after injection in the high-dose group . The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group . Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group . Histology demonstrated thick , hyaline-like cartilage regeneration . These results showed that intra-articular injection of 1.0 × 10(8 ) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events , and reduced cartilage defects by regener 
    Output:
    