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: Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for  chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality Purpose To compare the effectiveness and safety of intra-articular injections of autologous exp and ed mesenchymal stromal stem cells alone ( MSCs ) , or in combination with platelet-rich plasma ( MSCs + PRP ) , in patients with knee osteoarthritis . Methods Eighteen patients ( 57.6 ± 9.6 years ) with radiographic symptomatic knee osteoarthritis ( Dejour grade s II – IV ) were r and omized to receive intra-articular injections of MSCs ( n = 9 ) or MSCs + PRP ( n = 9 ) . Injections were performed 2–3 weeks after bone marrow aspiration ( ± 80–100 ml ) which was obtained from both posterior iliac crests . Results The Knee Injury and Osteoarthritis Outcome Score ( KOOS ) improved significantly throughout the 12 months for both groups ( p < 0.05 ) . No statistically significant differences between groups were found in KOOS subscales and global score improvements at 12-month end-point ( n.s . ) . The MSCs group showed significant improvements in the pain , function and daily living activities , and sports and recreational activities subscales ( p < 0.05 ) . Similarly , the MSCs + PRP group showed significant improvements in the pain , function and daily living activities and quality of life subscales ( p < 0.05 ) . The average number of fibroblast colony forming units ( CFU-F ) was 56.8 + 21.9 for MSCs group and 50.7 ± 21.7 for MSCs + PRP group . Minimal adverse effects were seen in both groups ( 10 adverse events , in 5 patients ) . Conclusions Intra-articular injections of exp and ed MSCs alone or in combination with PRP are safe and have a beneficial effect on symptoms in patients with symptomatic knee osteoarthritis . Adding PRP to the MSCs injections did not provide additional benefit . These results are encouraging and support the recommendation of this minimally invasive procedure in patients with knee osteoarthritis , without requiring hospitalization . The CFU-F results may be used as reference for future research .Level of evidence Prospect i ve cohort study , Level II 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 Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of  chronic knee osteoarthritis  that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality Abstract Purpose Well balanced knees with good alignment are essential for a well-functioning TKA with long survival of its implants . This prospect i ve r and omized study comparing navigation-assisted TKA and conventional TKA reported the clinical and radiological outcomes at a follow-up of 9 years . The purpose of this study was to compare the clinical and radiological outcomes for patients who underwent navigation-assisted TKA or conventional TKA after long-term follow-up . Methods A total of 80 patients ( 88 knees ) were available for physical and radiological examination 9 years after TKA . Clinical outcomes were evaluated using HSS , WOMAC , and KS function and pain scores . And radiological outcomes of the component loosening and its survivorship during 9-year follow-up were also evaluated . Results There were no significant differences in the field of clinical outcomes between the two groups . In terms of radiological outcomes , the navigation group had fewer alignment outliers ( 7.3 vs 20 % , p = 0.006 ) . Although the clinical outcomes showed no differences between the two groups , the survival rate was slightly better in the navigation group than in the conventional group without statistical significance ( best-case scenario 100 vs 95.3 % , n.s . , worst-case scenario 95.6 vs 88.4 % , n.s . ) . Conclusion Navigation-assisted TKA produced better alignment outcomes and better survival rates than conventional instruments although some of the differences were not statistically significant . Level of evidence BACKGROUND This safety and feasibility study used autologous adipose-derived stromal vascular cells ( the stromal vascular fraction [ SVF ] of adipose tissue ) , to treat 8 osteoarthritic knees in 6 patients of grade I to III ( K-L scale ) with initial pain of 4 or greater on a 10-point Visual Analog Scale ( VAS ) . OBJECTIVES The primary objective of the study was evaluation of the safety of intra-articular injection of SVF .  The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees . METHODS Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate , resuspension in 3 mL of Lactated Ringer 's Solution , and injection directly into the intra-articular space of the knee , with a mean of 14.1 million viable , nucleated SVF cells per knee . Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , the VAS pain scale , range of motion ( ROM ) , timed up- and -go ( TUG ) , and MRI . RESULTS No infections , acute pain flares , or other adverse events were reported . At 3-months postoperative , there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001 , respectively ) , which was maintained at 1 year . Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative . St and ard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences . All patients attained full activity with decreased knee pain . CONCLUSIONS Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee . LEVEL OF EVIDENCE 4 : Therapeutic Abstract Background Mesenchymal stromal cells are a promising option to treat  knee osteoarthritis . Their safety and usefulness must be confirmed and the optimal dose established . We tested increasing doses of bone marrow mesenchymal stromal cells ( BM-MSCs ) in combination with hyaluronic acid in a r and omized clinical trial . Material sA phase I/II multicenter r and omized clinical trial with active control was conducted . Thirty patients diagnosed with knee OA were r and omly assigned to intraarticularly administered hyaluronic acid alone ( control ) , or together with 10 × 106 or 100 × 106 cultured autologous BM-MSCs , and followed up for 12 months . Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range . X-ray and magnetic resonance imaging analyses were performed to analyze joint damage . Results No adverse effects were reported after BM-MSC administration or during follow-up . BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value ( IQR ) for control , low-dose and high-dose groups change from 5 ( 3 , 7 ) , 7 ( 5 , 8) and 6 ( 4 , 8) to 4 ( 3 , 5 ) , 2 ( 1 , 3 ) and 2 ( 0,4 ) respectively at 12 months ( low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009 ) . BM-MSC-administered patients were also superior according to WOMAC , although improvement in control and low-dose patients could not be significantly sustained beyond 6 months . On the other h and , the BM-MSC high-dose group exhibited an improvement of 16.5 ( 12 , 19 ) points at 12 months ( p < 0.01 ) . Consistent with WOMAC and VAS values , motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs . X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group . MRI ( WORMS protocol ) showed that joint damage decreased only in the BM-MSC high-dose group , albeit slightly . Conclusions The single intraarticular injection of in vitro exp and ed autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA , especially when 100 ×  
    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: Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for  chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality Purpose To compare the effectiveness and safety of intra-articular injections of autologous exp and ed mesenchymal stromal stem cells alone ( MSCs ) , or in combination with platelet-rich plasma ( MSCs + PRP ) , in patients with knee osteoarthritis . Methods Eighteen patients ( 57.6 ± 9.6 years ) with radiographic symptomatic knee osteoarthritis ( Dejour grade s II – IV ) were r and omized to receive intra-articular injections of MSCs ( n = 9 ) or MSCs + PRP ( n = 9 ) . Injections were performed 2–3 weeks after bone marrow aspiration ( ± 80–100 ml ) which was obtained from both posterior iliac crests . Results The Knee Injury and Osteoarthritis Outcome Score ( KOOS ) improved significantly throughout the 12 months for both groups ( p < 0.05 ) . No statistically significant differences between groups were found in KOOS subscales and global score improvements at 12-month end-point ( n.s . ) . The MSCs group showed significant improvements in the pain , function and daily living activities , and sports and recreational activities subscales ( p < 0.05 ) . Similarly , the MSCs + PRP group showed significant improvements in the pain , function and daily living activities and quality of life subscales ( p < 0.05 ) . The average number of fibroblast colony forming units ( CFU-F ) was 56.8 + 21.9 for MSCs group and 50.7 ± 21.7 for MSCs + PRP group . Minimal adverse effects were seen in both groups ( 10 adverse events , in 5 patients ) . Conclusions Intra-articular injections of exp and ed MSCs alone or in combination with PRP are safe and have a beneficial effect on symptoms in patients with symptomatic knee osteoarthritis . Adding PRP to the MSCs injections did not provide additional benefit . These results are encouraging and support the recommendation of this minimally invasive procedure in patients with knee osteoarthritis , without requiring hospitalization . The CFU-F results may be used as reference for future research .Level of evidence Prospect i ve cohort study , Level II 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 Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of  chronic knee osteoarthritis  that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality Abstract Purpose Well balanced knees with good alignment are essential for a well-functioning TKA with long survival of its implants . This prospect i ve r and omized study comparing navigation-assisted TKA and conventional TKA reported the clinical and radiological outcomes at a follow-up of 9 years . The purpose of this study was to compare the clinical and radiological outcomes for patients who underwent navigation-assisted TKA or conventional TKA after long-term follow-up . Methods A total of 80 patients ( 88 knees ) were available for physical and radiological examination 9 years after TKA . Clinical outcomes were evaluated using HSS , WOMAC , and KS function and pain scores . And radiological outcomes of the component loosening and its survivorship during 9-year follow-up were also evaluated . Results There were no significant differences in the field of clinical outcomes between the two groups . In terms of radiological outcomes , the navigation group had fewer alignment outliers ( 7.3 vs 20 % , p = 0.006 ) . Although the clinical outcomes showed no differences between the two groups , the survival rate was slightly better in the navigation group than in the conventional group without statistical significance ( best-case scenario 100 vs 95.3 % , n.s . , worst-case scenario 95.6 vs 88.4 % , n.s . ) . Conclusion Navigation-assisted TKA produced better alignment outcomes and better survival rates than conventional instruments although some of the differences were not statistically significant . Level of evidence BACKGROUND This safety and feasibility study used autologous adipose-derived stromal vascular cells ( the stromal vascular fraction [ SVF ] of adipose tissue ) , to treat 8 osteoarthritic knees in 6 patients of grade I to III ( K-L scale ) with initial pain of 4 or greater on a 10-point Visual Analog Scale ( VAS ) . OBJECTIVES The primary objective of the study was evaluation of the safety of intra-articular injection of SVF .  The secondary objective was to assess initial feasibility for reduction of pain in osteoarthritic knees . METHODS Adipose-derived SVF cells were obtained through enzymatic disaggregation of lipoaspirate , resuspension in 3 mL of Lactated Ringer 's Solution , and injection directly into the intra-articular space of the knee , with a mean of 14.1 million viable , nucleated SVF cells per knee . Metrics included monitoring of adverse events and preoperative to postoperative changes in the Western Ontario and McMaster Universities Arthritis Index ( WOMAC ) , the VAS pain scale , range of motion ( ROM ) , timed up- and -go ( TUG ) , and MRI . RESULTS No infections , acute pain flares , or other adverse events were reported . At 3-months postoperative , there was a statistically significant improvement in WOMAC and VAS scores ( P < .02 and P < .001 , respectively ) , which was maintained at 1 year . Physical therapy measurements for ROM and TUG both improved from preoperative to 3-months postoperative . St and ard MRI assessment from preoperative to 3-months postoperative showed no detectable structural differences . All patients attained full activity with decreased knee pain . CONCLUSIONS Autologous SVF was shown to be safe and to present a new potential therapy for reduction of pain for osteoarthritis of the knee . LEVEL OF EVIDENCE 4 : Therapeutic Abstract Background Mesenchymal stromal cells are a promising option to treat  knee osteoarthritis . Their safety and usefulness must be confirmed and the optimal dose established . We tested increasing doses of bone marrow mesenchymal stromal cells ( BM-MSCs ) in combination with hyaluronic acid in a r and omized clinical trial . Material sA phase I/II multicenter r and omized clinical trial with active control was conducted . Thirty patients diagnosed with knee OA were r and omly assigned to intraarticularly administered hyaluronic acid alone ( control ) , or together with 10 × 106 or 100 × 106 cultured autologous BM-MSCs , and followed up for 12 months . Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range . X-ray and magnetic resonance imaging analyses were performed to analyze joint damage . Results No adverse effects were reported after BM-MSC administration or during follow-up . BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value ( IQR ) for control , low-dose and high-dose groups change from 5 ( 3 , 7 ) , 7 ( 5 , 8) and 6 ( 4 , 8) to 4 ( 3 , 5 ) , 2 ( 1 , 3 ) and 2 ( 0,4 ) respectively at 12 months ( low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009 ) . BM-MSC-administered patients were also superior according to WOMAC , although improvement in control and low-dose patients could not be significantly sustained beyond 6 months . On the other h and , the BM-MSC high-dose group exhibited an improvement of 16.5 ( 12 , 19 ) points at 12 months ( p < 0.01 ) . Consistent with WOMAC and VAS values , motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs . X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group . MRI ( WORMS protocol ) showed that joint damage decreased only in the BM-MSC high-dose group , albeit slightly . Conclusions The single intraarticular injection of in vitro exp and ed autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA , especially when 100 ×  
    Output:
    