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 In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment . There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease : some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement ( TKR ) ; whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement ( UKR ) . Both interventions are established and well-documented procedures . Little evidence exists to prove the clinical and cost-effectiveness of either management option . This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology . The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis . Methods / Design The design of the study is a single layer multicentre superiority type r and omised controlled trial of unilateral knee replacement patients . Blinding will not be possible as the surgical scars for each procedure differ . We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals . Participants will be r and omised to either UKR or TKR . R and omisation will occur using a web-based r and omisation system . The study is pragmatic in terms of implant selection for the knee replacement operation . Participants will be followed up for 5 years . The primary outcome is the Oxford Knee Score , which will be collected via question naires at 2 months , 1 year and then annually to 5 years . Secondary outcomes will include cost-effectiveness , patient satisfaction and complications data .Trial registration Current Controlled Trials IS RCT N03013488 ; Clinical Trials.gov Identifier : Background : Autologous chondrocyte implantation ( ACI ) has been shown to be effective in the midterm for the treatment of symptomatic articular cartilage lesions of the knee , but few long-term series have been published . The multioperated chronic articular cartilage defect remains a difficult condition to treat . Purpose : To examine the long-term clinical results of ACI for large chronic articular cartilage defects , many treated as salvage . Study Design : Case series ; Level of evidence , 4 . Methods : This is a prospect i ve case series of 104 patients with a mean age of 30.2 years and a symptomatic lesion of the articular cartilage in the knee , who underwent ACI between 1998 and 2001 . The mean duration of symptoms before surgery was 7.8 years . The mean number of previous surgical procedures on the cartilage defect , excluding arthroscopic debridement , was 1.3 . The defects were large , with a mean size of 477.1 mm2 ( range , 120 - 2500 mm2 ) . The modified Cincinnati , Stanmore/Bentley , and visual analog scale for pain scoring systems were used to assess pain and functional outcomes at a minimum 10 years ( mean , 10.4 years ; range , 10 - 12 years ) . Results : Twenty-seven patients ( 26 % ) experienced graft failure at a mean of 5.7 years after ACI . Of the 73 patients who did not fail , 46 patients ( 63 % of patients with a surviving graft ) had an excellent result , 18 ( 25 % ) were good , 6 ( 8 % ) were fair , and 3 ( 4 % ) had a poor result . Of a total of 100 patients successfully followed up , 98 were satisfied with the ACI technique for their chronic knee pain and would undergo the procedure again . Conclusion : Autologous chondrocyte implantation can provide a long-term solution in more than 70 % of young patients of a difficult-to-treat group with large chronic articular cartilage lesions , even in the salvage situation Background : There are currently several approaches being pursued to treat focal defects of articular cartilage , each having specific advantages or challenges . A single-stage procedure that uses autologous cartilage fragments , Cartilage Autograft Implantation System ( CAIS ) , is being evaluated in patients and may offer a clinical ly effective option . Purpose : To establish the safety of CAIS and to test whether CAIS improves quality of life by using st and ardized outcomes assessment tools . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : Patients ( n = 29 ) were r and omized ( 1:2 ) with the intent to treat with either a  control ( microfracture [ MFX ] ) or an experimental ( CAIS ) procedure . Patients were followed at predetermined time points for 2 years using several st and ardized outcomes assessment tools ( SF-36 , International Knee Documentation Committee [ IKDC ] , Knee injury and Osteoarthritis Outcome Score [ KOOS ] ) . Magnetic resonance imaging was performed at baseline , 3 weeks , and 6 , 12 , and 24 months . Results : Lesion size and International Cartilage Repair Society ( ICRS ) grade were similar in both groups . General outcome measures ( eg , physical component score of the SF-36 ) indicated an overall improvement in both groups , and no differences in the number of adverse effects were noted in comparisons between the CAIS and MFX groups . The IKDC score of the CAIS group was significantly higher ( 73.9 ± 14.72 at 12 months and 82.95 ± 14.88 at 24 months ) compared with the MFX group ( 57.78 ± 18.31 at 12 months and 59.5 ± 13.44 at 24 months ) . Select subdomains ( 4/5 ) in the KOOS instrument were significantly different at 12 and 18 months , and all subdomains ( Symptoms and Stiffness , Pain , Activities of Daily Living , Sports and Recreation , Knee-related Quality of Life ) were significantly increased at 24 months in CAIS with scores of 88.47 ± 11.68 , 90.64 ± 7.87 , 97.29 ± 3.8 , 78.16 ± 22.06 , and 69 ± 23.15 compared with 75 ± 9.31 , 78.94 ± 13.73 , 89.46 ± 8.13 , 51.67 ± 26.01 , and 37.15 ± 21.67 in the MFX group . These significant improvements were maintained at 24 months in both IKDC and KOOS . Qualitative analysis of the imaging data did not note differences between the 2 groups in fill of the graft bed , tissue integration , or presence of subchondral cysts . Patients treated with MFX had a significantly higher incidence of intralesional osteophyte formation ( 54 % and 70 % of total number of lesions treated ) at 6 and 12 months when compared with CAIS ( 8 % and 25 % of total number of lesions treated ) . Conclusion : The first clinical experience in using CAIS for treating patients with focal chondral defects indicates that it is a safe , feasible , and effective method that may improve long-term clinical outcomes Background Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects . Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation . Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate . Study Design Cohort study ; Level of evidence , 2 . Methods The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospect ively collected data . Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique . Outcomes were classified as complete failure if more than 25 % of a grafted defect area had to be removed in later procedures because of persistent symptoms . Results There were 522 defects in 321 patients ( 325 joints ) treated with autologous chondrocyte implantation .  On average , there were 1.7 lesions per patient . Of these joints , 111 had previously undergone surgery that penetrated the subchondral bone ; 214 joints had no prior treatment that affected the subchondral bone and served as controls . Within the marrow stimulation group , there were 29 ( 26 % ) failures , compared with 17 ( 8 % ) failures in the control group . Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of nontreated defects . The failure rates for drilling ( 28 % ) , abrasion arthroplasty ( 27 % ) , and microfracture ( 20 % ) were not significantly different , possibly because of the lower number of microfracture patients in this cohort ( 25 of 110 marrow-stimulation procedures ) . The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and therefore should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation Abstract Background : Knee cartilage lesions increase the risk of developing osteoarthritis ( OA ) , and may eventually result in a total knee replacement ( TKR ) . There is currently no consensus on the optimal treatment of cartilage lesions . ChondroCelect ® ( CC ) is a cell-based therapy approved for use in autologous chondrocytes implantation ( ACI ) to treat symptomatic cartilage defects of the femoral condyle . Its capacity to safely restore good- quality cartilage was demonstrated in a r and omized controlled trial ( RCT ) versus the surgical procedure microfracture ( MFX ) . Objective : This study investigated the cost utility of CC used in ACI compared with MFX to treat symptomatic knee cartilage lesions in Belgium . Methods : A decision tree model comparing CC with MFX over a 40-year horizon was developed in TreeAge Pro ™ . The key timepoints of the model were ( i ) clinical assessment 5 years after initial intervention ( success or no success , with or without re-operation ) ; ( ii ) development of OA at 15 years ( yes/no ) ; ( iii ) need for TKR at 20 years ( yes/no ) ; and ( iv ) need for prosthesis revision at 35 years ( yes/no ) . Clinical data provided by the RCT of CC versus MFX were the clinical success ( response ) rate based on the Knee injury and Osteoarthritis Outcome Score ( KOOS ) at 36 months ( 82.9 % vs 62.0 % ; p = 0.048 ) and the proportion of good structural repair/presence of hyaline cartilage based on International Cartilage Repair Society ( ICRS II ) visual item at 12 months ( 44.9 % vs 23.2 % ; p= 0.023 ) . Utility scores by surgery outcome were derived from the SF-36 question naire responses collected in the RCT . Conservative assumptions related to the incidences of OA , TKR and prosthesis revision relied on a literature search . A patient chart review ( n = 82 ) provided follow-up costs by surgery outcome . National tariffs were applied to direct medical re sources used ( healthcare payer perspective , year 2008 costs ) . Annual discounting was applied to costs ( 3 % ) and effects ( 1.5 % ) as recommended by the Belgian pharmacoeconomic guidelines . Results : The incremental cost per QALY gained for CC compared with MFX was € 16 229 , with a difference in costs of € 20 802 and 1.282 QALYs gained . Sensitivity analyses indicated that the key model drivers were the proportion of patients with hyaline cartilage and the correlation between hyaline cartilage formation and later avoidance of OA . Probabilistic sensitivity analyses showed robustness of the results , with 80 % of the simulations below the usual UK National Institute for Health and Clinical Excellence ( NICE ) threshold of € 22 000 per QALY . Conclusions : Assuming a good correlation between high- quality cartilage repair and avoidance of OA at a later stage , the benefits of the cell therapy CC over MFX in terms of QALYs gained and OA-related costs avoided appear real . Further research is required to explore long-term effects of cartilage repair and reduce uncertainty on quality of life of patients with OA before and after joint replacement BACKGROUND Despite introduction of autologous chondrocyte therapy for repair of hyaline articular cartilage injury in 1994 , microfracture remains a primary st and ard of care . NeoCart , an autologous cartilage tissue implant , was compared with microfracture in a multisite prospect i ve , r and omized trial of a tissue-engineered bioimplant for treating articular cartilage injuries in the knee . METHODS Thirty patients were r and omized at a ratio of two to one ( two were treated with an autologous cartilage tissue implant [ NeoCart ] for each patient treated with microfracture )  at the time of arthroscopic confirmation of an International Cartilage Repair Society ( ICRS ) grade -III lesion(s ) . Microfracture or cartilage biopsy was performed . NeoCart , produced by seeding a type-I collagen matrix scaffold with autogenous chondrocytes and bioreactor treatment , was implanted six weeks following arthroscopic cartilage biopsy . St and ard evaluations were performed with vali date d clinical outcomes measures . RESULTS Three , six , twelve , and twenty-four- 
    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 In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment . There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease : some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement ( TKR ) ; whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement ( UKR ) . Both interventions are established and well-documented procedures . Little evidence exists to prove the clinical and cost-effectiveness of either management option . This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology . The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis . Methods / Design The design of the study is a single layer multicentre superiority type r and omised controlled trial of unilateral knee replacement patients . Blinding will not be possible as the surgical scars for each procedure differ . We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals . Participants will be r and omised to either UKR or TKR . R and omisation will occur using a web-based r and omisation system . The study is pragmatic in terms of implant selection for the knee replacement operation . Participants will be followed up for 5 years . The primary outcome is the Oxford Knee Score , which will be collected via question naires at 2 months , 1 year and then annually to 5 years . Secondary outcomes will include cost-effectiveness , patient satisfaction and complications data .Trial registration Current Controlled Trials IS RCT N03013488 ; Clinical Trials.gov Identifier : Background : Autologous chondrocyte implantation ( ACI ) has been shown to be effective in the midterm for the treatment of symptomatic articular cartilage lesions of the knee , but few long-term series have been published . The multioperated chronic articular cartilage defect remains a difficult condition to treat . Purpose : To examine the long-term clinical results of ACI for large chronic articular cartilage defects , many treated as salvage . Study Design : Case series ; Level of evidence , 4 . Methods : This is a prospect i ve case series of 104 patients with a mean age of 30.2 years and a symptomatic lesion of the articular cartilage in the knee , who underwent ACI between 1998 and 2001 . The mean duration of symptoms before surgery was 7.8 years . The mean number of previous surgical procedures on the cartilage defect , excluding arthroscopic debridement , was 1.3 . The defects were large , with a mean size of 477.1 mm2 ( range , 120 - 2500 mm2 ) . The modified Cincinnati , Stanmore/Bentley , and visual analog scale for pain scoring systems were used to assess pain and functional outcomes at a minimum 10 years ( mean , 10.4 years ; range , 10 - 12 years ) . Results : Twenty-seven patients ( 26 % ) experienced graft failure at a mean of 5.7 years after ACI . Of the 73 patients who did not fail , 46 patients ( 63 % of patients with a surviving graft ) had an excellent result , 18 ( 25 % ) were good , 6 ( 8 % ) were fair , and 3 ( 4 % ) had a poor result . Of a total of 100 patients successfully followed up , 98 were satisfied with the ACI technique for their chronic knee pain and would undergo the procedure again . Conclusion : Autologous chondrocyte implantation can provide a long-term solution in more than 70 % of young patients of a difficult-to-treat group with large chronic articular cartilage lesions , even in the salvage situation Background : There are currently several approaches being pursued to treat focal defects of articular cartilage , each having specific advantages or challenges . A single-stage procedure that uses autologous cartilage fragments , Cartilage Autograft Implantation System ( CAIS ) , is being evaluated in patients and may offer a clinical ly effective option . Purpose : To establish the safety of CAIS and to test whether CAIS improves quality of life by using st and ardized outcomes assessment tools . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : Patients ( n = 29 ) were r and omized ( 1:2 ) with the intent to treat with either a  control ( microfracture [ MFX ] ) or an experimental ( CAIS ) procedure . Patients were followed at predetermined time points for 2 years using several st and ardized outcomes assessment tools ( SF-36 , International Knee Documentation Committee [ IKDC ] , Knee injury and Osteoarthritis Outcome Score [ KOOS ] ) . Magnetic resonance imaging was performed at baseline , 3 weeks , and 6 , 12 , and 24 months . Results : Lesion size and International Cartilage Repair Society ( ICRS ) grade were similar in both groups . General outcome measures ( eg , physical component score of the SF-36 ) indicated an overall improvement in both groups , and no differences in the number of adverse effects were noted in comparisons between the CAIS and MFX groups . The IKDC score of the CAIS group was significantly higher ( 73.9 ± 14.72 at 12 months and 82.95 ± 14.88 at 24 months ) compared with the MFX group ( 57.78 ± 18.31 at 12 months and 59.5 ± 13.44 at 24 months ) . Select subdomains ( 4/5 ) in the KOOS instrument were significantly different at 12 and 18 months , and all subdomains ( Symptoms and Stiffness , Pain , Activities of Daily Living , Sports and Recreation , Knee-related Quality of Life ) were significantly increased at 24 months in CAIS with scores of 88.47 ± 11.68 , 90.64 ± 7.87 , 97.29 ± 3.8 , 78.16 ± 22.06 , and 69 ± 23.15 compared with 75 ± 9.31 , 78.94 ± 13.73 , 89.46 ± 8.13 , 51.67 ± 26.01 , and 37.15 ± 21.67 in the MFX group . These significant improvements were maintained at 24 months in both IKDC and KOOS . Qualitative analysis of the imaging data did not note differences between the 2 groups in fill of the graft bed , tissue integration , or presence of subchondral cysts . Patients treated with MFX had a significantly higher incidence of intralesional osteophyte formation ( 54 % and 70 % of total number of lesions treated ) at 6 and 12 months when compared with CAIS ( 8 % and 25 % of total number of lesions treated ) . Conclusion : The first clinical experience in using CAIS for treating patients with focal chondral defects indicates that it is a safe , feasible , and effective method that may improve long-term clinical outcomes Background Marrow stimulation techniques such as drilling or microfracture are first-line treatment options for symptomatic cartilage defects . Common knowledge holds that these treatments do not compromise subsequent cartilage repair procedures with autologous chondrocyte implantation . Hypothesis Cartilage defects pretreated with marrow stimulation techniques will have an increased failure rate . Study Design Cohort study ; Level of evidence , 2 . Methods The first 321 consecutive patients treated at one institution with autologous chondrocyte implantation for full-thickness cartilage defects that reached more than 2 years of follow-up were evaluated by prospect ively collected data . Patients were grouped based on whether they had undergone prior treatment with a marrow stimulation technique . Outcomes were classified as complete failure if more than 25 % of a grafted defect area had to be removed in later procedures because of persistent symptoms . Results There were 522 defects in 321 patients ( 325 joints ) treated with autologous chondrocyte implantation .  On average , there were 1.7 lesions per patient . Of these joints , 111 had previously undergone surgery that penetrated the subchondral bone ; 214 joints had no prior treatment that affected the subchondral bone and served as controls . Within the marrow stimulation group , there were 29 ( 26 % ) failures , compared with 17 ( 8 % ) failures in the control group . Conclusion Defects that had prior treatment affecting the subchondral bone failed at a rate 3 times that of nontreated defects . The failure rates for drilling ( 28 % ) , abrasion arthroplasty ( 27 % ) , and microfracture ( 20 % ) were not significantly different , possibly because of the lower number of microfracture patients in this cohort ( 25 of 110 marrow-stimulation procedures ) . The data demonstrate that marrow stimulation techniques have a strong negative effect on subsequent cartilage repair with autologous chondrocyte implantation and therefore should be used judiciously in larger cartilage defects that could require future treatment with autologous chondrocyte implantation Abstract Background : Knee cartilage lesions increase the risk of developing osteoarthritis ( OA ) , and may eventually result in a total knee replacement ( TKR ) . There is currently no consensus on the optimal treatment of cartilage lesions . ChondroCelect ® ( CC ) is a cell-based therapy approved for use in autologous chondrocytes implantation ( ACI ) to treat symptomatic cartilage defects of the femoral condyle . Its capacity to safely restore good- quality cartilage was demonstrated in a r and omized controlled trial ( RCT ) versus the surgical procedure microfracture ( MFX ) . Objective : This study investigated the cost utility of CC used in ACI compared with MFX to treat symptomatic knee cartilage lesions in Belgium . Methods : A decision tree model comparing CC with MFX over a 40-year horizon was developed in TreeAge Pro ™ . The key timepoints of the model were ( i ) clinical assessment 5 years after initial intervention ( success or no success , with or without re-operation ) ; ( ii ) development of OA at 15 years ( yes/no ) ; ( iii ) need for TKR at 20 years ( yes/no ) ; and ( iv ) need for prosthesis revision at 35 years ( yes/no ) . Clinical data provided by the RCT of CC versus MFX were the clinical success ( response ) rate based on the Knee injury and Osteoarthritis Outcome Score ( KOOS ) at 36 months ( 82.9 % vs 62.0 % ; p = 0.048 ) and the proportion of good structural repair/presence of hyaline cartilage based on International Cartilage Repair Society ( ICRS II ) visual item at 12 months ( 44.9 % vs 23.2 % ; p= 0.023 ) . Utility scores by surgery outcome were derived from the SF-36 question naire responses collected in the RCT . Conservative assumptions related to the incidences of OA , TKR and prosthesis revision relied on a literature search . A patient chart review ( n = 82 ) provided follow-up costs by surgery outcome . National tariffs were applied to direct medical re sources used ( healthcare payer perspective , year 2008 costs ) . Annual discounting was applied to costs ( 3 % ) and effects ( 1.5 % ) as recommended by the Belgian pharmacoeconomic guidelines . Results : The incremental cost per QALY gained for CC compared with MFX was € 16 229 , with a difference in costs of € 20 802 and 1.282 QALYs gained . Sensitivity analyses indicated that the key model drivers were the proportion of patients with hyaline cartilage and the correlation between hyaline cartilage formation and later avoidance of OA . Probabilistic sensitivity analyses showed robustness of the results , with 80 % of the simulations below the usual UK National Institute for Health and Clinical Excellence ( NICE ) threshold of € 22 000 per QALY . Conclusions : Assuming a good correlation between high- quality cartilage repair and avoidance of OA at a later stage , the benefits of the cell therapy CC over MFX in terms of QALYs gained and OA-related costs avoided appear real . Further research is required to explore long-term effects of cartilage repair and reduce uncertainty on quality of life of patients with OA before and after joint replacement BACKGROUND Despite introduction of autologous chondrocyte therapy for repair of hyaline articular cartilage injury in 1994 , microfracture remains a primary st and ard of care . NeoCart , an autologous cartilage tissue implant , was compared with microfracture in a multisite prospect i ve , r and omized trial of a tissue-engineered bioimplant for treating articular cartilage injuries in the knee . METHODS Thirty patients were r and omized at a ratio of two to one ( two were treated with an autologous cartilage tissue implant [ NeoCart ] for each patient treated with microfracture )  at the time of arthroscopic confirmation of an International Cartilage Repair Society ( ICRS ) grade -III lesion(s ) . Microfracture or cartilage biopsy was performed . NeoCart , produced by seeding a type-I collagen matrix scaffold with autogenous chondrocytes and bioreactor treatment , was implanted six weeks following arthroscopic cartilage biopsy . St and ard evaluations were performed with vali date d clinical outcomes measures . RESULTS Three , six , twelve , and twenty-four- 
    Output:
    