Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation.Aims
Methods
To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey.Aims
Methods
The purpose of this study was to elucidate kinematic change according to the implant's specific femoral rotation by using orthosensor (Verasense) implant with three degrees external rotation of femoral rotation rebuilt (Genesis-II) and traditional TKA implant without rebuilt of the femoral rotation (Anthem). Twenty-eight patients (34 knees) underwent TKA using Anthem (Smith & Nephew, Memphis, TN, USA) and 16 patients (22 knees) underwent TKA using Genesis-II (Smith & Nephew, Memphis, TN, USA). Patients were followed up for at least 1 year. Mean age of patients was 71.1 years (range, 60 to 80 years) at the time of surgery. After implantation of femur and tibial components, we applied Verasense, the orthosensor system, to evaluate femoral rollback of the new artificial joint. Femoral rollback was analyzed using digitized screenshot function of Verasense.Purpose
Methods
There are limited previous findings detailed biomechanical properties following implantation with mechanical and kinematic alignment method in robotic total knee arthroplasty (TKA) during walking. The purpose of this study was to compare clinical and radiological outcomes between two groups and gait analysis of kinematic, and kinetic parameters during walking to identify difference between two alignment method in robotic total knee arthroplasty. Sixty patients were randomly assigned to undergo robotic-assisted TKA using either the mechanical (30 patients) or the kinematic (30 patients) alignment method. Clinical outcomes including varus and valgus laxities, ROM, HSS, KSS and WOMAC scores and radiological outcomes were evaluated. And ten age and gender matched patients of each group underwent gait analysis (Optic gait analysis system composed with 12 camera system and four force plate integrated) at minimum 5 years post-surgery. We evaluated parameters including knee varus moment and knee varus force, and find out the difference between two groups.Background
Methods
Total knee arthroplasty using navigation system is known to be more effective than conventional methods in achieving more accurate bone resection and neutral alignment. Mobile bearing is also known to reduce wear and automatically correct rotational mal-alignment of the tibia but the long-term follow-up results of more than 10 years are extremely rare. The purpose of this study is to investigate the results of clinical and radiologic long-term follow-up and complications of total knee arthroplasty using navigation and multi-directional mobile bearing. From 2003 to 2006, a total of 111 navigation TKAs using multi-directional mobile bearing design were carried out and reviewed retrospectively. TKAs were performed by two experienced surgeons at one institute. Of the 111 patients, 102 were women and 9 were men. The mean duration of follow-up was 11.4 ± 1.0 years (range, 10.1 to 14.08 years). Clinical outcomes were evaluated in terms of Knee Society Score, Hospital for Special Surgery score, Western Ontario and McMaster University (WOMAC) score, range of motion and complications. Long-term radiological outcomes and survival rates were evaluated at least 10 years. Average preoperative HSS score was 66.5 ± 9.8 and KSS pain and function score were 25.0 ± 11.8 and 44.5 ± 12.3, respectively. Scores improved to 94.1 ± 8.2, 46.6 ± 11.6 and 88.2 ± 14.6 at the last follow up, respectively. Mean preoperative WOMAC scores of 75.8
There are limited previous findings detailed biomechanical properties following implantation with mechanical and kinematic alignment method in robotic total knee arthroplasty (TKA) during walking. The purpose of this study was to compare clinical and radiological outcomes between two groups and gait analysis of kinematic, and kinetic parameters during walking to identify difference between two alignment method in robotic total knee arthroplasty. Sixty patients were randomly assigned to undergo robotic-assisted TKA using either the mechanical (30 patients) or the kinematic (30 patients) alignment method. Clinical outcomes including varus and valgus laxities, ROM, HSS, KSS and WOMAC scores and radiological outcomes were evaluated. And ten age and gender matched patients of each group underwent gait analysis (Optic gait analysis system composed with 12 camera system and four force plate integrated) at minimum 5 years post-surgery. We evaluated parameters including knee varus moment and knee varus force, and find out the difference between two groups.Background
Methods
Among many factors that influence the outcomes of Total Knee Arthroplasties (TKAs), the mechanical alignment has played major roles for the success of TKA, the survival rates of the implants, and patient functionality. Most, but not all, studies have shown that alignment of the mechanical axis in the coronal plane within a range of 3° varus/valgus is associated with improved long-term function and increased survival rates. Robot-assisted TKA has been developed to improve improves the accuracy and precision of component implantation and mechanical axis (MA) alignment. We hypothesised that robot-assisted TKA would lead to a more accurate leg alignment and component implantation, and thus, improve radiological and clinical outcomes. Between January 2003 and December 2004, a total of 98 primary TKA procedures were compared: 49 using a robotic-assisted procedure and 49 using conventional manual techniques. The cohorts were followed for 121.2 and 119.5 months on average, respectively. Radiographic assessments of the patients were performed preoperatively and at final follow-up and made according to the Knee Society Roentgenographic Evaluation System (KSRES) which included measurements of the coronal mechanical axis and sagittal and coronal inclinations of femoral and tibial components. The radiographic measurements were made using a PACS (Picture Archiving and Communication System). Clinical assessments were performed preoperatively, and at a final follow-up date that was a minimum of postoperative nine years. The clinical results included ranges of motion (ROM), Hospital for Special Surgery (HSS) scores, Western Ontario and McMaster University (WOMAC) scores (for pain and function). The radiographic results showed no statistical differences when comparing the means of the two groups. When considering outliers (defined as error ≥ ±3°) for the mechanical axis, femoral coronal and sagittal inclinations, and tibial coronal and sagittal inclinations, the ROBODOC group had zero outliers for all measurements except for one in tibial sagittal inclination. On the other hand, the conventional group had 12 outliers for mechanical axis, 2 for femoral coronal inclination, 3 for femoral sagittal inclination, 3 for tibial coronal inclination, and 4 for tibial sagittal inclination. However, there were no statistically significant differences between groups for ROM, HSS, or WOMAC scores at the final follow-up. The results of this study support previous work and demonstrate that the ROBODOC-assisted implantation of TKA results in better radiographic outcomes and better ligament balance with equivalent safety when compared to conventional TKA at a minimum follow-up of nine years.
Navigation systems that increase alignment accuracies of the lower limbs have been applied widely in total knee arthroplasty and are currently being adopted for minimally invasive UKA (MIS UKA) with good alignment results. There is little debate that when compared with total knee arthroplasty (TKA), UKA is less invasive, causes less morbidity, better reproduces kinematics, and therefore offers quicker recovery, better range of movement and more physiologic function. However, despite improved alignment accuracies, advantages of use of navigation system in UKA in clinical outcomes and survivals are still debatable. To the best of our knowledge, no reports are available on the long-term results after UKA performing using a navigation system. The purpose of this prospective study was to compare the radiological, clinical, and survival outcomes of UKA that performed using the navigation system and using the conventional technique at average 8 years follows up. Between January 2003 and December 2005, Total of 98 UKAs were enrolled for this study, 56 UKAs in the navigation group and 42 UKAs in conventional group were included in this study after a average 8 years follow-up. At the final follow up, the radiological measurements with regard to the mechanical axis, the inclination of the femoral and tibial components, and radiolucent line or loosening were evaluated and compared between two groups. The clinical evaluations were performed using range of motion, Western Ontario and McMaster Arthritis index (WOMAC) scores and Knee Society (KS) score.Background
Methods
Despite the excellent clinical success of total knee arthroplasty (TAK), controversy remains concerning whether or not to resurface the patella. This has led to a number of randomized controlled trials. Randomized controlled trials constitute the most reliable source of evidence for the evaluation of the efficacy of a potential intervention. But most of these studies include all degree of osteoarthritis of the patellofemoral joint. So we did this prospective study to compare clinical and radiological outcomes after TKA with or without patellar resurfacing in patients with grade IV osteoarthritis on patellofemoral joint. 123 cases (93 patients) with Kellgren-Lawrence grade IV osteoarthritis on patellofemoral joint were enrolled for this study. At the operating room, they were randomly assigned to undergo patella resurfacing (62 cases) or patella retention (61 cases). Among them, 114 cases that could be followed for more than 2 years were included in this study (resurfacing group; 59 cases, retention group; 55 cases). When patellar retention was performed, osteophytes of the patella were removed and marginal electrocauterization was carried out. Preoperative and postoperative clinical outcomes were evaluated and compared regarding the Hospital for Special Surgery Patellar (HSSP) score (total 100 point; anterior knee pain, functional limitation, tenderness, crepitus, Q-strength). We also compared Hospital for Special Surgery (HSS) and WOMAC scores, and range of motion (ROM). We also compared radiological outcomes at the final follow up, with regards to mechanical axis of the lower limb, patella tilt and patella congruence angle between two groups.Background
Materials and Methods
The most important factors affecting the outcome of a TKA are restoring the normal mechanical axis and achieving optimum soft tissue balance. In the measured resection technique may have accompanying problems in imbalanced patients. Secondly individual variability of the reference points may affect the alignment of the bony cuts and thereby the alignment of the implant. The gap balance technique blends the soft tissue balance with the bony cuts and tries to overcome this problem. However proponents of the measured resection technique argue that no consideration is given to the coronal and rotational alignment of the femoral component in the gap balance technique. The ligament specific navigation assisted gap balance technique, tries to overcome these fallacies. The lateral ligaments and soft tissues act as a reference against which the medial soft tissues are balanced. Thus the reference becomes individualized and any variability is taken care of. Navigation assistance ensures control of the coronal and rotational alignment of the femoral component. The aim of the present study was two fold: - To describe our methodology of ligament specific navigation assisted gap balance technique and analyze the clinico-radiological outcome of our technique over an eight year follow up. 79 patients (98 knees) with primary osteoarthritis with varus deformity and flexion deformity of were followed up for eight year duration. After obtaining an optimum gap balance and neutral axis in extension, tibial osteotomy perpendicular to the mechanical axis in both the coronal and sagittal planes was done. At this stage joint gaps were distracted in extension and 90â�° flexion. Based on the gap values patients were classified into three groups. Group 1 was the balanced group with flexion extension gap difference ≤2mm, group 2 was the flexion tight group with flexion gap smaller than the extension gap by ≥3mm and group 3 was the extension tight group with the extension gap smaller than the flexion gap by ≥3mm. Thereafter flexion gap balance was achieved only by adjusting the cutting levels of the distal and posterior condyles and adjusting the axial rotation of the femoral component without any further soft tissue release. Intraoperative navigation readings were recorded. All patients were followed clinico-radiologically at 1, 4, and 8 years post operatively.Background
Methods
Stability of total knee arthroplasty (TKA) is dependent on correct and precise rotation of the femoral component. Multiple differing surgical techniques are currently utilized to perform total knee arthroplasty. Accurate implant position have been cited as the most important factors of successful TKA. There are two techniques of achieving soft gap balancing in TKA; a measured resection technique and a balanced gap technique. Debate still exists on the choice of surgical technique to achieve the optimal soft tissue balance with opinions divided between the measured resection technique and the gap balance technique. In the measured resection technique, the bone resection depends on size of the prosthesis and is referenced to fixed anatomical landmarks. This technique however may have accompanying problems in imbalanced patients. Prediction of gap balancing technique, tries to overcome these fallacies. Our aim in this study was twofold: 1) To describe our methodology of ROBOTIC TKA using prediction of gap balancing technique. 2) To analyze the clinico-radiological outcome our technique comparison of meseaured resection ROBOTIC TKA after 1year. Patients that underwent primary TKA using a robotic system were included for this study. Only patients with a diagnosis of primary degenerative osteoarthritis with varus deformity and flexion deformity of were included in this study. Patients with valgus deformity, secondary arthritis, inflammatory arthritis, and severe varus/flexion deformity were excluded. Three hundred ten patients (319 knees) who underwent ROBOTIC TKA using measured resection technique from 2004 – 2009. Two hundred twenty (212 knees) who underwent ROBOTIC TKA using prediction of gap balancing technique from 2010 – 2012. Clinical outcomes including KS and WOMAC scores, and ranges of motion and radiological outcomes including mechanical axis, prosthesis alignments, flexion varus/valgus stabilities were compared after 1year.Background
Methods
One of advantages of single-radius femoral design was to offer better ligament stability based on a maintained isometry of extensor muslce during the whole range of motion. The purpose of this study was to compare intraoperative varus-valgus laxities from 0° to 90° of flexion in patients that received TKA using either a single-radius femoral design or multiradius femoral design. 56 TKAs with a single-radius femoral design (SR group) and 59 TKAs with multiradius femoral design (MR group) were included in this study. We measured and compared varus-valgus laxities at 0°, 30°, 60°, 90° of flexion using the navigation system and manual force between the 2 groups.Background
Methods
This prospective study was undertaken to compare the clinical and radiological results and the in vivo stabilities of anteromedial (AM) and posterolateral (PL) bundle augmentation during anterior cruciate ligament (ACL) reconstruction. Forty-two ACL partial tears that underwent isolated bundle augmentation (22 AM and 20 PL bundles) were evaluated with a minimum follow-up of 1 year. For in vivo intraoperative stability testing, anteroposterior and external/internal rotation stabilities were measured at 0, 30, 60, and 90° of flexion using a navigation system. Ranges of motion, Lachman and pivot shift test results, Tegner activity scores, and Lysholm knee scores of the AM and PL bundle groups were compared. In addition, Telos arthrometer determined stabilities were compared. In-vivo intraoperative stability testing showed that mean preoperative anterior translation at 30° of flexion was greater in the AM group (8.7 vs. 6.5, p = 0.04), whereas mean rotational amount was larger in the PL group (by 2.9 at 0° and 3.6 at 30° of flexion). After ACL reconstruction, no significant differences were found between the two groups in terms of anterior and rotational stabilities at any flexion angle. Furthermore, clinical outcomes in the two groups were not significantly different. Lachman and pivot shift test results and instrumented laxity findings were similar for the two groups at final follow up. In this study, the authors carefully preserved the remnant injured ACL, and achieved excellent anterior stability recoveries and good rotatory stabilities. No significant intergroup difference was found in terms of intraoperative stability or clinical parameters after ACL reconstruction.
The purpose of this study were to evaluate early intra-operative experiences of a custom-fit total knee arthroplasty (TKA) system and to determine the precision of long leg alignment and component placement achieved using this system. Seventeen patients underwent sagittal MRI of an arthritic knee to determine component placement for TKA from October 2010 and March 2011. Cutting guides were machined to control all intra-operative cuts, and cutting guide placements were recorded by navigation system. Radiographic parameters regarding mechanical axis changes, and inclinations of the femoral and tibial components were measured. Outcome was defined as “excellent” when values of each parameters were within ± 2°, as “acceptable” when within ± 3°, and as “outliers” when >± 3° of optimum. The cutting guide placement was within ±2° of the target angle for inclinations of femoral and tibial components. The cutting heights were within 2mm for distal femoral and proximal tibia. Mechanical axis changed from a mean of 8.57° varus to 0.49° valgus, and mean coronal inclinations of femoral and tibial components were 89.52° and 90.12°, respectively, at last follow up visits. There were no outliers and all of them were classified as excellent. Mean sagittal inclinations of the femoral and tibial components were 1.06° and 84.56°, respectively. There were no intra-operative or acute post-operative complications. The custom-fit TKA system system provides an effective, safe means of achieving an accurate mechanical axis and of reducing prosthetic alignment outliers. However, further long term follow-up is needed.
The elevation of the joint line is considered a possible cause of mid-flexion instability in total knee arthroplasty (TKA). The authors evaluated the effects of joint line change on mid-flexion stability in cruciate retaining TKA. Seventy-nine knees treated by cruciate retaining TKA using a modified balanced gap technique were included in this prospective study. After prosthesis insertion, valgus and varus stabilities were measured under valgus and varus stress using a navigation system at 0, 30, 60 and 90° of knee flexion. Changes of joint lines were measured preoperatively and postoperatively and compared. The knees were allocated to a “No change group (≤4mm, 62 patients)” or to an “Elevation group (>4mm, 17 patients)”. Medio-lateral stabilities (defined as the sums of valgus and varus stabilities measured intra-operatively) were compared in the two groups. The mean joint line elevation was 4.6mm in the no change group and 1.7mm in the elevation group. Mean medio-lateral stability at 30° of knee flexion was 4.8±2.3 mm in the no change group and 6.3±2.7 mm in the elevation group, and these values were significantly different (p = 0.02). However, no significant differences in medio-lateral stability were observed at other flexion angles (p>0.05). Knees with a < 5mm joint line elevation provide better mid-flexion stability after TKA. The results of this study suggest that a < 5mm elevation in joint line laxity is acceptable for cruciate retaining TKA.
This study was performed to measure intra-operative varus-valgus laxities from 0° to 90° of flexion during cruciate retaining total knee arthroplasty (TKA) using the modified balanced gap technique. Forty nine patients awaiting unilateral TKA for osteoarthritis were enrolled into this prospective study. Flexion and extension gaps were measured at full extension and at 90° of flexion using a tensioning device before femoral bone cutting. After implantation and closing the medial parapatellar arthrotomy, varus-valgus laxities at 0, 30, 60 and 90° of flexion were also measured using a navigation system. Mean total varus-valgus laxities were significantly less at 0° of flexion (3.8±1.7°) than at the other selected flexion angles. Mean varus laxity was peaked at 3.1±2.2° at 60° of flexion and reached a nadir of 2.0±1.0° at 0° of flexion, which represented a significant difference. On increasing flexion from 0° to 60°, mean valgus laxity increased from 1.8±1.3° to 2.9±1.6°, which was significant, but no significant difference was found for other angles. The use of the balanced gap technique for cruciate retaining TKA using a navigation system, which allows accurate soft tissue balancing via real time gap size feedback, could be helpful for achieving good in vivo laxities throughout range of motion without significant mid flexion laxity.
Recently, axial radiography has received attention for the assessment of distal femur rotational alignment, and satisfactory results have been as compared with the CT method. The purpose of this study was to assess rotational alignment of the femoral component in knee flexion by axial radiography and to compare flexion stabilities achieved by navigational and robotic total knee arthroplasty (TKA). In addition, the authors also evaluated the effects of flexion stability on functional outcomes in these two groups. Sixty-four patients that underwent TKA for knee osteoarthritis with a minimum of follow-up of 1 year constituted the study cohort. Patients in the navigational group (N = 32) underwent TKA using the gap balancing technique and patients in the robotic group (N = 32) underwent TKA using the measured resection technique. To assess flexion stability using axial radiography a novel technique designed by the authors was used. Rotations of femoral components and mediolateral gaps in the neutral position on flexion radiographs was measured and compared. Valgus and varus stabilities under valgus-varus stress loading, and total flexion stabilities (defined as the sum of valgus and varus stability) were also compared, as were clinical outcomes at final follow up visits. A significant difference was found between the navigation and robotic groups for mean external rotation of the femoral component (2.1° and 0.4°, respectively; Both navigational and robotic techniques provide excellent clinical and flexion stability results. Furthermore, axial radiography was found to provide a useful, straightforward means of detecting rotational alignment, flexion gaps, and flexion stability.
The purpose of this study was to compare posterior tibial slope preoperatively and postoperatively in patients undergoing navigational opening-wedge High tibial osteotomy (HTO) and to compare posterior slope changes for 2 and 3-dimentional (D) navigation versions. Between May 2009 and September 2010, 35 patients with unicompartmental osteoarthritis and varus deformity were treated by navigation-assisted open-wedge HTO. Patients were randomly divided into two groups according to the version of the Orthopilot (Aesculap) navigation system used; 2D group (18 patients, 2-D version) and 3D group (17 patients, 3-D version). Radiologic evaluations were conducted using pre- and postoperative leg axes. Posterior slope of proximal tibiae were measured using the proximal tibial anatomic axis method. Postoperatively the mechanical axis was corrected adequately to a mean valgus of 2.81° in 2D group and of 3.15° in 3D group. Mean posterior slopes were well maintained, and measured 7.9° and 10.3° preoperatively and 8.99° and 9.14° postoperatively in 2D and 3D groups, respectively. No significant difference was found between the two navigation versions with respect to posterior tibial slope; mean tibial slope changes were 1.09° and −0.2° in 2D and 3D groups ( Navigation-assisted opening-wedge HTO greatly improves the accuracy of the desired postoperative mechanical femorotibial axis and posterior tibial slope, and the use of 3D navigation results in significantly less change in posterior tibial slope. The authors recommend the use of the 3D navigation because they provide real time intraoperative information about coronal, sagittal, and transverse axis, which are important for the maintenance of a normal posterior tibial slope.
The preoperative prediction of gap balance after robotic total knee arthroplasty (TKA) is difficult. The purpose of this study was to evaluate the effectiveness of a new method of achieving balanced flexion-extension gaps during robotic TKA. Fifty one osteoarthritic patients undergoing cruciate retaining TKA using robotic system were included in this prospective study. Preoperative planning was based on the amount of lateral laxity in extension and flexion using varus stress radiograph. After complete milling by the robot and soft tissue balancing, intra-operative extension and flexion gaps were measured using a tensioning device. Knees were subdivided into three groups based on lateral laxities in 0° and 90° of flexion, as follows; the tight extension group (≥ 2mm smaller in extension than flexion laxity), the tight flexion group (≥ 2mm smaller in flexion than extension laxity), and the balanced group (< 2mm difference between laxities). In addition, intra-operative gap balance results were classified as acceptable (0–3mm larger in flexion than in extension), tight (larger in extension than in flexion) or loose (> 3mm larger in flexion than in extension) based on differences between extension and flexion gaps. During preoperative planning, 34 cases were allocated to the balanced group, 16 to the tight extension group and 1 case was allocated to the tight flexion group. Intra-operative gap balance was acceptable in 46 cases, 4 cases had a tight result, and one case had a loose flexion gap. We concluded that preoperative planning based on the amount of lateral laxity determined using varus stress radiographs may be useful for predicting intraoperative gap balance and help to achieve precise gap balance during robotic TKA.
We hypothesized that navigation can help provide a well-balanced knee, through real-time feedback of alignment accuracies and gap sizes in flexion and extension. The purpose of this study was to evaluate in vivo stabilities of mediolateral laxity in full extension and anteroposterior laxities in 90° of flexion after navigation-assisted total knee arthroplasty, and to determine the nature of the correlations between these and range of motion (ROM). Forty-two total knee arthroplasties performed using a navigation system with a minimum two-year follow-up were included. The following were measured at final follow-ups; mediolateral laxities at extension and anteroposterior laxities at 90 degrees of flexion (using stress radiographs and a Telos arthrometer), modified HSS scores (excluding laxity and range of motion), and range of motion (ROM). At final follow-up the mean modified HSS score was 82% of total points and mean postoperative ROM was 128.1 ± 10.4°. Mean medial laxity was 3.5 ± 1.4°, mean lateral laxity 4.4 ± 2.2°, and mean anteroposterior laxity 7.1 ± 4.1 mm. We found no significant correlation between mediolateral laxity and postoperative ROM. However, a significant correlation was found between postoperative ROM and anteroposterior laxity. In the present study, the use of a navigation system in total knee arthroplasty was found to improve in vivo stability and produce promising short-term clinical results.
