What’s New in Adult Reconstructive Knee Surgery

In this Guest Editorial, we review and summarize the key findings from the most noteworthy and impactful studies relating to adult reconstructive knee surgery across different areas of research over the past year. This review includes studies of various Levels of Evidence, but special attention was paid to higher Levels of Evidence and award-winning publications. Health-Care Policy and Economics As orthopaedic surgeons strive to provide improved patient outcomes, there remains a wide disparity in the equity of health-care access for the most vulnerable patient populations. There is an increased recognition of adverse outcomes based on social determinants of health (SDOH) and of the need for policy and health-care system changes to bridge the gap in patient access and the quality of care that they receive1. The International Classification of Diseases, Tenth Revision (ICD-10) contains Z code categories (Z55-Z65) to document the presence of SDOH. Although these codes currently lack financial incentives for their use, they provide data for tracking and research purposes to identify potential areas for targeted interventions1. In a large database study, Z codes were used to identify matched cohorts of patients with and without SDOH. After the propensity matching of 207,844 patients, the authors observed that patients with disparities in SDOH had higher odds of readmissions and complications within 90 days and higher rates of revision surgery and periprosthetic joint infection (PJI) within 2 years following total knee arthroplasty (TKA) compared with the control group2. One specific socioeconomic metric, the Social Vulnerability Index (SVI), uses 16 variables from the U.S. Census data to identify at-risk communities3,4. Two database studies separately demonstrated that higher SVI was associated with increased length of stay, readmissions, and complications after TKA3, whereas SVI subthemes of household composition and disability were risk factors for 90-day complications following TKA4. These studies encourage a broader adoption of the SDOH and the SVI for screening and preoperative intervention to optimize outcomes in the most vulnerable patient populations. Treatment of Knee Osteoarthritis Biologic interventions to treat knee osteoarthritis and prevent progression remain a trending topic. In a randomized controlled trial (RCT), platelet-rich plasma (PRP) injections alone were compared with exercise and PRP combined with exercise in the treatment of symptomatic grade-2 and 3 knee osteoarthritis. A commercially available kit was used to prepare the PRP injections, which were given 3 times at weekly intervals. Although improvements in patient-reported outcomes were seen in all 3 groups after 24 weeks, the exercise group and the exercise combined with PRP group were superior to the PRP group alone with respect to pain, function, and quality of life. PRP alone had no benefit in treating knee osteoarthritis compared with exercise, allowing the authors to conclude that there is no role of PRP in the treatment of mild to moderate knee osteoarthritis5. Unicompartmental Knee Arthroplasty (UKA) Indications and Utilization The utilization of UKA continues to increase as a treatment for compartment-specific osteoarthritis. A review of the American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination Case List database revealed that the volume of UKAs performed by newly trained surgeons more than doubled between 2011 (18.8 per 10,000 cases) and 2021 (39.5 per 10,000 cases). UKA, compared with periarticular knee osteotomy performed for osteoarthritis, demonstrated significantly lower rates of surgical complications (7.3% compared with 23.7%; p < 0.001), reoperation (1.9% compared with 5.2%; p = 0.002), and infection (1.4% compared with 6.7%; p < 0.001)6. Similarly, a large health-care network database study demonstrated a 590% increase in utilization between 2012 (241 UKAs) and 2022 (1,662 UKAs), with a similar increase in the adoption of robotic UKA (11 in 2012 and 68 in 2022 [518%])7. Lateral UKA There is growing interest in the utilization of lateral UKA for isolated lateral compartment osteoarthritis. In a matched cohort analysis, comparing causes of lateral knee osteoarthritis, all patients had significant functional improvements with respect to the Knee Society Score, Forgotten Joint Score, and visual analog scale (VAS) for pain. Compared with patients with primary lateral knee osteoarthritis, patients who underwent lateral meniscectomy demonstrated less medial compartment osteoarthritis progression and thus significantly greater implant survivorship (97.6% compared with 83.3%) at a mean follow-up of 10 years8. Plancher et al.9 demonstrated that the presence of grade-3 or 4 chondromalacia of the lateral patellar facet did not negatively impact functional scores or survivorship of lateral UKA. Bunyoz et al.10 found a learning curve of approximately 33 cases, based on surgical duration. Oxford Knee Scores (OKS) did not reveal adverse functional outcomes during the learning curve but did reveal 95.4% revision-free survivorship at 7 years10. Similarly, a single-surgeon cohort of 161 lateral UKAs in 153 patients demonstrated revision-free survivorship of 97.4% at 5 years, 95.4% at 10 years, and 91.3% at 15 years11. Registry Data Data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) compared the OKS and survivorship of 3,453 medial UKAs performed with cement and 3,453 cementless medial UKAs in a propensity-matched study. The authors found a greater postoperative mean OKS (39.1 ± 8.7) in the cementless mobile-bearing Oxford UKA cohort compared with the cohort of patients who underwent UKAs performed with cement (38.5 ± 8.6), although the difference was below the minimum clinically important difference (MCID). Additionally, the cementless Oxford UKA had significantly greater 10-year survivorship (93.0%) compared with its cemented counterpart (91.3%). The differences in clinical outcomes were greater, in favor of UKAs performed without cement, when the procedures were performed by high-volume surgeons (≥30 UKAs per year)12. UKA Revision Data from the New Zealand Joint Registry indicated that there is a significantly lower threshold to revise a poorly functioning (OKS, ≤25) UKA compared with a TKA at 6 months (19.6% compared with 5.1%; p < 0.001), 5 years (12.5% compared with 4.3%; p < 0.001), and 10 years (15.0% compared with 6.4%; p = 0.024). The risk of revision for an unknown etiology was approximately 2.5 times higher for UKA compared with TKA13. Acute PJI following UKA presents a unique challenge involving a joint with a prosthetic component as well as native cartilage. A multicenter study explored the effectiveness of debridement, antibiotics, and implant retention (DAIR) in this scenario. The mean time from index UKA to PJI diagnosis was 11.1 months. The eradication rate at 1 year was 80.8% (42 of 52 UKAs), with the failures proceeding to either 1-stage or 2-stage revision to TKA. Although the surgical techniques and irrigation solutions varied widely across institutions, a wide exposure with thorough synovectomy was associated with infection eradication14. Primary TKA Antibiotic Prophylaxis and Infection Prevention Debate persists with regard to the optimal antibiotic prophylaxis for primary TKA. In a multicenter, double-blinded, placebo-controlled superiority trial, the investigators sought to evaluate the efficacy of the addition of intravenous vancomycin compared with placebo in preventing surgical site infection within 90 days postoperatively. Over 4,000 patients without known methicillin-resistant Staphylococcus aureus (MRSA) colonization were included, including 2,233 patients who underwent TKA. Patients received 2 g of cefazolin plus weight-based vancomycin or placebo. Sixty-three (5.7%) of 1,109 patients in the vancomycin group developed a surgical site infection compared with 42 (3.7%) of 1,124 patients in the placebo group (relative risk, 1.52 [95% confidence interval (CI), 1.04 to 2.23]). An additional subgroup analysis on the safety of vancomycin administration yielded a similar rate of adverse events (1.7%) in both groups15. In a systematic review of penicillin allergy in the setting of total joint arthroplasty (TJA), true allergy rates were found to be low (0.7% to 3%). The rate of allergic reaction in patients with a penicillin allergy who received a cephalosporin was 0% to 2%, leading the authors to conclude that perioperative allergy screening and testing can safely increase the usage of first-line antibiotic prophylaxis in TJA16. In a single-blinded RCT of patients undergoing tourniquetless primary TKA, 10 patients received either weight-based intravenous vancomycin 1 hour before the surgical procedure or 500-mg intraosseous vancomycin at the time of incision. Systemic samples prior to incision and at closure showed significantly greater levels of vancomycin in the intravenous group compared with the interosseous group. Intraoperative tissue samples demonstrated similar levels in the intravenous and intraosseous groups, including in samples from the distal femur (61.0 ± 16.0 and 66.2 ± 12.3; p = 0.80), proximal tibia (52.8 ± 13.5 and 57.1 ± 17.0; p = 0.84), and suprapatellar synovial tissue (10.7 ± 5.3 and 9.0 ± 3.3; p = 0.80). The authors highlighted the efficacy of intraosseous vancomycin while avoiding the possible systemic toxicity of vancomycin17. A study from the Catalan Arthroplasty Register of TKAs performed between 2011 and 2020 assessed the association of antibiotic-loaded bone cement (ALBC) and revision rates. Their analysis of 22,781 TKAs (57.6% with plain cement, and 42.4% with ALBC) revealed that the 3-month revision TKA rate for infection was significantly lower in the ALBC group (0.52% compared with 0.78%, p = 0.04)18. Conversely, in a study of 14 national or regional registries, >2 million TKAs were reviewed to compare the risk of 1-year revision for PJI between TKA using ALBC and TKA using plain bone cement. The authors reported a cumulative 1-year revision rate for PJI of <1% in both the ALBC group (range, 0.21% to 0.80%) and the plain cement group (range, 0.23% to 0.70%). There was no significant difference in revision for PJI at 1 year (hazard ratio [HR], 1.16 [95% CI, 0.89 to 1.52]) or for all causes (HR, 1.12 [95% CI, 0.89 to 1.40]) between ALBC and plain bone cement19. Blood Loss Prophylaxis The winners of the American Association of Hip and Knee Surgeons (AAHKS) Clinical Research Award, Kirwan et al.20, investigated the efficacy of extended oral tranexamic acid (TXA) in a double-blinded RCT. Patients who underwent outpatient TKA at a surgery center were randomized to receive 1.95-g oral TXA on the day of the surgical procedure after ambulation and 3 additional doses on postoperative days 1, 2, and 3. The control group took placebo pills in the same manner. The TXA group demonstrated better knee flexion (116.05° compared with 106.5°; p = 0.0308), VAS pain scores (1.35 compared with 2.8; p = 0.011), and Knee Injury and Osteoarthritis Outcome Scores for Joint Replacement) (73.33 compared with 62.47; p = 0.0019) at 6 weeks compared with the placebo group. As the adoption of perioperative TXA administration becomes more universal, an additional benefit of its use is the potential to lower the risk of PJI, with an odds ratio (OR) of 0.63 (95% CI, 0.42 to 0.96; p < 0.001) shown in a recent systematic review and meta-analysis, although it included a small number of studies. The authors hypothesized that TXA prevents PJI by reducing the need for transfusions, postoperative wound drainage, and/or hematoma formation21. Perioperative Care and Pain Management Several new studies assessed the effectiveness of various multimodal anesthesia regimens. In an RCT assessing the efficacy of periarticular injection in the setting of an adductor canal block plus infiltration between the popliteal artery and capsule of the knee (IPACK), a sham saline-solution periarticular injection was found to be noninferior to an active periarticular injection in terms of the pain score and oral morphine equivalents22. Maniar et al.23 demonstrated that an adductor canal block can be safely administered by the surgeon intraoperatively to yield improved pain relief and decreased opioid consumption. Their described technique avoids the need for specialized equipment or an anesthesiologist. In a double-blinded RCT of 106 patients undergoing bilateral TKA, the addition of 20-mg oral duloxetine significantly improved VAS pain scores and patient satisfaction compared with placebo24. Sleep disturbance is a commonly reported symptom after TKA. The winners of the John N. Insall Award, LeBrun et al.25, demonstrated no benefit from exogenous melatonin with respect to subjective sleep quality, opioid usage, or patient-reported outcomes at 6 weeks or 90 days after TKA. The investigators randomized 86 patients each to the melatonin and vitamin C placebo arms of the study in a double-blinded RCT. In a similar double-blinded RCT, Haider et al.26 found a trend toward longer sleep duration in patients taking melatonin for the initial 3 days following TKA, but these attenuating effects on sleep disturbance waned thereafter. Wearable devices that track sleep have gained popularity. In an award-winning study, patient-reported sleep quality returned to baseline by 90 days after TKA. Although sleep metrics, such as time in bed, time asleep, and minutes of REM (rapid eye movement) sleep were nicely captured by the wearable devices, their correlation with patient-reported sleep quality was weak and they may not be a useful objective tracking tool27. Postoperative Complications The winners of the Chitranjan S. Ranawat Award, Abdel et al.28, performed a multicenter RCT to evaluate the efficacy of adjuvant anti-inflammatory medications following manipulation under anesthesia (MUA) for postoperative arthrofibrosis in 124 patients across 15 institutions. Patients were randomized to receive either 8-mg intravenous dexamethasone followed by MUA, physical therapy, and 14 days of oral celecoxib (200 mg) or MUA followed by physical therapy. Range of motion significantly improved in both groups, but, after the MUA, there was no significant difference between the anti-inflammatory group and the control group at 6 weeks (101° compared with 99°; p = 0.35) or at 1 year (108° compared with 108°; p = 0.98). Implant Design Bearing designs in contemporary TKA continue to generate substantial debate. A meta-analysis demonstrated no difference in function and patient-reported outcomes between posterior-stabilized, cruciate-retaining, and ultracongruent liners, although the pooled analysis was limited by the paucity of RCTs and high-quality studies29. In an RCT evaluating a specific single-radius design, patients who had a posterior-stabilized knee implant demonstrated greater flexion compared with patients with a cruciate-retaining knee implant (median, 120.0° compared with 115°; p = 0.017), although functional outcomes were similar at 2 years30. In another RCT involving a different TKA design, knees with posterior-stabilized implants demonstrated greater maximal flexion (129° [95% CI, 127° to 131°]) compared with knees with cruciate-retaining implants (120° [95% CI, 121° to 124°]) and knees with anterior-stabilized implants (122° [95% CI, 120° to 124°]). Similarly, no differences in pain or functional outcomes were seen between the 3 types of liners at the 2-year follow-up31. In a meta-analysis of 11 RCTs, all-polyethylene and metal-backed tibial implants performed similarly with respect to clinical outcomes and survivorship. Five of the studies included radiostereometric analysis (RSA), which showed greater liftoff in the metal-backed group (0.3 mm) compared with the all-polyethylene group (0.19 mm) (p = 0.03); however, this difference was not impactful on clinical outcomes and 5-year survivorship32. Cementless TKAs continue to garner substantial interest. In a paired RCT of bilateral cruciate-retaining TKAs with patellar resurfacing performed under the same anesthetic setting, 1 knee in each of the 40 patients underwent TKA with cement and the other knee underwent TKA without cement. At a minimum 2-year follow-up, functional and pain outcomes were similar in both knees. In 4 of the knees with cementless implants, there was early evidence of superior migration of the metal-backed patellar component on lateral radiographs, none of which required revision33. In another series, metal-backed cementless patellar implants demonstrated 10-year survivorship of 95.9% compared with 98.9% for the cemented implant, with similar rates of patellar revisions (p = 0.151) and patellar aseptic loosening (p = 0.737)34. Concerns remain about metal-backed patellar components, as the most common mode of failure remains polyethylene dissociation from the metal backing35. The commonly held belief of increased early postoperative pain during osseointegration in cementless TKA was debunked in a systematic review and meta-analysis that demonstrated similar short-term (≤6 months) pain and early function compared with TKA performed with cement36. A Canadian Joint Replacement Registry analysis of >202,000 TKAs performed from 2012 to 2021 demonstrated an all-cause revision rate of 4.49% at 2 years for cementless knee implants that was slightly higher than the 3.14% rate for cemented implants when not accounting for confounders. When confounders were taken into consideration, the most common cementless TKA implants demonstrated a lower risk of revision compared with their cemented counterparts, which was significant at 4 years (HR, 0.66 [95% CI, 0.51 to 0.85], p = 0.001). Nonetheless, this database study had multiple limitations that decreased its external validity, given the large number of patient, surgeon, and facility variabilities37. Technology-Assisted TKA The utility of robotic-assisted TKA continues to garner much research interest. In an unblinded RCT comparing manual TKA with a computed tomography (CT)-based robotic-assisted TKA platform, 46 patients who underwent robotic-assisted TKA and 41 patients who underwent manual TKA were assessed at 6 months for pain and functional outcomes. There were no differences in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) functional score (p = 0.425) at 6 months. The robotic-assisted TKA group demonstrated greater improvement in the WOMAC pain score at 2 months (p = 0.037), although this difference was no longer significant at 6 months (p = 0.198). A greater proportion of patients who underwent robotic-assisted TKA, compared with patients who underwent manual TKA, reached the MCID for the WOMAC pain score at both 2 months (36 [78.3%] compared with 24 [58.5%]; p = 0.047) and 6 months (40 [87.0%] compared with 29 [68.3%]; p = 0.036). The proportion of satisfied patients favored robotic-assisted TKA (45 [97.8%] of 46) over manual TKA (36 [87.8%] of 41), although this finding was not significant (p = 0.096)38. A study of the American Joint Replacement Registry (AJRR) comparing 14,216 robotic-assisted TKAs and 128,334 conventional TKAs found no difference in revision risk at 2 years (OR, 1.0 [95% CI, 0.8 to 1.3]; p = 0.92)39. In a review of 300 patients undergoing robotic-assisted TKA in a multicenter study, preoperative CT scanograms demonstrated high correlation with long-leg radiographs for assessing the coronal plane alignment of the knee40. A Markov model incorporating key parameters obtained from the literature (costs of the initial surgical procedure, episode of care, revision, implant failure; probability of complications, 15-year failure rate), computer-assisted TKA was associated with higher quality-adjusted life-years (QALYs) and lower cost compared with conventional TKA. The model further estimates that 100% adoption of computer-assisted TKA would result in nearly $1 billion annually in lifetime cost savings for Medicare and commercial payers41. Revision TKA A variety of topics in revision TKA continue to gain attention internationally. The range of newly published articles is wide and is categorized and summarized next. Implant Design The use of a rotating-hinge component was studied in cases of arthrofibrosis and PJI. The Total Knee Arthrofibrosis (TKAF) Consortium reported on arc-of-motion improvement after revision TKA for arthrofibrosis in 56 patients. The authors reported that there was a significantly greater arc of motion (p < 0.001) for patients treated with a rotating-hinge construct (41.3° ± 19.4°) compared with patients treated with a non-rotating-hinge construct (18.3° ± 15.2°); however, no differences in patient-reported outcomes were seen at the final follow-up. In patients with severe arthrofibrosis (preoperative range of motion, <70°), a mean improvement of 31.1° ± 20.9° in range of motion was seen42. In the infection setting, the use of hinged implants in multistage revisions was reported in 79 patients treated from 2010 to 2018 with minimum 5-year outcomes. Despite the complex surgical history, the patients demonstrated good functional outcomes and 87.3% were free from infection43. PJI The winners of the James A. Rand Young Investigator's Award, Kreinces et al.44, evaluated the utility and necessity of additional tests included in the 2018 Musculoskeletal Infection Society (MSIS) criteria to diagnose PJI. The authors retrospectively reviewed 204 revision TKA cases and 158 revision total hip arthroplasty (THA) cases involving suspected PJI from 2018 to 2020 that had a minimum 2-year follow-up. Most cases (94.6% of TKA cases and 98.7% of THA cases) met the "infected" criteria based on preoperative and intraoperative data without using alpha-defensin or synovial C-reactive protein. When applying preoperative data only, 88.4% of TKA and THA cases met the MSIS criteria for infection, highlighting that an algorithmic approach would be both effective and economical for diagnosing PJI. Several studies over the past year have reviewed the temporal trends in PJI. Data from the New York Statewide Planning and Research Cooperative System found no year-to-year change in the likelihood of revision for PJI among primary TKAs performed from 2006 to 2013. For surgical procedures performed from 2014 to 2016, the likelihood of revision for PJI decreased by year (OR, 0.76 [95% CI, 0.66 to 0.88]; p = 0.0002), which the authors attributed to advances in infection prevention strategies45. Data from the Dutch Arthroplasty Register and the Dutch National Nosocomial Surveillance Network (PREZIES) revealed that early PJI after TKA primarily involved S. aureus (39%), followed by coagulase-negative staphylococci (19%), especially Staphylococcus epidermidis (11%)46. Polymicrobial PJI continues to rise. In a single-center review of PJI comparing 2 time frames (2001 to 2006 and 2018 to 2022), there was a significant increase (p < 0.001) in the involvement of S. epidermidis and Cutibacterium acnes in polymicrobial PJI. Culture data demonstrated that these 2 microorganisms frequently coexisted47. In another study, polymicrobial involvement was found in 41.7% of PJIs following TKA in patients with an overlying sinus tract compared with 29.1% in patients who did not have a sinus tract48. Several studies evaluated the prevalence, outcomes, and implications of unexpected positive cultures during presumed aseptic revisions. In 1 series, the prevalence of 1 or ≥2 unexpected positive cultures for different organisms was 19.5%, whereas the prevalence of 1 uncommon contaminant or ≥2 unexpected positive cultures for the same organism was 4.7%. The presence of unexpected positive cultures was not associated with greater risk of revision at 5 years49. In another series of 691 presumed aseptic revision TKAs, the rates were 7.1% for 1 unexpected positive culture, 1.4% for ≥2 unexpected positive cultures of the same organism, and 0.2% for ≥2 unexpected positive cultures of different organisms. Regression analysis demonstrated that ≥2 unexpected positive cultures of the same microorganism (HR, 11.0; p < 0.001), 1 unexpected positive culture (HR, 4.2; p = 0.018), and the use of hinged constructs (HR, 4.1; p = 0.008) were associated with an increased risk of re-revision for PJI50. The prevalence of unexpected positive cultures during revision of 159 hips and 61 knees for periprosthetic fracture was 6.8% (10 hips and 5 knees). S. epidermidis was the most common causative organism (35%). Re-revision for infection was required in 6 of the 15 patients51. Special Considerations The learning curve of revision TKA was quantified in a single-institution study comparing surgeons grouped on the basis of years in practice ("inexperienced" [little experience; the first 2 years], early experience [4 to 6 years], and senior experience [15 to 17 years]). The duration of the surgical procedure was significantly longer (p < 0.001) for inexperienced surgeons (216.8 minutes) when compared with early experience surgeons (135.1 minutes) and senior experience surgeons (95.0 minutes); however, the rates of reoperation within 1 year were similar: 5.3% for inexperienced surgeons, 3.6% for early experience surgeons, and 5.0% for senior experience surgeons (p = 0.916)52. Evidence-Based Orthopaedics The editorial staff of JBJS reviewed a large number of recently published studies related to the musculoskeletal system that received a higher Level of Evidence grade. In addition to articles cited already in this update, 9 other articles relevant to adult reconstructive knee surgery are appended to this review after the standard bibliography, with a brief commentary about each article to help guide further evidence-based reading in this subspecialty area. Evidence-Based Orthopaedics Di Matteo B, Anzillotti G, Gallese A, Vitale U, Gaggia GMMC, Ronzoni FL, Marcacci M, Kon E. Placenta-derived products demonstrate good safety profile and overall satisfactory outcomes for treating knee osteoarthritis: a systematic review of clinical evidence. Arthroscopy. 2023 Aug;39(8):1892-904. In this systematic review, placenta-derived products demonstrated a good safety profile and good patient-reported outcomes in the treatment of knee osteoarthritis. Sixteen studies were included, of which 5 reported on the use of placenta-derived products for augmentation during surgical procedures. The remaining studies evaluated its use as an injectable therapeutic agent. Although the results are encouraging, the conclusions should be approached with caution, as the study was limited by the inclusion of only 4 RCTs, a lack of a meta-analysis, and the variability of preparation methods. Gupta PK, Maheshwari S, Cherian JJ, Goni V, Sharma AK, Tripathy SK, Talari K, Pandey V, Sancheti PK, Singh S, Bandyopadhyay S, Shetty N, Kamath SU, Prahaldbhai PS, Abraham J, Kannan S, Bhat S, Parshuram S, Shahavi V, Sharma A, Verma NN, Kumar U. Efficacy and safety of stempeucel in osteoarthritis of the knee: a Phase 3 randomized, double-blind, multicenter, placebo-controlled study. Am J Sports Med. 2023 Jul;51(9):2254-66. This was an RCT that assessed the efficacy of allogenic mesenchymal stromal cells compared with placebo in patients with Kellgren-Lawrence grade-2 and 3 osteoarthritis. The placebo consisted of the same 2 mL of the medium used to suspend the bone marrow-derived mesenchymal stromal cells (BMMSC) in the experimental group. Both groups also received 2-mL injections of hyaluronic acid. At 12 months, the WOMAC and VAS pain scores significantly improved in the BMMSC group, whereas those parameters returned to baseline for the placebo group. Magnetic resonance imaging (MRI) revealed gradual worsening of the medial tibiofemoral joint cartilage in the placebo group from baseline to 6 months to 12 months. However, these changes and the cartilage volume did not significantly differ between the 2 groups. The authors present their promising results with novel treatment strategies. Jawanda H, Khan ZA, Warrier AA, Acuña AJ, Allahabadi S, Kaplan DJ, Ritz E, Jackson GR, Mameri ES, Batra A, Dornan G, Westrick J, Verma NN, Chahla J. Platelet-rich plasma, bone marrow aspirate concentrate, and hyaluronic acid injections outperform corticosteroids in pain and function scores at a minimum of 6 months as intra-articular injections for knee osteoarthritis: a systematic review and network meta-analysis. Arthroscopy. 2024 May;40(5):1623-36.e1. In this systematic review and network meta-analysis, the authors evaluated 48 studies including 9,338 knees that underwent intra-articular injections for knee osteoarthritis. Only Level-I and II RCTs were included for review. Hyaluronic acid was injected in 40.9% of the knees, followed by placebo in 26.2%, PRP in 21.5%, cortisone in 8.8%, and bone marrow aspirate concentrate (BMAC) in 2.5%. The pooled results demonstrated that PRP injections yielded greater pain and functional improvements compared with placebo at a minimum of 6 months. Because of the heterogeneity of the included studies, a surface under the cumulative ranking curve (SUCRA) analysis was performed in the network meta-analysis, which demonstrated that PRP had the highest likelihood of improvement compared with BMAC, hyaluronic acid, and cortisone. Although cost was not evaluated in this study, these findings are nevertheless important for clinicians to consider in the approach to the conservative treatment of knee osteoarthritis. Jiao S, Feng Z, Dai T, Huang J, Liu R, Meng Q. High-intensity progressive rehabilitation versus routine rehabilitation after total knee arthroplasty: a randomized controlled trial. J Arthroplasty. 2024 Mar;39(3):665-71.e2. This double-blinded RCT assessed the efficacy of high-intensity progressive training compared with routine therapy following TKA. The investigators and patients were all blinded to the grouping. The high-intensity regimen included preoperative training and was divided into 3 phases (muscle strengthening, active rehabilitation, and weight-bearing training) with a progression process. The routine therapy differed in the lack of progressive training, standardized instructions, and preoperative training, along with a lower frequency of training. A total of 78 patients were equally divided into the 2 training groups. The progressive training group demonstrated greater functional outcomes and patient satisfaction, lower VAS pain scores, and shorter length of stay compared with the routine rehabilitation group. These outcomes demonstrate the efficacy of a high-intensity progressive training program in early recovery, especially as outpatient TKA becomes more popular. Oeding JF, Varady NH, Fearington FW, Pareek A, Strickland SM, Nwachukwu BU, Camp CL, Krych AJ. Platelet-rich plasma versus alternative injections for osteoarthritis of the knee: a systematic review and statistical Fragility Index-based meta-analysis of randomized controlled trials. Am J Sports Med. 2024 Feb 29:3635465231224463. In this systematic review and meta-analysis of RCTs, the authors compared the efficacy of PRP and alternative nonoperative treatments. Ten of the 16 included RCTs represented Level-I evidence, and the remaining 6 RCTs represented Level-II evidence. Outcomes of 1,993 patients were evaluated. The authors assessed the fragility index of all of the studies to determine whether the study outcomes were fragile or robust. Briefly, this involves simultaneously adding and subtracting outcome events in a 2 × 2 contingency table until the significance is reversed. If only 1 event leads to reversal of significance (i.e., fragility index of 1), then the study outcome is deemed fragile and less robust. The meta-analysis demonstrated that PRP had higher rates of symptom improvement, achieving the MCID for pain, and not requiring reintervention compared with alternative injectables, such as hyaluronic acid. The mean number of events required to change the significance of the pooled treatment effect was 8.67 ± 4.50. Based on this fragility index, the conclusions drawn from the meta-analysis are slightly robust and may help the treating physician in determining the optimal nonoperative modality for knee osteoarthritis. Stubnya BG, Kocsis K, Váncsa S, Kovács K, Agócs G, Stubnya MP, Suskó E, Hegyi P, Bejek Z. Subvastus approach supporting fast-track total knee arthroplasty over the medial parapatellar approach: a systematic review and network meta-analysis. J Arthroplasty. 2023 Dec;38(12):2750-8. This systematic review and network meta-analysis compared the early outcomes of TKA according to the surgical approach. A total of 33 RCTs including 2,895 TKAs were included for review. In terms of range of motion, the subvastus and mini-subvastus approaches were generally superior to other approaches (midvastus, mini-midvastus, medial parapatellar) in the first 14 days after TKA. With respect to VAS pain scores, the mini-subvastus was superior on postoperative day 1. In general, the quadriceps-sparing approaches outperformed the medial parapatellar approach for postoperative pain. Functional outcomes also favored the subvastus and mini-subvastus approaches, although these differences all decreased with time. The main limitation of the study was the heterogeneity of time-reporting across all studies (i.e., the sample sizes to compare outcomes were drastically lower at postoperative day 7 compared with postoperative days 42 or 365). Despite this limitation, the results supported the benefits of the quadriceps-sparing approach to TKA. Tao X, Aw AAL, Leeu JJ, Bin Abd Razak HR. Three doses of platelet-rich plasma therapy are more effective than one dose of platelet-rich plasma in the treatment of knee osteoarthritis: a systematic review and meta-analysis. Arthroscopy. 2023 Dec;39(12):2568-76.e2. In this systematic review and meta-analysis of RCTs, the authors sought to compare a single dose with multiple doses of PRP in the treatment of knee osteoarthritis. Seven studies involving 575 patients were included. The knee osteoarthritis ranged from Kellgren-Lawrence grades 1 to 3. At 12 months, triple-dose PRP therapy demonstrated better VAS pain scores compared with single-dose therapy, but this was only based on 3 studies that showed 12-month outcomes. The safety profile was similar between the different PRP doses. The results of this study should be interpreted with caution because of the small number of studies. Additionally, the authors attempted to evaluate WOMAC scores, but omitted the data from the article because of data heterogeneity. Wang Q, Jin Q, Cai L, Zhao C, Feng P, Jia J, Xu W, Qian Q, Ding Z, Xu J, Gu C, Zhang S, Shi H, Ma H, Deng Y, Zhang T, Song Y, Wang Q, Zhang Y, Zhou X, Pei L, Yang Y, Liang J, Jiang T, Li H, Liu H, Wu L, Kang P. Efficacy of diosmin in reducing lower-extremity swelling and pain after total knee arthroplasty: a randomized, controlled multicenter trial. J Bone Joint Surg Am. 2024 Mar 20;106(6):492-500. This RCT evaluated the efficacy of diosmin on postoperative swelling and pain following TKA. Diosmin is a semisynthetic flavonoid derived from hesperidin that is used to treat venous insufficiency. Its mechanism involves its ability to improve venous tone and lymphatic drainage. A total of 330 patients were randomized to either receive or not receive diosmin (0.9 g twice per day for 14 days) after TKA. There was no placebo group. Swelling at the thigh, patella, and calf levels was measured by an assessor blinded to the treatment group. The diosmin group demonstrated significantly less swelling and pain with motion compared with the control group. There were no differences in pain at rest, patient-reported outcomes, range of motion, inflammatory markers, or complication rates. Although early postoperative effectiveness was demonstrated in this study, further studies regarding diosmin's long-term safety are warranted before its widespread use may be recommended. Yoo JD, Huh MH, Lee SH, D'Lima DD, Shin YS. A network meta-analysis of randomized controlled trials assessing intraoperative anesthetic therapies for analgesic efficacy and morphine consumption following total knee arthroplasty. J Arthroplasty. 2024 May;39(5):1361-73. This network meta-analysis of RCTs aimed to compare analgesic effectiveness and morphine consumption after TKA between different modalities. A total of 40 studies were included. Local infiltration anesthesia combined with a saphenous nerve block produced the best analgesic effect after TKA on postoperative days 1 and 2 (SUCRA, 80.0) and the lowest morphine consumption on postoperative days 1 (SUCRA, 80.0) and 3 (SUCRA, 100.0). A femoral nerve block demonstrated the best analgesic effect on postoperative day 3 (SUCRA, 90.0). These results suggest that local infiltration anesthesia combined with a saphenous nerve block should be considered a first-line modality for pain control following TKA.