Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage.

OBJECTIVE: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. METHODS: OA progression was examined in wild-type and Irf1-/- mice using histologic assessments and microcomputed tomography analysis of whole-joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase-accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ-H2AX foci and senescence-associated beta-galactosidase activity. RESULTS: Our genome-wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon-responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down-regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post-traumatic OA in mice. CONCLUSION: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.

The Relationship between Western Ontario and McMaster Universities Osteoarthritis Index Score and Satisfaction after Total Knee Arthroplasty Changes Over Time.

This study aimed to determine whether there was a relationship between preoperative patient-reported outcome measures (PROMs) and satisfaction after total knee arthroplasty (TKA), and whether there was a relationship between the amount of improvement in PROM or final PROM and satisfaction and whether that relationship differed 1 and 2 years after TKA. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and satisfaction of 267 limbs who underwent TKA were analyzed. Logistic regression analysis was performed to determine whether there was a relationship between preoperative WOMAC or improvement in WOMAC or final WOMAC and satisfaction at 1 and 2 years after TKA. Pearson and Filon's z test was performed to determine whether there was a difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC. There was no significant relationship between preoperative WOMAC and satisfaction. A higher improvement in WOMAC total score and better final WOMAC total scores at 1 and 2 years after TKA were related to greater satisfaction. At 1 year after TKA, there was no significant difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC. However, 2 years after TKA, the final WOMAC function and total score were more related to satisfaction than the amount of improvement in WOMAC function and total score. In the early postoperative period, there was no difference in evaluating satisfaction between the amount of improvement in WOMAC and final WOMAC, whereas over time, the final WOMAC was more related to satisfaction.

Repair of medial meniscus posterior root tear is effective for root healing and cartilage regeneration in opening wedge high tibial osteotomy.

PURPOSE: This study aimed to determine whether the repair of a medial meniscus posterior root tear (MMPRT) is effective for MMPRT healing, cartilage regeneration, and clinical outcomes in opening wedge high tibial osteotomy (OWHTO). METHODS: This retrospective study included 80 patients who underwent OWHTO and subsequent second-look arthroscopy. The patients were divided into OWHTO-with-MMPRT-repair (n = 40) and OWHTO alone (n = 40) groups, and the healing rates (complete/partial/failure) were compared. Each group was further divided into over- and under-corrected subgroups to compare healing rates. The International Cartilage Repair Society (ICRS) grade, cartilage defect size, Koshino stage, ICRS cartilage repair assessment score of the medial femoral condyle (MFC), and International Knee Documentation Committee (IKDC) scores between the OWHTO-with-MMPRT-repair and OWHTO alone groups were compared according to whether microfracture was performed on the MFC. RESULTS: The overall healing rate of the MMPRT was higher in the OWHTO-with-MMPRT-repair group than that in the OWHTO alone group (P < 0.001). In addition, in the subgroup analysis, no difference in the MMPRT healing rate between the over-correction and under-correction groups when MMPRT repair was performed (n.s). In contrast, without MMPRT repair, the healing rate was lower in the under-correction group than that in the over-correction group (P = 0.03). Cartilage regeneration of the OWHTO-with-MMPRT-repair group was superior to that of the OWHTO alone group (P < 0.05). The IKDC subjective scores of the OWHTO-with-MMPRT-repair and OWHTO alone groups were 34.5 and 33.1 before surgery (n.s) and 50 and 47.2 at one year after surgery, respectively (n.s). These differences between the two groups for cartilage regeneration and IKDC subjective scores showed the same pattern regardless of microfractures. CONCLUSIONS: MMPRT repair during OWHTO might improve MMPRT healing, even with under-correction, and cartilage regeneration of MFC, regardless of microfracture. However, OWHTO with MMPRT repair might not improve short-term clinical outcomes compared to OWHTO alone. Further randomized clinical trials are necessary. LEVEL OF EVIDENCE: III, Retrospective cohort study.

Assessment of a novel deep learning-based software developed for automatic feature extraction and grading of radiographic knee osteoarthritis.

BACKGROUND: The Kellgren-Lawrence (KL) grading system is the most widely used method to classify the severity of osteoarthritis (OA) of the knee. However, due to ambiguity of terminology, the KL system showed inferior inter- and intra-observer reliability. For a more reliable evaluation, we recently developed novel deep learning (DL) software known as MediAI-OA to extract each radiographic feature of knee OA and to grade OA severity based on the KL system. METHODS: This research used data from the Osteoarthritis Initiative for training and validation of MediAI-OA. 44,193 radiographs and 810 radiographs were set as the training data and used as validation data, respectively. This AI model was developed to automatically quantify the degree of joint space narrowing (JSN) of medial and lateral tibiofemoral joint, to automatically detect osteophytes in four regions (medial distal femur, lateral distal femur, medial proximal tibia and lateral proximal tibia) of the knee joint, to classify the KL grade, and present the results of these three OA features together. The model was tested by using 400 test datasets, and the results were compared to the ground truth. The accuracy of the JSN quantification and osteophyte detection was evaluated. The KL grade classification performance was evaluated by precision, recall, F1 score, accuracy, and Cohen's kappa coefficient. In addition, we defined KL grade 2 or higher as clinically significant OA, and accuracy of OA diagnosis were obtained. RESULTS: The mean squared error of JSN rate quantification was 0.067 and average osteophyte detection accuracy of the MediAI-OA was 0.84. The accuracy of KL grading was 0.83, and the kappa coefficient between the AI model and ground truth was 0.768, which demonstrated substantial consistency. The OA diagnosis accuracy of this software was 0.92. CONCLUSIONS: The novel DL software known as MediAI-OA demonstrated satisfactory performance comparable to that of experienced orthopedic surgeons and radiologists for analyzing features of knee OA, KL grading and OA diagnosis. Therefore, reliable KL grading can be performed and the burden of the radiologist can be reduced by using MediAI-OA.

A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of a Krill Oil, Astaxanthin, and Oral Hyaluronic Acid Complex on Joint Health in People with Mild Osteoarthritis.

Osteoarthritis is a significant global health problem. Many patients seek more effective alternatives to nonsteroidal anti-inflammatory medicines or commercial supplements to manage joint pain and inflammation. FlexPro MD® (FP-MD) combines krill oil, astaxanthin, and lower molecular weight hyaluronic acid to support joint health. A 12-week, randomized, double-blind, placebo-controlled trial compared the efficacy and safety of FP-MD and placebo once daily in participants (n = 100) with mild osteoarthritis of the knee or hip joint. For the primary endpoint of joint pain score, per-protocol participants (n = 75) in the FP-MD group (n = 37) had a statistically significantly greater mean reduction from baseline in the Korean Visual Analog Scale (K-VAS) at week 12 compared with participants in the placebo group (n = 38) (20.8 ± 16.16 mm vs. 10.6 ± 17.58, p = 0.0105). The Korean Western Ontario and McMaster Universities Osteoarthritis Index (K-WOMAC) total score was also significantly improved in the FP-MD group at week 12 compared with placebo (-13.0 ± 13.62 vs. -5.5 ± 18.08, p = 0.0489), especially an improvement in pain score (-2.5 ± 2.92 vs. -1.3 ± 3.94, p = 0.02635). FP-MD group had greater improvement in joint function scoring by investigator assessment (p = 0.0127) and by group participants (p = 0.0070). A statistically significantly greater number of patients reported adverse events in the placebo group compared with the FP-MD group (16% vs. 4%, p = 0.0455), most commonly gastrointestinal disorders in both of the groups. These findings suggest that FP-MD is well tolerated and can be effectively used to address joint pain in patients diagnosed with mild osteoarthritis, the main symptom of this condition.

A randomized controlled trial for comparing efficacy and safety between intraarticular polynucleotide and hyaluronic acid for knee osteoarthritis treatment.

Although the use of intra-articular polynucleotide (IA PN) injection as a viscosupplement for knee osteoarthritis (OA) treatment has been proposed, its efficacy and safety compared to high molecular weight hyaluronic acid (HMWHA) injection has not yet been established. The present double-blind, multicenter, randomized controlled trial aimed to investigate the efficacy and safety of IA PN injection compared to IA HMWHA injection. A total of 60 patients (15 men, 45 women, 64.5 ± 7.5 years) with knee OA (Kellgren-Lawrence grade 1-4) were randomly allocated to each group. All patients were given three IA injections of PN (n = 30) or HMWHA (n = 30) at intervals of 1 week. The primary endpoint was the change rate in weight-bearing pain (WBP) 16 weeks from the baseline. The secondary endpoint included multiple measurements: the change rate in WBP rate at 8 weeks; the change rate in pain level at rest and during walking at 8 and 16 weeks; the Korean-Western Ontario and McMaster University Osteoarthritis index; the Euro-Quality of Life-5 Dimension; Clinical Global Impression, Patient Global Impression at 8 and16 weeks, and total consumption of rescue medicine. The mean change rate in the WBP at 16 weeks from the baseline was - 54.0 ± 38.1% in the IA PN group and - 42.8 (± 35.8%) in the IA HMWHA group, and there was no significant difference between the two groups (p = 0.296). All secondary endpoints related with pain and functional outcome also showed no significant difference between the two groups. Pain at the injection site and swelling were reported as adverse events, and the incidence was similar between the two groups. IA PN showed comparable efficacy and safety to IA HMWHA at 3 times injection with an interval of 1 week. IA PN can be useful alternative to IA HMWHA for the treatment of knee OA.

Optimal hinge level in opening wedge high tibial osteotomy: Biomechanical analysis using finite element method.

BACKGROUND: While the concept of a safe zone, which can minimize the hinge fracture when performing opening wedge high tibial osteotomy, has been introduced, there is a lack of understanding of the biomechanical environment at the lateral tibial cortex. This study aimed to evaluate the effect of the hinge level on the biomechanical environment at the lateral cortex of the tibia with heterogeneous finite element models. METHODS: Finite element models of biplanar opening wedge high tibial osteotomy based on computed tomography images of a control subject and three patients with medial compartment knee osteoarthritis were created. In each model, three different hinge levels (proximal, middle, and distal) were set. The process of opening the gap during the operation was simulated, and the maximum von Mises stress values at the lateral tibial cortex were calculated for each hinge level and correction angle. FINDINGS: The maximum von Mises stress value at the lateral tibial cortex was the lowest when the hinge was at the middle, while the value was the highest when the hinge was at the distal level. Furthermore, it was demonstrated that a higher correction angle yielded a higher probability of lateral tibial cortex fracture. INTERPRETATION: The findings of this study demonstrate that the hinge at the point where the upper end of the articular cartilage of the proximal tibiofibular joint is located provides the least possibility of lateral tibial cortex fracture, as this is an anatomically independent position from the fibula.

Differences in Resumption of Orthopedic Surgery According to Characteristics of Surgery during COVID-19 Pandemic: National Registry Data.

Background: Healthcare services have been restricted after the coronavirus disease 2019 (COVID-19) outbreak. With the pandemic still ongoing, the patterns of orthopedic surgery might have changed. The purpose of this study was to determine whether the reduced volumes of orthopedic surgery were recovered over time. Among the trauma and elective surgery, which accounted for most orthopedic surgical procedures, we also sought to elucidate whether the changes in the volumes of orthopedic surgery differed according to the type of surgery. Methods: The volumes of orthopedic surgery were analyzed using the Health Insurance Review and Assessment Service of Korea databases. The surgical procedure codes were categorized depending on the characteristics of the procedures. The actual volumes of surgery were compared with the expected volumes to elucidate the effect of COVID-19 on surgical volumes. The expected volumes of surgery were estimated using Poisson regression models. Results: The reducing effect of COVID-19 on the volumes of orthopedic surgery weakened as COVID-19 continued. Although the total volumes of orthopedic surgery decreased by 8.5%-10.1% in the first wave, those recovered to a 2.2%-2.8% decrease from the expected volumes during the second and third waves. Among the trauma and elective surgery, open reduction and internal fixation and cruciate ligament reconstruction decreased as COVID-19 continued, while total knee arthroplasty recovered. However, the volumes of hemiarthroplasty of the hip did not decrease through the year. Conclusions: The number of orthopedic surgeries, which had decreased due to COVID-19, tended to recover over time, although the pandemic was still ongoing. However, the degree of resumption differed according to the characteristics of surgery. The findings of our study will be helpful to estimate the burden of orthopedic surgery in the era of persistent COVID-19.

Comparison of failure rates and functional outcomes between hamstring autografts and hybrid grafts in anterior cruciate ligament reconstruction: A systematic review and meta-analysis.

BACKGROUND: The viability of augmenting small-diameter hamstring autografts with allografts remains unclear. Recent studies have reported different clinical results after allograft augmentation. Hence, we sought to determine whether hamstring autografts and hybrid grafts differed in terms of failure rates and functional outcomes after anterior cruciate ligament (ACL) reconstruction. We also evaluated whether the results of the comparisons differed based on allograft sterilization methods. PATIENTS AND METHODS: This systematic review and meta-analysis were performed by searching the PubMed, Cochrane Library, and EMBASE databases to identify prospective or retrospective studies (evidence levels 1, 2, or 3) that compared the failure rates and functional outcomes of ACL reconstruction using autografts and hybrid grafts. RESULTS: We identified 15 relevant studies, including 1,521 patients, with 798 and 723 treated using autografts and hybrid grafts, respectively. Fourteen studies were retrospective comparative studies, and one was a prospective randomized controlled trial. Of these, three studies used non-irradiated allografts. In the analysis of all participants, no significant differences in failure rates and subjective International Knee Documentation Committee (IKDC) scores were observed between the autograft and hybrid graft groups. Comparing the autograft and hybrid graft groups that used non-irradiated allografts, no differences in the failure rates and subjective IKDC scores were also noted. Meanwhile, in the groups that used irradiated allograft, the autograft group demonstrated higher Lysholm knee scores and reduced anterior laxity than the hybrid graft group. DISCUSSION: Overall, ACL reconstruction using hybrid grafts may not reduce failure rates compared to reconstructions using hamstring autografts, although hybrid grafts with irradiation may decrease functional outcomes. LEVEL OF EVIDENCE: III; systematic review of level II and III studies.

Delayed normalization of C-Reactive protein and erythrocyte sedimentation rate was not associated with inferior clinical outcomes after total knee arthroplasty.

BACKGROUND: The purpose of this study aimed to identify the proportion of patients with delayed normalization of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) after TKA, to determine postoperative thresholds predictive of prolonged elevation. Further, we aimed to determine if the clinical outcomes of patients with prolonged elevation were inferior to those without prolonged elevation. METHODS: The records of 211 unilateral and 320 bilateral TKA were reviewed. Patients were divided into the normal and elevation group based on CRP and ESR levels at 6 weeks and 3 months. The temporal pattern of CRP and ESR change in both groups was compared, and thresholds predictive of elevation at 6 weeks and 3 months were identified. Further, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Tegner activity scale of both groups at 6 months, 1 year, and 2 years after TKA were compared. RESULTS: The proportion of patients with elevated CRP and ESR at 6 weeks and 3 months was CRP: 24.2%, 10%, ESR: 51.6%, 29.9% in unilateral and CRP: 31.5%, 10.6%, ESR: 58.1%, 42.7% in bilateral TKA. The thresholds for elevation at 6 weeks and 3 months were 9.5 mg/dL, 11.4 mg/dL (CRP at 6 weeks) and 81.5 mm/h, 74.5 mm/h (ESR at 3 months). There was no difference in the WOMAC score and Tegner activity scale between both groups. CONCLUSIONS: CRP and ESR are often elevated for a prolonged period even in the absence of infection after TKA. Such cases show distinct temporal patterns, which are predictable, and do not appear to have a significant effect on clinical outcome.

Medial Meniscus Posterior Root Repair Restores Contact Pressure and Contact Area to Its Native State Even After Opening-Wedge High Tibial Osteotomy: A Cadaveric Biomechanical Study.

PURPOSE: To elucidate the effect of medial meniscus posterior root (MMPR) repair during opening-wedge high tibial osteotomy (OWHTO) in terms of contact pressure (CP) and contact area (CA). METHODS: Nine fresh-frozen human cadaveric knee specimens were included. Each specimen was tested under 9 conditions comprising 3 different degrees of correction during OWHTO (neutral, 5° of valgus, and 10° of valgus) and 3 different types of MMPR conditions (intact, torn, and repaired). The prepared specimens were attached to a customized tibiofemoral jig in a fully extended state. The CP and CA generated by a tibiofemoral axial load of 650 N was recorded using the Tekscan sensor's pressure mapping software. Statistical analysis was performed using a repeated measures analysis of variance. RESULTS: The increased CP and decreased CA in torn MMPR was decreased and increased, respectively, to the intact MMPR after repairing, irrespective of whether OWHTO was performed. The mean CP at a correction angle of 5° of valgus was 0.4067 ± 0.0768 MPa for intact MMPR, which increased to 0.7340 ± 0.1593 MPa for the torn MMPR and decreased to 0.3614 ± 0.0639 MPa for the repaired MMPR. In addition, the proportion of decrease in CP and increase in CA after MMPR repair was constant, compared with the torn MMPR, irrespective of the degree of correction during OWHTO. CONCLUSIONS: MMPR repair decreases CP and increases CA, irrespective of whether OWHTO is performed. The biomechanical advantage of repairing torn MMPR is maintained, regardless of the degree of correction during OWHTO. CLINICAL RELEVANCE: Both OWHTO and MMPR repair are known to protect the medial compartment of the knee. However, there are concerns in performing 2 procedures simultaneously. Results of our study showed that concurrent repair of the MMPR during OWHTO is useful for protecting the medial compartment of the knee with respect to tibiofemoral contact biomechanics.

Presence of Night Pain, Neuropathic Pain, or Depressive Disorder Does Not Adversely Affect Outcomes After Total Knee Arthroplasty: A Prospective Cohort Study.

BACKGROUND: A considerable proportion of patients warranting total knee arthroplasty (TKA) have night pain, neuropathic pain, and/or depressive disorder, which may not be resolved by TKA. This prospective, longitudinal cohort study aimed to document the prevalence of night pain, neuropathic pain, and depressive disorder in patients with advanced knee osteoarthritis undergoing TKA and to determine whether the specific coexisting pain and/or disorder at the time of TKA adversely affected postoperative outcomes. METHODS: In this study, 148 patients undergoing TKA were longitudinally evaluated. The presence of night pain, neuropathic pain (determined using Douleur Neuropathique 4 [DN4]) and depressive disorder (determined using the Patient Health Questionnaire-9 [PHQ-9]) was determined before and 6 weeks, 3 months and 1 year after TKA. In addition, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and EuroQol-5 Dimension (EQ-5D) scores were assessed before and 1 year after TKA. Potential associations of night pain, neuropathic pain, and/or depressive disorder with pre- and postoperative WOMAC and EQ-5D scores were examined in subgroup analyses. RESULTS: Preoperatively, 72% (n = 106) of patients reported night pain, and the prevalences of neuropathic pain and depressive disorder were 15% and 17%, respectively. Preoperatively, compared with patients without night pain, those with night pain had significantly poorer preoperative WOMAC scores, but no significant difference was seen between groups 1 year after TKA. Preoperatively, the WOMAC, EQ-5D, and EQ-5D health scores of patients with neuropathic pain were not significantly different from those of patients without neuropathic pain, and there was no difference in clinical outcome scores 1 year after TKA between these groups. Preoperatively, the patients with depressive disorder showed significantly poorer preoperative WOMAC, EQ-5D, and EQ-5D health scores than those without depressive disorder, but no significant differences in scores were observed 1 year after TKA between these groups. CONCLUSION: This study revealed a considerable prevalence of night pain, neuropathic pain, and depressive disorder in patients undergoing TKA and that patients with these specific conditions reported poorer functional and quality of life scores preoperatively. However, such adverse effects disappeared after TKA. Our study findings suggest that TKA can provide satisfactory outcomes for patients with these specific conditions.

Comparative Analysis of T-Score Discordance between a Registry-Based Korean Population and Atypical Femoral Fracture Patients of a Single Institution.

Background: The purpose of this study was to analyze the epidemiology of T-score discordance between the spine and femur in the South Korean population and compare the prevalence of T-score discordance between the Korean osteoporosis population and atypical femoral fracture (AFF) patients. Methods: A total of 12,422 subjects from the Korea National Health and Nutrition Examination Survey were reviewed retrospectively. T-score discordance was defined as a difference of ≥ 1 standard deviation between the lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD). The prevalence of T-score discordance (low LS [LS BMD < FN BMD], low FN [LS BMD > FN BMD], and total [low LS + low FN]) was investigated in the osteoporosis and non-osteoporosis groups and stratified by sex and age. T-score discordance of 63 patients with AFFs diagnosed at a single institution was compared with that of the Korean osteoporosis population using propensity score matching. Results: T-score discordance was prevalent in the Korean osteoporosis population (44.8%), and low LS discordance (37.5%) was more frequently seen than low FN discordance (7.2%) (p < 0.001). The prevalence of total and low LS discordance was significantly higher in AFF patients than in the Korean osteoporosis population (total discordance: 69.8% and 42.5%, respectively; low LS discordance: 63.5% and 31.7%, respectively; p < 0.001). Conclusions: T-score discordance was highly prevalent in the Korean osteoporosis population, and low LS discordance was more common than low FN discordance. Nevertheless, the prevalence of low LS discordance was significantly higher in AFF patients than in the Korean osteoporosis population.

Worse outcome of debridement, antibiotics, and implant retention in acute hematogenous infections than in postsurgical infections after total knee arthroplasty: a multicenter study.

BACKGROUND: We sought to determine (1) the success rate of debridement, antibiotics, and implant retention (DAIR) for acute periprosthetic joint infection (PJI) of the knee in patients with acute postsurgical infection and in those with acute hematogenous infection via a multicenter study, (2) the factors related to the failure of DAIR for overall acute PJI and acute hematogenous PJI via subgroup analysis, and (3) whether the PJI recurrence patterns differed between the two groups over time after DAIR. METHODS: This retrospective multicenter study included 101 acute knee PJI. Acute postsurgical PJI was defined as PJI diagnosed < 3 months following initial knee arthroplasty surgery. DAIR was performed for 34 cases of acute postsurgical PJIs (postsurgical group) and 67 cases of acute hematogenous PJIs (hematogenous group). The success rates between groups were compared, and factors related to DAIR failure were analyzed. RESULTS: The overall success rate of DAIR was 77%. The success rate tended to be higher in the postsurgical group than in the hematogenous group (p = 0.060). However, there was no significant factor related to DAIR failure in the subgroup analysis of acute hematogenous PJIs. In the postsurgical group, the recurrence of PJI occurred until 3 months, whereas in the hematogenous group, recurrence occurred for up to 2 years. CONCLUSIONS: The failure rate tended to be higher in the acute hematogenous PJI group than in the acute postsurgical PJI group. Since acute hematogenous infections may recur for a longer period than postsurgical infections, careful follow-up is required after DAIR.

Effect of severity and cause of preoperative anemia on the transfusion rate after total knee arthroplasty.

This study aimed to (1) evaluate the preoperative Hb cut-off value for transfusion after unilateral and bilateral staged (1 week apart) TKAs, respectively, and (2) determine whether cause of preoperative anemia can affect transfusion rate after TKA. A total of 951 patients who underwent TKA (unilateral: 605, bilateral staged: 346) from 2016 to 2019 were reviewed retrospectively. Patient demographics, comorbidities, preoperative Hb level, surgery types, and cause of anemia were evaluated as possible risk factors. The cut-off values for preoperative Hb level to reduce transfusion after TKA were evaluated in each surgery type. Preoperative Hb level, surgery type, and cardiac disease were identified as the risk factors for transfusion after TKA, and preoperative Hb levels of 11.8 (AUC 0.88) and 12.8 (AUC 0.76) were the cut-off values for transfusion after unilateral and staged bilateral TKAs, respectively. Although transfusion rate was higher in anemia with iron deficiency (ID) group than anemia without ID group, preoperative Hb level was also lower in anemia with ID group than anemia without ID group. Single use of preoperative Hb level with different cut-offs depending on the surgery types can be useful indicator for preoperative optimization regardless of cause of anemia.

Enhanced recovery after surgery for major orthopedic surgery: a narrative review.

BACKGROUND: With increasing interest in enhanced recovery after surgery (ERAS), the literature on ERAS in orthopedic surgery is also rapidly accumulating. This review article aims to (1) summarize the components of the ERAS protocol applied to orthopedic surgery, (2) evaluate the outcomes of ERAS in orthopedic surgery, and (3) suggest practical strategies to implement the ERAS protocol successfully. MAIN BODY: Overall, 17 components constituting the highly recommended ERAS protocol in orthopedic surgery were identified. In the preadmission period, preadmission counseling and the optimization of medical conditions were identified. In the preoperative period, avoidance of prolonged fasting, multimodal analgesia, and prevention of postoperative nausea and vomiting were identified. During the intraoperative period, anesthetic protocols, prevention of hypothermia, and fluid management, urinary catheterization, antimicrobial prophylaxis, blood conservation, local infiltration analgesia and local nerve block, and surgical factors were identified. In the postoperative period, early oral nutrition, thromboembolism prophylaxis, early mobilization, and discharge planning were identified. ERAS in orthopedic surgery reduced postoperative complications, hospital stay, and cost, and improved the patient outcomes and satisfaction with accelerated recovery. For successful implementation of the ERAS protocol, various strategies including the standardization of care system, multidisciplinary communication and collaboration, ERAS education, and continuous audit system are necessary. CONCLUSION: The ERAS pathway enhanced patient recovery with a shortened length of stay, reduced postoperative complications, and improved patient outcomes and satisfaction. However, despite the significant progress in ERAS implementation in recent years, it has mainly focused on major surgeries such as arthroplasty. Therefore, further efforts to apply, audit, and optimize ERAS in various orthopedic surgeries are necessary.

Selenophosphate synthetase 1 deficiency exacerbates osteoarthritis by dysregulating redox homeostasis.

Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The resulting state of oxidative stress drives the pathological transition of chondrocytes during OA development. However, the specific molecular pathways involved in disrupting chondrocyte redox homeostasis remain unclear. Here, we show that selenophosphate synthetase 1 (SEPHS1) expression is downregulated in human and mouse OA cartilage. SEPHS1 downregulation impairs the cellular capacity to synthesize a class of selenoproteins with oxidoreductase functions in chondrocytes, thereby elevating the level of reactive oxygen species (ROS) and facilitating chondrocyte senescence. Cartilage-specific Sephs1 knockout in adult mice causes aging-associated OA, and augments post-traumatic OA, which is rescued by supplementation of N-acetylcysteine (NAC). Selenium-deficient feeding and Sephs1 knockout have synergistic effects in exacerbating OA pathogenesis in mice. Therefore, we propose that SEPHS1 is an essential regulator of selenium metabolism and redox homeostasis, and its dysregulation governs the progression of OA.

Effect of Sequential Intravenous and Oral Tranexamic Acid on Hemoglobin Drop After Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Tranexamic acid (TXA) is typically discontinued on the day of total knee arthroplasty (TKA). However, bleeding may persist for several days. We sought to determine whether sequential administration of intravenous (IV) and oral TXA could reduce hemoglobin (Hb) drop more than IV TXA alone. We also wanted to determine whether the use of additional oral TXA increased the rate of complications of deep vein thrombosis (DVT) or symptomatic pulmonary embolism (PE). METHODS: This prospective, randomized controlled trial included 141 patients. We compared the Hb drop, estimated blood loss (EBL), and transfusion rate of patients receiving IV TXA alone (group IV, n = 48) to those of patients who received IV TXA followed by oral TXA for 2 days (group 2D, n = 46) or 5 days (group 5D, n = 47). IV TXA was administered 10 minutes prior to the tourniquet release and 3 hours after the first IV TXA administration. Computed tomography (CT) was performed on postoperative day 6 to identify radiographic evidence of DVT. We also assessed the prevalence of symptomatic DVT and PE. RESULTS: There were no differences in maximal Hb drop, Hb drops measured at each time point, EBL, or transfusion rate among the 3 groups. The mean maximal Hb drop was 3.5 g/dL in group IV, 3.2 g/dL in group 2D, and 3.4 g/dL in group 5D. The mean EBL was 999.9 mL in group IV, 886.4 mL in group 2D, and 972.5 mL in group 5D. One patient in each group required a transfusion. There were no differences in the prevalence of radiographic evidence of DVT or symptomatic DVT. Symptomatic DVT occurred in 3 patients in group IV and 2 patients in group 5D. One patient in group IV developed a symptomatic PE. CONCLUSIONS: Although there was no increase in the complication rate, the sequential administration of oral TXA for up to 5 days after IV TXA did not decrease Hb drop. Therefore, our findings suggest that sequential use of oral and IV TXA is not recommended. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Asymmetric transepicondylar axis between varus and valgus osteoarthritic knees in windswept deformity can be predicted by hip-knee-ankle angle difference.

PURPOSE: Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters. METHODS: A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior-posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip-knee-ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed. RESULTS: In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p < 0.001). All coronal radiologic parameters, including HKA, LDFA, MPTA, JLCA, and VCA, were significantly different between valgus and varus knees. In correlation analysis, the varus-valgus cTEA difference was significantly correlated with LDFA (r = 0.365, p = 0.021), MPTA (r = 0.442, p = 0.004), and HKA differences (r = 0.693, p < 0.001), with the HKA difference showing the strongest correlation with the cTEA difference. CONCLUSION: In bilateral knee osteoarthritis with WSD, valgus knees showed significantly increased cTEA compared to varus knees, and the cTEA difference positively correlated with the HKA difference between valgus and varus knees. To determine the optimal femoral component rotation during TKA in WSD, assessment of cTEA with pre-operative CT scans or careful intra-operative measurement is recommended, especially in patients with large HKA difference. LEVEL OF EVIDENCE: III, Retrospective cohort study.

Effect of distance between the feet on knee joint line orientation after total knee arthroplasty in standing full-limb radiographs.

PURPOSE: Although knee joint line orientation (KJLO) after total knee arthroplasty (TKA) has been emphasized as an important factor that can affect postoperative knee kinematics, the effect of foot position on KJLO has not been fully understood. This study aimed to (1) identify the anatomical and positional factors that determine KJLO after TKA, and (2) determine the effect of foot position on KJLO after TKA. The hypothesis of this study was that the post-TKA KJLO would change depending on the distance between the feet, as well as the coronal implant positions. METHODS: A total of 92 radiographs from 46 patients who underwent TKA were retrospectively reviewed. Two postoperative standing full-limb anteroposterior radiographs taken with the feet in different positions (with both feet in contact with each other or shoulder width apart) from each patient were evaluated. The correlation between KJLO after TKA and possible anatomical and positional factors, including leg length, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), ankle joint line orientation (AJLO), mechanical tibiofemoral angle (mTFA), and distance between the feet, were analyzed, and the KJLO equation was computed using multiple linear regression. KJLO was also compared among different combinations of valgus or varus alignment of the femoral and tibial components. RESULTS: LDFA, MPTA, AJLO, and distance between the feet were identified as determinants of KJLO after TKA, and the distance between the feet was strongly correlated with KJLO. Based on the KJLO equation (KJLO [°] = 107.548 - 0.441 × LDFA [°] - 0.832 × MPTA [°] + 0.093 × AJLO [°] + 0.037 × ITD [mm]), KJLO changes by 3.7° per 100 mm of distance between the feet. The KJLO of patients with valgus femoral and varus tibial components was more parallel to the ground than those with other combinations. CONCLUSION: KJLO after TKA was strongly affected by the distance between the feet when taking full-limb radiography, and the KJLO changed by 3.7° per 100 mm of distance between the feet. To assess the KJLO after TKA reproducibly, standardization of the distance between the feet is necessary. LEVEL OF EVIDENCE: IV.