Deubiquitinase USP2 stabilizes the MRE11-RAD50-NBS1 complex at DNA double-strand break sites by counteracting the ubiquitination of NBS1.

The MRE11-RAD50-NBS1 (MRN) complex plays essential roles in the cellular response to DNA double-strand breaks (DSBs), which are the most cytotoxic DNA lesions, and is a target of various modifications and controls. Recently, lysine 48-linked ubiquitination of NBS1, resulting in premature disassembly of the MRN complex from DSB sites, was observed in cells lacking RECQL4 helicase activity. However, the role and control of this ubiquitination during the DSB response in cells with intact RECQL4 remain unknown. Here, we showed that USP2 counteracts this ubiquitination and stabilizes the MRN complex during the DSB response. By screening deubiquitinases that increase the stability of the MRN complex in RECQL4-deficient cells, USP2 was identified as a new deubiquitinase that acts at DSB sites to counteract NBS1 ubiquitination. We determined that USP2 is recruited to DSB sites in a manner dependent on ATM, a major checkpoint kinase against DSBs, and stably interacts with NBS1 and RECQL4 in immunoprecipitation experiments. Phosphorylation of two critical residues in the N terminus of USP2 by ATM is required for its recruitment to DSBs and its interaction with RECQL4. While inactivation of USP2 alone does not substantially influence the DSB response, we found that inactivation of USP2 and USP28, another deubiquitinase influencing NBS1 ubiquitination, results in premature disassembly of the MRN complex from DSB sites as well as defects in ATM activation and homologous recombination repair abilities. These results suggest that deubiquitinases counteracting NBS1 ubiquitination are essential for the stable maintenance of the MRN complex and proper cellular response to DSBs.

Functional alignment maximises advantages of robotic arm-assisted total knee arthroplasty with better patient-reported outcomes compared to mechanical alignment.

PURPOSE: Robotic arm-assisted total knee arthroplasty (RTKA) enables adjustment of implant position to achieve the surgeon's preferred alignment. However, the alignment concept that most effectively enhances patient satisfaction remains unclear. This study compares the clinical outcomes of patients who underwent functionally aligned RTKA (FA-RTKA), mechanically aligned conventional TKA (MA-CTKA) and mechanically aligned RTKA (MA-RTKA). METHODS: A prospectively collected database was retrospectively reviewed for patients who underwent primary TKA for knee osteoarthritis. One hundred and forty-seven knees were performed with MA-CTKA, followed by 72 consecutive knees performed with MA-RTKA, and subsequently, 70 consecutive knees performed with FA-RTKA were enrolled. After 1:1 propensity score matching of patient demographics, 70 knees were finally included in each group. The extent of additional soft tissue release during surgery was identified, and the Coronal Plane Alignment of the Knee classification was utilised to categorise the alignment. At the 1-year follow-up, patient-reported outcomes, including the pain Visual Analogue Scale, Knee Society Score, Western Ontario and McMaster Universities Arthritis Index and Forgotten Joint Score-12, were also compared among the groups. RESULTS: The FA-RTKA group showed significantly less additional soft tissue release than the MA-CTKA and MA-RTKA groups (15.7%, 38.6% and 35.7%, respectively; p = 0.006). Statistically significant differences in functional scores were observed in the postoperative 1-year clinical outcomes in favour of the FA-RTKA group, which had a significantly larger percentage of knees that maintained constitutional alignment and joint line obliquity than those of the other groups. CONCLUSIONS: Functionally aligned TKA showed superior 1-year postoperative patient-reported outcomes compared with those of conventional and robotic arm-assisted mechanically aligned TKA. Therefore, the advantage of RTKA is maximised when the implant positioning is based on functional alignment. The application of RTKA with mechanical alignment has been proven ineffective in improving the clinical outcomes of patients. LEVEL OF EVIDENCE: Level III.

Evaluating the Safety and Effectiveness of Quick-Soluble Gelatin Sponge Particles for Genicular Artery Embolization for Chronic Knee Pain Associated with Osteoarthritis.

PURPOSE: To evaluate the effectiveness and safety of genicular artery embolization (GAE) using quick-soluble gelatin sponge particles (QS-GSPs) to alleviate chronic knee pain associated with osteoarthritis. MATERIALS AND METHODS: This retrospective study included 71 patients (97 procedures, including 26 patients for both knees) who underwent GAE to treat osteoarthritic knee pain between August 2019 and January 2022. QS-GSPs were used for all the procedures. Technical success was defined as the embolization of at least 1 feeding artery. Clinical outcomes were evaluated using a 10-point visual analog scale (VAS). Clinical success was defined as a decrease in the VAS score of >50%. RESULTS: The technical success rate was 100% (97 of 97). The mean VAS scores at baseline, immediately after TAE, and at 1 day, 1 week, 1 month, 3 months, and 6 months after TAE were 6.3, 4.3, 5.0, 3.0, 2.9, 2.9, and 2.8, respectively. The clinical success rate was 72% (70 of 97 patients) at 6 months. No major adverse events were reported, and temporary skin color change (50.5%, 49 of 97) and hematoma at the puncture site (10.3%, 10 of 97) were observed. CONCLUSIONS: GAE using QS-GSPs had a high technical success rate and was considered safe. Clinical outcomes using QS-GSPs were comparable with those of existing materials.

Preoperative patellar bone marrow lesions with full thickness cartilage defects correlate with residual anterior knee pain in total knee arthroplasty without patellar resurfacing.

PURPOSE: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. METHODS: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. RESULTS: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. CONCLUSIONS: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. LEVEL OF EVIDENCE: III.

Beneficial Effect of Curved Dilator System for Femoral Tunnel Creation in Preventing Femoral Tunnel Widening after Anterior Cruciate Ligament Reconstruction.

Backgrounds and objectives: A prevalent concern in anterior cruciate ligament (ACL) reconstruction is postoperative tunnel widening. We hypothesized that employing a curved dilator system (CDS) for femoral tunnel creation can reduce this widening after ACL reconstruction compared to the use of a conventional rigid reamer. Materials and Methods: A retrospective study was conducted involving 56 patients who underwent primary ACL reconstruction between January 2012 and July 2013. The patients were categorized into two groups: the reamer group (n = 28) and CDS group (n = 28). All participants were followed up for a minimum of 2 years. Clinical assessment included the Lachman test and pivot-shift test, and the Lysholm score and subjective International Knee Documentation Committee scores. Radiographic evaluation covered the tunnel widening rate, represented as the ratio of the tunnel diameter 2 years after surgery to the tunnel diameter immediately after surgery, and the ratio (A/B) of femoral tunnel (A) to tibial tunnel (B) diameters at respective time points. Results: No significant disparities were found between the two groups in terms of clinical outcomes. However, the reamer group exhibited a greater femoral tunnel widening rate compared to the CDS group (reamer group vs. CDS group: 142.7 ± 22.0% vs. 128.0 ± 19.0% on the anteroposterior (AP) radiograph and 140.8 ± 14.2% vs. 122.9 ± 13.4% on the lateral radiograph; all p < 0.05). Two years post-operation, the A/B ratio rose in the reamer group (0.96 ± 0.05→1.00 ± 0.05 on the AP radiograph and 0.94 ± 0.03→1.00 ± 0.0.04 on the lateral radiograph; all p < 0.05), while it decreased in the CDS group (0.99 ± 0.02→0.96 ± 0.05 on the AP radiograph and 0.97 ± 0.03→0.93 ± 0.06 on the lateral radiograph; all p < 0.05). Conclusion: The use of CDS for femoral tunnel creation in primary ACL reconstruction provides a potential advantage by limiting tunnel widening compared to the conventional rigid-reamer approach.

The Association of Intravenous Iron Administered the Day before Total Knee Arthroplasty with Postoperative Anemia and Functional Recovery.

Background and Objectives: Total knee arthroplasty (TKA) involves blood loss, increasing the risk of postoperative anemia and delayed functional recovery. Intravenous (IV) iron supplementation limits postoperative anemia; however, the effectiveness of IV iron, administered one day before TKA, on postoperative anemia and functional recovery has scarcely been studied. Materials and Methods: We conducted a retrospective cohort study with propensity score matching using two consecutive groups of patients who underwent TKA using tranexamic acid: the iron group received 500 mg ferric derisomaltose intravenously one day before surgery (n = 46); the non-iron group did not (n = 46). Hemoglobin (Hb) level was determined at postoperative days (PODs) 2, 4, 6, 14, and 30. Ferritin, transferrin saturation (TSAT), and functional iron deficiency anemia (IDA) rate were measured at PODs 2, 4, 6, and 14. Length of hospital stay and transfusion rate were also evaluated. Results: The iron group had higher Hb levels at PODs 6, 14, and 30 and higher ferritin and TSAT at PODs 2, 4, 6, and 14. The functional IDA rate was significantly higher in the non-iron group at PODs 2, 4, 6, and 14. Length of hospital stay was significantly shorter in the iron group; however, the rate of transfusion did not differ between the two groups. Conclusions: IV iron administered one day before TKA was associated with postoperative anemia recovery and length of hospital stay; however, it did not lower the postoperative transfusion rate.

Additional Anterolateral Ligament Reconstruction Helps Patients Improve Dynamic Postural Stability in Revision Anterior Cruciate Ligament Reconstruction.

Background and Objectives: The goal in treating anterior cruciate ligament (ACL) injury especially in revision cases is return to sports activity by regaining dynamic postural stability. Among various methods to achieve this goal, additional anterolateral ligament reconstruction (ALLR) is gaining attention. The purpose of this study was to evaluate the effects of additional ALLR in revision ACL reconstruction (RACLR). Materials and Methods: Patients who underwent RACLR between July 2015 and June 2018 were enrolled. The exclusion criteria were less than 1-year follow-up, age older than 45 years, concomitant multiple ligament injuries, contralateral knee injury, subtotal or total meniscectomized state, and articular cartilage lesions worse than Outerbridge grade 3. Thirty-nine patients (20 patients; RACLR only (Group A), 19 patients; RACLR with additional ALLR (Group B)) were included. Clinical scores (Lysholm score, subjective International Knee Documentation Committee (IKDC) score, Tegner activity scale), isokinetic strength test, single-leg-hop for distance test (SLHDT), Y-balance test (YBT) were checked preoperatively and 1-year postoperatively. Results: Limb symmetry index values in YBT showed significantly better result in Group B 1-year postoperatively (Group A: 97.2 ± 4.0, Group B: 100.3 ± 2.9, p = 0.010), although there were no differences preoperatively between groups (Group A: 90.4 ± 6.7, Group B: 89.3 ± 5.5, p = 0.594). Regarding clinical scores, isokinetic strength tests, and SLHDT, there were no differences between groups preoperatively nor 1-year postoperatively. Conclusions: Additional ALLR in RACLR helped patients gain better dynamic postural stability at 1-year postoperative follow-up.

Stable maintenance of the Mre11-Rad50-Nbs1 complex is sufficient to restore the DNA double-strand break response in cells lacking RecQL4 helicase activity.

The proper cellular response to DNA double-strand breaks (DSBs) is critical for maintaining the integrity of the genome. RecQL4, a DNA helicase of which mutations are associated with Rothmund-Thomson syndrome (RTS), is required for the DNA DSB response. However, the mechanism by which RecQL4 performs these essential roles in the DSB response remains unknown. Here, we show that RecQL4 and its helicase activity are required for maintaining the stability of the Mre11-Rad50-Nbs1 (MRN) complex on DSB sites during a DSB response. We found using immunocytochemistry and live-cell imaging that the MRN complex is prematurely disassembled from DSB sites in a manner dependent upon Skp2-mediated ubiquitination of Nbs1 in RecQL4-defective cells. This early disassembly of the MRN complex could be prevented by altering the ubiquitination site of Nbs1 or by expressing a deubiquitinase, Usp28, which sufficiently restored homologous recombination repair and ATM, a major checkpoint kinase against DNA DSBs, activation abilities in RTS, and RecQL4-depleted cells. These results suggest that the essential role of RecQL4 in the DSB response is to maintain the stability of the MRN complex on DSB sites and that defects in the DSB response in cells of patients with RTS can be recovered by controlling the stability of the MRN complex.

Patients with advanced lateral osteoarthritis can return to sports and work after distraction arthroplasty plus lateral meniscal allograft transplantation combined with cartilage repair.

PURPOSE: This study aimed to report return to sports (RTS) and return to work (RTW) outcomes after distraction arthroplasty (DA) plus lateral meniscal allograft transplantation (MAT) combined with cartilage repair in active patients with advanced osteoarthritis. It was hypothesised that DA combined with lateral MAT would improve clinical and radiological outcomes and enable RTS and RTW for most patients. METHODS: In total, 21 patients with advanced osteoarthritis (moderate to severe joint space narrowing at lateral edge on Rosenberg view and large cartilage defect of lateral femoral condyle) who underwent concomitant DA and MAT were retrospectively reviewed. Clinical outcomes were assessed using subjective knee scores [Lysholm score, International Knee Documentation Committee (IKDC) subjective knee score, and Tegner activity scale (TAS)] and functional tests (isokinetic extensor muscle strength test, single-leg vertical jump test, and single-leg hop for distance test). The rates of RTS, RTW, and satisfaction were evaluated. Radiological outcomes were assessed using magnetic resonance imaging (MRI) and X-ray (Rosenberg view). RESULTS: The mean age at surgery and mean follow-up duration were 37.2 ± 5.9 years and 37.1 ± 5.4 months, respectively. All improvements in subjective scores were statistically significant (p < 0.001). The Lysholm score improved from 58.3 ± 8.1 to 84.3 ± 8.2, the IKDC subjective score from 53.9 ± 10.4 to 78.0 ± 7.7, and the TAS from 4.0 ± 0.5 to 5.1 ± 0.8. The limb symmetry index (LSI) (%) of the extensor peak torque at an angular velocity of 60°/s improved from 67.3 ± 19.2 to 88.4 ± 20.3% (p = 0.001). The LSI of the single-leg vertical jump test and single-leg hop for distance test improved from 62.8 ± 21.3 to 87.7 ± 19.5% and from 63.9 ± 20.8 to 85.5 ± 18.1%, respectively (all, p < 0.001). All patients were able to return to any sports activity and work. However, 67% and 90.5% returned to their defined or desired level of sports activity and occupation intensity, respectively. Further, 76.2% were very satisfied or somewhat satisfied with the outcome at the last follow-up. The JSW increased by 0.8 ± 0.4 to 2.3 ± 0.6 mm (p = 0.005). In more than 90% of patients, > 50% of cartilage lesion was covered. The mean graft extrusion was 2.6 ± 1.0 mm. CONCLUSION: All patients who underwent distraction arthroplasty plus lateral MAT combined with cartilage repair returned to any sports and work at the last follow-up. Significant improvements in clinical outcomes and the radiographic joint space width were observed. However, the activity ability was somewhat reduced compared with the best preoperative level. This one-stage joint salvage treatment is a promising option for young and active patients with advanced OA who wish to return to high levels of sports activity and occupation intensity (≥ Tegner activity scale 4). LEVEL OF EVIDENCE: III.

RecQL4 tethering on the pre-replicative complex induces unscheduled origin activation and replication stress in human cells.

Sequential activation of DNA replication origins is precisely programmed and critical to maintaining genome stability. RecQL4, a member of the conserved RecQ family of helicases, plays an essential role in the initiation of DNA replication in mammalian cells. Here, we showed that RecQL4 protein tethered on the pre-replicative complex (pre-RC) induces early activation of late replicating origins during S phase. Tethering of RecQL4 or its N terminus on pre-RCs via fusion with Orc4 protein resulted in the recruitment of essential initiation factors, such as Mcm10, And-1, Cdc45, and GINS, increasing nascent DNA synthesis in late replicating origins during early S phase. In this origin activation process, tethered RecQL4 was able to recruit Cdc45 even in the absence of cyclin-dependent kinase (CDK) activity, whereas CDK phosphorylation of RecQL4 N terminus was required for interaction with and origin recruitment of And-1 and GINS. In addition, forced activation of replication origins by RecQL4 tethering resulted in increased replication stress and the accumulation of ssDNAs, which can be recovered by transcription inhibition. Collectively, these results suggest that recruitment of RecQL4 to replication origins is an important step for temporal activation of replication origins during S phase. Further, perturbation of replication timing control by unscheduled origin activation significantly induces replication stress, which is mostly caused by transcription-replication conflicts.

ATM activation is impaired in human cells defective in RecQL4 helicase activity.

RecQL4 has been shown to be involved in DNA replication and repair, but its role in DNA damage checkpoint pathway has not been reported. Here, we show that RecQL4 plays an important role in the activation of ataxia telangiectasia mutated (ATM)-dependent checkpoint pathway in human cells. Cells depleted with RecQL4 or Rothmund-Thomson syndrome cells showed significant impairment in the activation of ATM and the downstream effector proteins such as checkpoint kinase 2 and p53 after DNA damage. This defect was recovered with the expression of wild type RecQL4 but not any mutant RecQL4 proteins with defective helicase activities. While RecQL4 failed to show any direct interaction with ATM, it stably interacted with the Mre11-Rad50-Nbs1 complex that is essential for the activation of ATM and was localized on the DNA damage foci. Thus, our results suggest that the helicase activity of RecQL4 plays an important role in the activation of ATM-dependent checkpoint pathway against DNA double strand breaks in human cells.

What is the Natural History of the Triangular Fibrocartilage Complex Tear Without Distal Radioulnar Joint Instability?

BACKGROUND: The triangular fibrocartilage complex (TFCC) tear is a common cause of ulnar-side wrist pain; however, its natural course is not well understood. QUESTIONS/PURPOSES: We sought (1) to determine the natural course of TFCC tears without distal radioulnar joint (DRUJ) instability, and (2) to identify the factors associated with poor prognosis after nonsurgical treatment of TFCC tears. METHODS: Over a 3-year period, we treated 117 patients with TFCC tears who did not have DRUJ instability. The diagnosis was made on the basis of ulnar-sided wrist pain, a positive ulnocarpal stress test or ulnar grinding test, and identification of a tear on MRI or CT arthrography. Of those, 25 were excluded during the initial evaluation period because they met the previously defined indications of surgery on the basis of clinical history. Another 19 patients (20%) were lost to followup before 6 months, and one patient was excluded because of prior wrist surgery, leaving 72 wrists in 72 patients for analysis in this retrospective study, which drew data from a review of electronic medical records of one institution. The group consisted of 42 men and 30 women, with a mean age of 40 years (range, 18-70 years). The study group was followed for a mean of 16 months (range, 6 to 36 months). We evaluated the pain VAS and patient-rated wrist evaluation (PRWE) at the initial visit, at 4, 8, and 12 weeks, and at more than 6 months after the initial visit. A PRWE score ≤ 20 points indicated complete recovery, and a PRWE score more than 20 points was considered an incomplete recovery. We used Kaplan-Meier survival analysis and Cox regression modelling to estimate the time to complete recovery and to identify factors associated with incomplete recovery among the seven possible factors of older age (≥ 45 years), male, obesity (body mass index ≥ 30 kg/m), dominant-hand involvement, chronic symptoms (≥ 6 months), traumatic tear, and ulnar-plus variance. RESULTS: The Kaplan-Meier survival analysis showed that estimated cumulative incidence of complete recovery was 30% (95% confidence interval [CI], 20-40) at 6 months and 50% (95% CI, 39-61) at 1 year. We could not find any risk factors among the seven candidate factors, including older age (hazard ratio [HR], 0.608; 95% CI, 0.34-1.087; p = 0.093), male (HR, 1.152; 95% CI, 0.667-1.991; p = 0.612), obesity (HR, 1.433; 95% CI, 0.603-3.402; p = 0.415), dominant hand involvement (HR, 1.808; 95% CI, 0.927-3.527; p = 0.082), chronic symptoms (HR, 0.763; 95% CI, 0.443-1.922; p = 0.133), traumatic tear (HR, 0.756; 95% CI, 0.432-1.32; p = 0.325), and ulnar plus variance (HR, 0.804; 95% CI, 0.461-1.404; p = 0.443). CONCLUSIONS: This study demonstrates that nonsurgical treatment is moderately successful for treating patients with TFCC tears without DRUJ instability. We recommend a minimum of 6 months nonsurgical treatment as the first-line treatment for this injury. Future studies are necessary to clarify predictors of persistent pain with nonsurgical treatment to avoid an unnecessary surgical delay. LEVEL OF EVIDENCE: Level III, prognostic study.

Osteoporosis increases the risk of benign paroxysmal positional vertigo: a nested case-control study using a national sample cohort.

INTRODUCTION: The previous studies suggested an association between osteoporosis and sudden sensory neural hearing loss (SSNHL). The aim of the present study was to evaluate the association between osteoporosis and benign paroxysmal positional vertigo (BPPV). MATERIALS AND METHODS: Data from the Korean National Health Insurance Service-National Sample Cohort of participants who were ≥ 50 years old were collected from 2002 to 2013. A total of 13,484 BPPV participants were matched with respect to age group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia to 53,936 controls. In both the BPPV and control groups, the previous histories of osteoporosis were evaluated. Crude (simple) and adjusted odds ratios (ORs) of osteoporosis for BPPV were analyzed using unconditional logistic regression analyses. Subgroup analyses were conducted according to age, sex, and BPPV frequency. RESULTS: A total of 18.64% (2514/13,464) of the BPPV group and 12.21% (6589/53,936) of the control group had a history of osteoporosis (P < 0.001). The adjusted OR of osteoporosis for BPPV was 1.29 (95% CI = 1.23-1.35, P < 0.001). In the subgroup analysis according to age and sex, the ≥ 70-year-old men did not demonstrate a high adjusted OR of osteoporosis for BPPV. All other age and sex subgroups demonstrated high adjusted ORs of osteoporosis for BPPV. CONCLUSIONS: Osteoporosis increased the risk of BPPV in the population aged ≥ 50 years. The OR of osteoporosis was higher in the frequent BPPV group than in the less frequent BPPV group.

Does use of the 70° arthroscope improve the outcomes of arthroscopic débridement for chronic recalcitrant tennis elbow?

BACKGROUND: The use of a 70° arthroscope has been reported to provide better visualization of the extensor carpi radialis brevis origin at the lateral epicondyle. We aimed to compare the surgical outcomes of arthroscopic débridement using an additional 70° arthroscope with those using a 30° arthroscope alone in the treatment of chronic recalcitrant tennis elbow. METHODS: A total of 68 consecutive patients who received arthroscopic débridement for chronic recalcitrant tennis elbow were retrospectively reviewed. A 30° scope was used in 41 patients (mean age, 47 years; range, 26-61 years), whereas an additional 70° scope was used in 27 patients (mean age, 50 years; range, 34-61 years). Outcomes were assessed using a visual analog scale for pain and the Quick Disabilities of the Arm, Shoulder and Hand questionnaire at the preoperative visit and at 3 months, 6 months, and 12 or more months after surgery. RESULTS: Both groups showed significant and progressive improvements in visual analog scale pain scores and Quick Disabilities of the Arm, Shoulder and Hand scores at 3 months, 6 months, and final follow-up (P < .05). However, no significant differences were found between the groups at all time points of measurement regarding those outcome measures (P > .05). In addition, the proportions of patients with excellent outcomes and those with clinically meaningful improvements were comparable between the groups (P = .397 and P = .558, respectively). CONCLUSION: The use of an additional 70° arthroscope did not provide a significant improvement in the outcomes of arthroscopic débridement for chronic recalcitrant tennis elbow.

Combined use of topical intraarticular tranexamic acid and rivaroxaban in total knee arthroplasty safely reduces blood loss, transfusion rates, and wound complications without increasing the risk of thrombosis.

BACKGROUND: Blood loss and deep vein thrombosis (DVT) are important complications after total knee arthroplasty (TKA). Topical tranexamic acid (TXA) effectively reduces wound bleeding but may elevate the risk of DVT. In contrast, rivaroxaban potently prevents DVT but has been associated with bleeding complications. The simultaneous use of topical TXA and rivaroxaban in TKA has not been much investigated. METHODS: A retrospective cohort study was conducted with two consecutive groups of patients who underwent TKA. Intraoperatively, one group (RVTX group) received topical, intraarticular TXA, while the other (RV group) did not. Both groups were administered rivaroxaban postoperatively for 14 days and underwent Doppler ultrasound for DVT screening. After propensity score matching, both groups consisted of 52 patients (104 patients in total) and were compared regarding total drain output, nadir haemoglobin (Hb), maximum Hb decrease, calculated total blood loss, transfusion rate, and incidence of DVT and wound complications. RESULTS: Both groups showed no significant differences in the propensity-matched variables of age, sex, body mass index, American Society of Anesthesiologists physical status score, and preoperative Hb. The RVTX group showed a significantly higher nadir Hb (p < 0.001), lower drain output (p < 0.001), Hb decrease (p = 0.015), total blood loss (p < 0.001), and rate of transfusion (p < 0.001) and fewer wound complications (p = 0.027). However, the incidence of DVT (p = 1.000) did not differ significantly between the two groups, and all cases were asymptomatic. CONCLUSIONS: The combined use of intraarticular topical TXA with rivaroxaban in patients undergoing TKA is a safe and effective method to reduce blood loss, the need for transfusion, and wound complications without elevating the risk of DVT.

Rotational alignment of femoral component with different methods in total knee arthroplasty: a randomized, controlled trial.

BACKGROUND: Femoral component rotation (FCR) is one of the most important factors in total knee arthroplasty. In this prospective study, we used three different techniques for FCR and analyzed their accuracy with postoperative axial computed tomography (CT) images. We also evaluated effect of FCR to clinical outcome. METHODS: One hundred sixty-five patients were randomly allocated into three groups. In the measured resection group, FCR was set by externally rotating the axis 3° off the posterior femoral condylar axis. In the tensor group, a gap-tensioning device set at 20 lbf was used. In the block group, spacer blocks of various thicknesses were used. The FCR angle (FCRa) was measured on postoperative axial CT as an angle between the clinical transepicondylar and posterior condylar axes of the femoral component. Outliers were defined as FCRas deviated more than 3° either internally or externally. Postoperative 2 year clinical scores and knee range of motion were checked. RESULTS: The tensor group had significantly better positioning of the femoral component to the neutral position compared with the measured resection group and the block group (mean FCRa: internal rotation 1.79, 0.43 and 2.63°, respectively, p < 0.001). The outliers were also least frequent in the tensor group (35, 16 and 40%, respectively, p = 0.02). There were no significant differences in postoperative 2 year clinical results among groups. CONCLUSIONS: Gap technique with a 20-lbf tensor device was the most accurate and precise method for obtaining adequate FCR. Measured resection with 3° external rotation and gap technique with blocks could lead to internal rotation of the femoral component. Postoperative 2 year clinical results were not significantly different among groups with different techniques for FCR. TRIAL REGISTRATION: The study was registered in the Clinical Research information Service (trial number: KCT0000129 ) in Korea. Registration date is 23rd of June, 2011.

Human Tim-Tipin complex affects the biochemical properties of the replicative DNA helicase and DNA polymerases.

Tim (Timeless) and Tipin (Tim-interacting protein) form a stable heterodimeric complex that influences checkpoint responses and replication fork progression. We report that the Tim-Tipin complex interacts with essential replication fork proteins and affects their biochemical properties. The Tim-Tipin complex, reconstituted and purified using the baculovirus expression system, interacts directly with Mcm complexes and inhibits the single-stranded DNA-dependent ATPase activities of the Mcm2-7 and Mcm4/6/7 complexes, the DNA unwinding activity of the Mcm4/6/7 complex, and the DNA unwinding and ATPase activity of Cdc45-Mcm2-7-GINS complex, the presumed replicative DNA helicase in eukaryotes. Although stable interactions between Tim-Tipin and DNA polymerases (pols) were not observed in immunoprecipitation experiments with purified proteins, Tim was shown to interact with DNA pols α, δ, and ε in cells. Furthermore, the Tim-Tipin complex significantly stimulated the pol activities of DNA pols α, δ, and ε in vitro. The effects of Tim-Tipin on the catalytic activities of the Mcm complexes and DNA pols are mediated by the Tim protein alone, and distinct regions of the Tim protein are responsible for the inhibition of Mcm complex activities and stimulation of DNA pols. These results suggest that the Tim-Tipin complex might play a role in coupling DNA unwinding and DNA synthesis by directly affecting the catalytic activities of replication fork proteins.

Extent of vertical cementing as a predictive factor for radiolucency in revision total knee arthroplasty.

PURPOSE: Limited information is available regarding the effects of cementing extent on implant stability in patients who have undergone revision total knee arthroplasty (TKA). As such, the goals of this study were: (1) to determine the correlation between the extent of vertical cementing and implant loosening; (2) to determine whether the extent of cementing is a potential predictive factor for radiolucency; and (3) to evaluate the minimal amount of cement needed for a stable implant during revision TKA using a hybrid technique. METHODS: One hundred nine stemmed/revision TKAs with a mean follow-up period of 5 years were retrospectively analysed. In each case, a single varus-valgus constrained implant was used and fixed with a hybrid technique. Implant stability was evaluated according to the modified Knee Society radiographic scoring system. The extent of vertical cementing was defined as the longitudinal length from the implant base to the end of the radiopaque line around the stem on radiograph. Its correlation with implant stability was analysed, and the minimal value for a stable implant was evaluated with a receiver operating characteristic (ROC) analysis. RESULTS: The mean extent of vertical cementing was longer in stable implants (femur: p = 0.001, tibia: p = 0.004) and significantly correlated with implant stability (femur: p < 0.001, tibia: p = 0.001). A logistic regression analysis revealed that the risk of loosening was 8.7-16.1 times higher when the extent of cementing was <40 mm, which was located at the stem-implant junction of the modular implant. The minimal extent of vertical cementing was estimated to be 60 mm for a stable femoral implant and 50 mm for a tibial implant. CONCLUSIONS: The hybrid fixation technique with a cementing extent >60 mm for the femur and 50 mm for the tibia was durable at a mean follow-up period of 5 years. Vertical cementing 10-20 mm above the stem-implant junction is recommended when performing revision TKA using this technique. LEVEL OF EVIDENCE: IV.

Anatomy of the anterior cruciate ligament insertion sites: comparison of plain radiography and three-dimensional computed tomographic imaging to anatomic dissection.

PURPOSE: The aim of this study was to provide quantitative data on insertion sites of anterior cruciate ligament (ACL) and to assess the correlation among measurements of anatomic dissection, plain radiographs, and 3D CT images to determine whether radiologic data can accurately reflect real anatomic measurements. METHODS: Fifteen cadaveric knees were assessed using the three measurement modalities. Lengths of the long and short axis, area, and centre position of each bundle insertion sites by quadrant method were examined on both the femur and tibia. Distances from the insertion centre to distal cortical and posterior cortical margins of condyle on femur, and distance between insertion centres on tibia were also inspected. RESULTS: The average ACL insertion position in the three measurement modalities was at 33.9 % in deep-shallow position and at 26.5 % in high-low position for anteromedial (AM) bundle and at 39.2 and 54.8 %, respectively, for posterolateral (PL) bundle in femur. For tibia, it was at 36.9 % in anterior-posterior position and 47.1 % in medial-lateral position for AM bundle and at 43.1 and 53.5 %, respectively, for PL bundle. The slight differences in various measurements among the three modalities were not statistically significant. CONCLUSIONS: The femoral insertion positions were considerably shallow and low, whereas tibial insertion positions were near the average compared to those in previous studies. Plain radiographic and 3D CT measurements showed a reliable correlation with anatomic dissection measurements. The clinical relevance is that plain radiographs rather than 3D CT can be used as a post-operative evaluation tool after ACL reconstruction.

In-situ study of beneficial utilization of coal fly ash in reactive mine tailings.

Oxidation of reactive mine tailings and subsequent generation of acid mine drainage (AMD) have been long recognized as the largest environmental concern for the mining industry. Laboratory studies on utilization of coal fly ash in management of reactive mine tailings have shown reducing water and oxygen infiltration into tailings matrix, thus preventing oxidation of sulphide minerals and acid generation. However, few data from field studies to evaluate the performance of co-placement of mine tailings and fly ash (CMF hereafter) are reported in the open literature. This paper documents the construction and instrumentation of three CMF systems on the Musselwhite mine located in Ontario, Canada and presents results of 3-year real time monitoring. The field data indicates that the CMFs reduced the ingress of water due to cementation generated by hydration of fly ash. It was also found that the electrical conductivity of leachate from CMFs decreased in the early stage of co-placement, compared to the control. With further study, the principle and approach demonstrated in this paper can be adopted as a sustainable technology in the mine tailings management.