AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Nonsteroidal Anti-Inflammatory Drugs and Oral Corticosteroids Mitigated the Risk of Arthrofibrosis After Total Knee Arthroplasty.

BACKGROUND: The role of medications to prevent arthrofibrosis following total knee arthroplasty (TKA) remains unclear. We investigated the effect of common oral medications with reported antifibrotic properties on preventing arthrofibrosis and manipulation under anesthesia (MUA) following primary TKA. METHODS: Using our total joint registry, 9,771 patients (12,735 knees) who underwent TKA with cemented, posterior-stabilized, and metal-backed tibial components from 2000 to 2016 were identified. Arthrofibrosis, defined as range of motion (ROM) ≤90° for ≥12 weeks postoperatively or as ROM ≤90° requiring MUA, was diagnosed in 454 knees (4%) and matched 1:2 to controls. Mean age was 62 years (range, 19 to 87) and 57% were women. The majority of operative diagnoses were osteoarthritis. Perioperative use of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin II receptor blockers (ARBs), oral corticosteroids, antihistamines, and nonsteroidal anti-inflammatory drugs (NSAIDs) were manually confirmed. Medication effect in preventing arthrofibrosis and MUA was assessed using adjusted multivariable analyses. Mean follow-up was 8 years (range, 2 to 20). RESULTS: Reduced risk of arthrofibrosis was associated with perioperative NSAID use (odds ratio (OR) 0.67, P = .045). A similar trend was observed with perioperative corticosteroids (OR 0.52, P = .098). Corticosteroids were associated with reduced risk of MUA (OR 0.26, P = .036), and NSAIDs trended towards reducing MUA (OR 0.69, P = .11). CONCLUSION: This investigation determined that perioperative NSAID use was associated with reduced risk of arthrofibrosis and trended towards reduced risk of subsequent MUA. Similarly, oral corticosteroids were associated with reduced risk of MUA and trended towards reduced risk of arthrofibrosis.

Spinal Versus General Anesthesia in Contemporary Revision Total Hip Arthroplasties.

BACKGROUND: Spinal anesthesia is increasingly used in complex patient populations including revision total hip arthroplasties (THAs). This study aimed to investigate the pain control, length of stay (LOS), and complications associated with spinal versus general anesthesia in a large institutional series of revision THAs. METHODS: We retrospectively identified 4,767 revision THAs (4,533 patients) from 2001 to 2016 using our institutional total joint registry. Of these cases, 86% had general and 14% had spinal anesthesia. Demographics between groups were similar with mean age of 66 years, 52% women, and mean body mass index of 29. Complications including all-cause rerevisions and reoperations were studied. Data were analyzed using an inverse probability of treatment weighted model based on propensity score that accounted for patient and surgical factors. The mean follow-up was 7 years. RESULTS: Patients treated with spinal anesthesia required fewer postoperative oral morphine equivalents (P < .001) and had lower numeric pain rating scale scores (P < .001). Spinal anesthesia had a decreased LOS (4.2 versus 4.8 days; P = .007), fewer cases of altered mental status (odds ratio (OR) 3.1, P = .001), fewer blood transfusions (OR 2.3, P < .001), fewer intensive care unit admissions (OR 2.3, P < .001), fewer rerevisions (OR 1.6, P = .04), and fewer reoperations (OR 1.5, P = .02). CONCLUSION: Spinal anesthesia was associated with lower oral morphine equivalent use and reduced LOS in this large cohort of revision THAs. Furthermore, spinal anesthesia was associated with fewer cases of altered mental status, transfusion, intensive care unit admission, rerevision, and reoperation after accounting for numerous patient and operative factors. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Study.

Spinal Versus General Anesthesia in Contemporary Revision Total Knee Arthroplasties.

BACKGROUND: Interest in spinal anesthesia utilization in revision total knee arthroplasties (TKAs) is rising. This study investigated the pain control, length of stay (LOS), and complications associated with spinal versus general anesthesia in a single institution series of revision TKAs. METHODS: We identified 3,711 revision TKAs (3,495 patients) from 2001 to 2016 using our institutional total joint registry. There were 66% who had general anesthesia and 34% who had spinal anesthesia. Mean age, sex, and BMI were similar between groups at 67 years, 53% women, and 32, respectively. Data were analyzed using inverse probability of treatment weighted models based on propensity scores that accounted for patient and operative factors. Mean follow-up was 6 years (range, 2 to 17). RESULTS: Patients treated with spinal anesthesia required fewer postoperative oral morphine equivalents (OMEs) (P < .0001) and had lower numeric pain rating scale scores (P < .001). Spinal anesthesia was associated with shorter LOS (4.0 versus 4.6 days; P < .0001), less cases of altered mental status (AMS; Odds Ratio (OR) 2.0, P = .004), less intensive care unit (ICU) admissions (OR 1.6, P = .02), fewer re-revisions (OR 1.7, P < .001), and less reoperations (OR 1.4, P < .001). There was no difference in the incidence of VTE (P = .82), 30-day readmissions (P = .06), or 90-day readmissions (P = .18) between anesthetic techniques. CONCLUSION: We found that spinal anesthesia for revision TKAs was associated with significantly lower pain scores, reduced OME requirements, and decreased LOS. Furthermore, spinal anesthesia was associated with fewer cases of AMS, ICU admissions, and re-revisions even after accounting for numerous patient and operative factors. LEVEL OF EVIDENCE: Level III, Retrospective Comparative Study.

Patella Fracture Fixation With Novel Wagon Wheel Construct Versus Tension-Band Construct: A Technical Trick.

SUMMARY: Internal fixation of patella fractures remains technically challenging. Cannulated screws with an anterior tension band have been associated with high rates of implant prominence, and fracture comminution can make appropriate application of a tension band impractical. We present the results of a novel technique using a transtendinous/transligamentous mini-fragment plate positioned peripherally around the patella with radially directed screws: termed the wagon-wheel (WW) construct. Compared with a cohort of fractures treated with cannulated screws with an anterior tension band, there was no difference in final range of motion and rate of nonunion. The WW construct had a significantly decreased incidence of symptomatic implants (5% vs. 32%, P = 0.02), rate of reoperation (9% vs. 38%, P = 0.018), dependency on gait aids (10% vs. 38%, P = 0.031), and a faster time to union (HR: 2.2; 95% CI, 1.28-3.95, P = 0.005). In summary, the WW was designed with the goal of obtaining peripheral plate fixation to maximize fragment-specific fixation while minimizing implant prominence. Patients treated with the WW demonstrated reduced rates of implant prominence and reoperation.

Cephalomedullary Nailing of Unstable Geriatric Intertrochanteric Fractures on a Traction Table Combined With Percutaneous Reduction Techniques Is Safe and Results in a Low Rate of Cutout.

OBJECTIVES: To describe a reproducible technique for reduction assessment and percutaneous reduction of unstable intertrochanteric fractures treated with a cephalomedullary nail on a traction table. DESIGN: Retrospective cohort study. SETTING: Level-1 trauma center. PATIENTS: Two-hundred 20 consecutive patients with intertrochanteric fractures. INTERVENTION: Initial closed reduction performed on a traction table. Accessory incisions were used to facilitate a reduction in 77 patients (35%). All fractures were stabilized with a cephalomedullary nail. MAIN OUTCOME MEASUREMENTS: Radiographic outcome including union, cutout, and fracture collapse (FC). Surgical outcomes including infection and hematoma were also reported. RESULTS: Mechanical complications (nonunion, cutout, and varus collapse) occurred in 8.8% of patients at 1 year. Eleven of 13 patients who developed these complications had either suboptimal implant placement (tip-to-apex distance >25 mm) or a varus reduction. There was no difference in the incidence of reoperation, nonunion, lag screw cutout, or posttraumatic arthritis based on the use of an accessory incision for fracture reduction. There was a significant increase in FC in patients who received an accessory incision (6.8 mm vs. 5.4 mm, P = 0.04). One patient (1%) developed a hematoma in the accessory incision cohort, and 1 patient (0.7%) who did not have an accessory incision developed a postoperative infection. CONCLUSIONS: The current study suggests utilization of accessory incisions assist in reduction is safe and is associated with a low rate of complications. The surgeon should prioritize fracture reduction and optimal implant placement and not hesitate to use an accessory incision to assist with fracture reduction. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Knee immobilization reproduces key arthrofibrotic phenotypes in mice.

AIMS: As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). METHODS: Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. RESULTS: Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. CONCLUSION: This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies.Cite this article: Bone Joint Res 2023;12(1):58-71.

Spinal versus general anaesthesia in contemporary primary total knee arthroplasties.

AIMS: Spinal anaesthesia has seen increased use in contemporary primary total knee arthroplasties (TKAs). However, controversy exists about the benefits of spinal in comparison to general anaesthesia in primary TKAs. This study aimed to investigate the pain control, length of stay (LOS), and complications associated with spinal versus general anaesthesia in primary TKAs from a single, high-volume academic centre. METHODS: We retrospectively identified 17,690 primary TKAs (13,297 patients) from 2001 to 2016 using our institutional total joint registry, where 52% had general anaesthesia and 48% had spinal anaesthesia. Baseline characteristics were similar between cohorts with a mean age of 68 years (SD 10), 58% female (n = 7,669), and mean BMI of 32 kg/m2 (SD 7). Pain was evaluated using oral morphine equivalents (OMEs) and numerical pain rating scale (NPRS) data. Complications including 30- and 90-day readmissions were studied. Data were analyzed using an inverse probability of treatment weighted model based on propensity score that included many patient and surgical factors. Mean follow-up was seven years (2 to 18). RESULTS: Patients treated with spinal anaesthesia required fewer postoperative OMEs (p < 0.001) and had lower NPRS scores (p < 0.001). Spinal anaesthesia also had fewer cases of altered mental status (AMS; odds ratio (OR) 1.3; p = 0.044), as well as 30-day (OR 1.4; p < 0.001) and 90-day readmissions (OR 1.5; p < 0.001). General anaesthesia was associated with increased risk of any revision (OR 1.2; p = 0.021) and any reoperation (1.3; p < 0.001). CONCLUSION: In the largest single institutional report to date, we found that spinal anaesthesia was associated with significantly lower OME use, lower risk of AMS, and lower overall 30- and 90-day readmissions following primary TKAs. Additionally, spinal anaesthesia was associated with reduced risk of any revision and any reoperation after accounting for numerous patient and operative factors. When possible and safe, spinal anaesthesia should be considered in primary TKAs.Cite this article: Bone Joint J 2022;104-B(11):1209-1214.

Extended Oral Antibiotic Prophylaxis After Aseptic Revision Total Hip Arthroplasty: Does It Decrease Infection Risk?

BACKGROUND: Extended oral antibiotic prophylaxis (EOA) has been shown to reduce infection after high-risk primary total hip arthroplasties (THAs) and reimplantations. However, data are limited regarding EOA after aseptic revision THAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision THAs. METHODS: We retrospectively identified 1,107 aseptic revision THAs performed between 2014 and 2019. Patients who received EOA >24 hours perioperatively (n = 370) were compared to those who did not (n = 737) using an inverse probability of treatment weighting model. Their mean age was 65 years (range, 19-98 years), mean body mass index was 30 kg/m2 (range, 16-72), and 54% were women. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), and re-revision or reoperation for infection. Mean follow-up was 4 years (range, 2-8 years). RESULTS: The cumulative probability of any infection after aseptic revision THA was 2.3% at 90 days, 2.7% at 1 year, and 3.5% at 5 years. The cumulative probability of PJI was 1.7% at 90 days, 2.1% at 1 year, and 2.8% at 5 years. There was a trend toward an increased risk of any infection (hazards ratio [HR] = 2.6; P = .058), PJI (HR = 2.6; P = .085), and re-revision (HR = 6.5; P = .077) or reoperation (HR = 2.3; P = .095) for infection in patients who did not have EOA at the final clinical follow-up. CONCLUSIONS: EOA after aseptic revision THA was not associated with a statistically significant decreased risk of any infection, PJI, or re-revision or reoperation for infection at all time points. LEVEL OF EVIDENCE: Level III.

Spinal Compared with General Anesthesia in Contemporary Primary Total Hip Arthroplasties.

BACKGROUND: The specific advantages of spinal anesthesia compared with general anesthesia for primary total hip arthroplasty (THA) remains unknown. Therefore, this study aimed to investigate the pain control, length of stay, and postoperative outcomes associated with spinal anesthesia compared with general anesthesia in a large cohort of primary THAs from a single, high-volume academic institution. METHODS: We retrospectively identified 13,730 primary THAs (11,319 patients) from 2001 to 2016 using our total joint registry. Of these cases, 58% had general anesthesia and 42% had spinal anesthesia. The demographic characteristics were similar between groups, with mean age of 64 years, 51% female, and mean body mass index (BMI) of 31 kg/m 2 . Data were analyzed using an inverse probability of treatment weighted model based on a propensity score that accounted for numerous patient and operative factors. The mean follow-up was 6 years. RESULTS: Patients treated with spinal anesthesia had lower Numeric Pain Rating Scale (NPRS) scores (p < 0.001) and required fewer postoperative oral morphine equivalents (OMEs) at all time points evaluated (p < 0.001). Patients treated with spinal anesthesia also had shorter hospital length of stay (p = 0.02), fewer altered mental status events (odds ratio [OR], 0.7; p = 0.02), and fewer intensive care unit (ICU) admissions (OR, 0.7; p = 0.01). There was no difference in the incidence of deep vein thrombosis (p = 0.8), pulmonary embolism (p = 0.4), 30-day readmissions (p = 0.17), 90-day readmissions (p = 0.18), all-cause revisions (p = 0.17), or all-cause reoperations (p = 0.14). CONCLUSIONS: In this large, single-institution study, we found that spinal anesthesia was associated with reduced pain scores and OME use postoperatively. Furthermore, spinal anesthesia resulted in fewer altered mental status events and ICU admissions. These data favor the use of spinal anesthesia in primary THAs. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Extended Oral Antibiotic Prophylaxis After Aseptic Revision TKA: Does It Decrease Infection Risk?

BACKGROUND: Extended oral antibiotic prophylaxis (EOA) has been shown to potentially reduce infection rates after high-risk primary total knee arthroplasties (TKAs) and reimplantations. However, data is limited regarding EOA after aseptic revision TKAs. This study evaluated the impact of EOA on infection-related outcomes after aseptic revision TKAs. METHODS: 904 aseptic revision TKAs from 2014-2019 were retrospectively identified. Patients who received EOA >24 hours perioperatively (n = 267) were compared to those who did not (n = 637) using an inverse probability of treatment weighting model. Mean age was 66 years, mean BMI was 33 kg/m2, and 54% were female. Outcomes included cumulative probabilities of any infection, periprosthetic joint infection (PJI), superficial infection, and re-revision or reoperation for infection. RESULTS: The cumulative probability of any infection after aseptic revision TKA was 1.9% at 90 days, 3.5% at 1 year, and 8.1% at 5 years. Patients without EOA had a higher risk of any infection at 90 days (HR = 7.1; P = .01), but not other time points. The cumulative probability of PJI after aseptic revision TKA was 0.8% at 90 days, 2.3% at 1 year, and 6.5% at 5 years. Patients without EOA did not have an increased risk of PJI. There were no differences in re-revision or reoperation for infection at any time point between groups. CONCLUSION: Extended oral antibiotics after aseptic revision TKA were associated with a 7-fold decreased risk of any infection at 90 days. The results suggest a potential role for EOA after aseptic revision TKA and warrant additional prospective studies. LEVEL OF EVIDENCE: Level III.

Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFß1 stimulation.

Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee-related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissues from the knees of four patients undergoing primary TKAs for osteoarthritis. From these tissues, we isolated primary cells by the outgrowth method and subsequently characterized these cells in the absence and presence of the pro-myofibroblastic cytokine, transforming growth factor beta 1 (TGFß1). Light microscopy of knee outgrowth cells revealed spindle-shaped cells, and immunofluorescence (IF) analysis demonstrated staining for the fibroblast-specific markers TE-7 and vimentin (VIM). These knee outgrowth fibroblasts differentiated readily into myofibroblasts as reflected by enhanced α-smooth muscle actin (ACTA2) mRNA and protein expression and increased mRNA expression of collagen type 1 (COL1A1) and type 3 (COL3A1) with collagenous matrix deposition in the presence of TGFß1. Outgrowth knee fibroblasts were more sensitive to TGFß1-mediated myofibroblastogenesis than adipose-derived mesenchymal stromal/stem cells (MSCs). While outgrowth knee fibroblasts isolated from three anatomical regions in four patients exhibited similar gene expression, these cells are distinct from other fibroblastic cell types (i.e., Dupuytren's fibroblasts) as revealed by RNA-sequencing. In conclusion, our study provides an in vitro myofibroblastic model of outgrowth knee fibroblasts derived from patients undergoing primary TKA that can be utilized to study myofibroblastogenesis and assess therapeutic strategies for arthrofibrosis.

Outcomes of Intramedullary Nail Fixation for Metastatic Disease: Impending and Pathologic Fractures.

BACKGROUND/AIM: Intramedullary nail (IMN) fixation has become a treatment mean for impending and pathologic femur fractures. Currently there continues to be a lack of data examining functional outcomes, complications, and survivorship of patients treated with IMNs for metastatic disease of the femur. PATIENTS AND METHODS: We retrospectively identified 183 IMNs placed for impending (n=145) or pathologic (n=38) metastatic fractures from 2010 to 2018. Functional outcomes and complications including blood transfusions, venous thromboembolisms (VTEs) and reoperations were studied. RESULTS: Patients with impending lesions were more likely to be ambulatory at final follow-up (pathologic: 82%, impending: 99%, p<0.0001) and reported greater musculoskeletal tumor society scores (p<0.0001). Likewise, pathologic fractures were associated with greater discharge to non-home locations (p<0.0001) and were more likely to require a postoperative transfusion (pathologic: 66%, impending: 22%, p=0.0001). However, there was no difference in the incidence of VTEs (p=1.00) or reoperations (p=0.69) between cohorts. Patients treated for impending fractures had improved overall survival at 1 year (54% vs. 26%, p<0.0001). CONCLUSION: IMN fixation was durable in impending and pathologic femoral fractures. Early identification of metastases remains critical as patients treated for impending lesions had greater functional outcomes, fewer complications and improved survivorship compared to patients treated for pathologic fractures.

Biomechanical, histological, and molecular characterization of a new posttraumatic model of arthrofibrosis in rats.

Experimental analyses of posttraumatic knee arthrofibrosis utilize a rabbit model as a gold standard. However, a rodent model of arthrofibrosis offers many advantages including reduced cost and comparison with other models of organ fibrosis. This study aimed to characterize the biomechanical, histological, and molecular features of a novel posttraumatic model of arthrofibrosis in rats. Forty eight rats were divided into two equal groups. An immobilization procedure was performed on the right hind limbs of experimental rats. One group was immobilized for 4 weeks and the other for 8 weeks. Both groups were remobilized for 4 weeks. Limbs were studied biomechanically via assessment of torque versus degree of extension, histologically via whole knee specimen, and molecularly via gene expression of posterior capsular tissues. Significant differences were observed between experimental and control limbs at 4 N-cm of torque in the 4-week (knee extension: 115° ± 8° vs. 169° ± 17°, respectively; p = 0.007) and 8-week immobilization groups (knee extension: 99° ± 12° vs. 174° ± 9°, respectively; p = 0.008). Histologically, in each group experimental limbs demonstrated increased posterior capsular thickness and total area of tissue when compared to control limbs (p < 0.05). Gene expression values evaluated in each group were comparable. This study presents a novel rat model of arthrofibrosis with severe and persistent knee contractures demonstrated biomechanically and histologically. Statement of clinical significance: Arthrofibrosis is a common complication following contemporary total knee arthroplasties. The proposed model is reproducible, cost-effective, and can be employed for translational investigations studying the pathogenesis of arthrofibrosis and efficacy of neoadjuvant pharmacologic agents.

Triceps Tenotomy as an Alternative Exposure for Fixation of OTA/AO 13-C Fractures: A Technical Trick.

SUMMARY: Intra-articular fractures of the distal humerus present challenges to treating physician and patient alike. The olecranon osteotomy is accepted as the standard exposure for intra-articular distal humerus fractures; nevertheless, complications such as nonunion and implant prominence are common. In this article, we describe the clinical outcomes and anatomic features of the triceps tenotomy as an alternative method of exposure for internal fixation of intra-articular distal humerus fractures. The olecranon osteotomy approach affords greater exposure of the distal humerus articular surface; however, there was no difference in quality of fracture reduction, progression to fracture union, posttraumatic arthrosis, or implant failure between approaches in our series. The osteotomy approach resulted in a greater need for reoperation (15% vs. 46%, respectively); largely as a result of olecranon implant-related complications. In summary, the triceps tenotomy offers an alternative exposure for intra-articular distal humerus fracture fixation with comparable clinical outcomes to the olecranon osteotomy technique.

Comparison of free vascularized fibular flaps and allograft fibular strut grafts to supplement spinopelvic reconstruction for sacral malignancies.

AIMS: Orthopaedic and reconstructive surgeons are faced with large defects after the resection of malignant tumours of the sacrum. Spinopelvic reconstruction is advocated for resections above the level of the S1 neural foramina or involving the sacroiliac joint. Fixation may be augmented with either free vascularized fibular flaps (FVFs) or allograft fibular struts (AFSs) in a cathedral style. However, there are no studies comparing these reconstructive techniques. METHODS: We reviewed 44 patients (23 female, 21 male) with a mean age of 40 years (SD 17), who underwent en bloc sacrectomy for a malignant tumour of the sacrum with a reconstruction using a total (n = 20), subtotal (n = 2), or hemicathedral (n = 25) technique. The reconstructions were supplemented with a FVF in 25 patients (57%) and an AFS in 19 patients (43%). The mean length of the strut graft was 13 cm (SD 4). The mean follow-up was seven years (SD 5). RESULTS: There was no difference in the mean age, sex, length of graft, size of the tumour, or the proportion of patients with a history of treatment with radiotherapy in the two groups. Reconstruction using an AFS was associated with nonunion (odds ratio 7.464 (95% confidence interval (CI) 1.77 to 31.36); p = 0.007) and a significantly longer mean time to union (12 months (SD 3) vs eight (SD 3); p = 0.001) compared with a reconstruction using a FVF. Revision for a pseudoarthrosis was more likely to occur in the AFS group compared with the FVF group (hazard ratio 3.84 (95% CI 0.74 to 19.80); p = 0.109); however, this was not significant. Following the procedure, 32 patients (78%) were mobile with a mean Musculoskeletal Tumor Society Score 93 of 52% (SD 24%). There was a significantly higher mean score in patients reconstructed with a FVF compared with an AFS (62% vs 42%; p = 0.003). CONCLUSION: Supplementation of spinopelvic reconstruction with a FVF was associated with a shorter time to union and a trend towards a reduced risk of hardware failure secondary to nonunion compared with reconstruction using an AFS. Spinopelvic fixation supplemented with a FVF is our preferred technique for reconstruction following resection of a sacral tumour. Cite this article: Bone Joint J 2021;103-B(8):1414-1420.

Elevated Expression of Plasminogen Activator Inhibitor (PAI-1/SERPINE1) is Independent from rs1799889 Genotypes in Arthrofibrosis.

Arthrofibrosis is characterized by excessive extracellular matrix deposition in patients with total knee arthroplasties (TKAs) and causes undesirable joint stiffness. The pathogenesis of arthrofibrosis remains elusive and currently there are no diagnostic biomarkers for the pathological formation of this connective tissue. Fibrotic soft tissues are known to have elevated levels of plasminogen activator inhibitor-1 (PAI-1) (encoded by SERPINE1), a secreted serine protease inhibitor that moderates extracellular matrix remodeling and tissue homeostasis. The 4G/5G insertion/deletion (rs1799889) is a well-known SERPINE1 polymorphism that directly modulates PAI-1 levels. Homozygous 4G/4G allele carriers typically have higher PAI-1 levels and may predispose patients to soft tissue fibrosis (e.g., liver, lung, and kidney). Here, we examined the genetic contribution of the SERPINE1 rs1799889 polymorphism to musculoskeletal fibrosis in arthrofibrotic (n = 100) and non-arthrofibrotic (n = 100) patients using Sanger Sequencing. Statistical analyses revealed that the allele frequencies of the SERPINE1 rs1799889 polymorphism are similar in arthrofibrotic and non-arthrofibrotic patient cohorts. Because the fibrosis related SERPINE1 rs1799889 polymorphism is independent of arthrofibrosis susceptibility in TKA patients, the possibility arises that fibrosis of joint connective tissues may involve unique genetic determinants distinct from those linked to classical soft tissue fibrosis.

Acquired Idiopathic Stiffness After Contemporary Total Knee Arthroplasty: Incidence, Risk Factors, and Results Over 25 Years.

BACKGROUND: Acquired idiopathic stiffness (AIS) remains a common failure mode of contemporary total knee arthroplasties (TKAs). The present study investigated the incidence of AIS and manipulation under anesthesia (MUA) at a single institution over time, determined outcomes of MUAs, and identified risk factors associated with AIS and MUA. METHODS: We identified 9771 patients (12,735 knees) who underwent primary TKAs with cemented, modular metal-backed, posterior-stabilized implants from 2000 to 2016 using our institutional total joint registry. Mean age was 68 years, 57% were female, and mean body mass index was 33 kg/m2. Demographic, surgical, and comorbidity data were investigated via univariate Cox proportional hazard models and fit to an adjusted multivariate model to access risk for AIS and MUA. Mean follow-up was 7 years. RESULTS: During the study period, 456 knees (3.6%) developed AIS and 336 knees (2.6%) underwent MUA. Range of motion (ROM) increased a mean of 34° after the MUA; however, ROM for patients treated with MUA was inferior to patients without AIS at final follow-up (102° vs 116°, P < .0001). Significant risk factors included younger age (HR 2.3, P < .001), increased tourniquet time (HR 1.01, P < .001), general anesthesia (HR 1.3, P = .007), and diabetes (HR 1.5, P = .001). CONCLUSION: Acquired idiopathic stiffness has continued to have an important adverse impact on the outcomes of a subset of patients undergoing primary TKAs. When utilized, MUA improved mean ROM by 34°, but patients treated with MUA still had decreased ROM compared to patients without AIS. Importantly, we identified several significant risk factors associated with AIS and subsequent MUA. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

A Potential Theragnostic Regulatory Axis for Arthrofibrosis Involving Adiponectin (ADIPOQ) Receptor 1 and 2 (ADIPOR1 and ADIPOR2), TGFß1, and Smooth Muscle α-Actin (ACTA2).

(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGFß1 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle α-actin (ACTA2) at both mRNA and protein levels in basal and TGFß1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGFß-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

Contemporary Primary Total Knee Arthroplasty is Durable in Patients Diagnosed With Ankylosing Spondylitis.

INTRODUCTION: Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy affecting the axial spine and peripheral joints. Despite innovations in medical management, patients with AS experience two-fold the lifetime risk of total knee arthroplasty (TKA) compared to the general population. Moreover, recent data have indicated a correlation between spinal pathology and outcomes of TKAs. METHODS: Our institutional total joint registry identified 19 patients (28 knees) with a diagnosis of AS treated with primary TKA from 2000 to 2016. The mean age at TKA was 68 years, and 84% of patients were men. The mean follow-up period was 6 years. Outcomes included implant survivorship, clinical outcomes, and complications. RESULTS: Survivorship free from any revision was 88% at 10 years. A single patient required revision at 8 years for aseptic loosening. Survivorship free from any reoperation was 77% at 10 years. Reoperations included 2 manipulations under anesthesia and 1 superficial wound irrigation and debridement. Mean Knee Society score improved from 46 preoperatively to 89 postoperatively (P < .0001). The mean arc of motion improved from 108o preoperatively to 116° postoperatively (P = .01). There were 6 complications that did not require reoperation. CONCLUSION: Primary TKAs in patients with AS resulted in significant improvement in clinical outcomes with excellent 10-year implant survivorship. Although 2 manipulations under anesthesia were required, the range of motion was restored postoperatively. These data suggest that the contemporary primary TKA can achieve durable and reliable outcomes in patients with axial skeletal disease resulting from AS. LEVEL OF EVIDENCE: IV.