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Background Extensor mechanism disruption (EMD) combined with periprosthetic joint infection (PJI) after total knee arthroplasty are life-changing complications. The literature suggests many eventually receive above-knee amputation and lose ambulatory function. An alternative is modular knee fusion (KF), but little is known about its outcomes and biomechanical function. We report early term results on a case series of patients. Methods A retrospective review was conducted of patients who underwent 2-stage reconstruction with modular KF for combined EMD and PJI. Patient-reported outcomes at 1 year after arthrodesis and complications of surgery were recorded. Biomechanical analysis was conducted on 6 patients >1 year after surgery to measure gait speed and balance. Results Fifteen patients received a modular KF. At the most recent follow-up visit (average 25.7 months), 12 patients had their modular KFs in place and were ambulatory while 2 had died. Six patients used a walker; 4, a cane; and 2, unassisted. Gait analysis of 6 of these patients showed variation in patterns and speed. Balance was better than historical controls treated with above-knee amputation. Average Knee Injury and Osteoarthritis Outcome Score Junior was 76 ± 11. Conclusion Modular KF for EMD and PJI can result in successful outcomes in terms of preventing additional operations and maintaining ambulation. While speed is variable, physical testing shows this method for limb salvage may allow patients to ambulate with a gait aid although further studies are needed to evaluate midterm and long-term results.

Background Polyethylene liner dissociation is an uncommon complication of hip replacement. Dissociation has been associated with particular acetabular component designs. This study reviewed acetabular liner dissociations in a specific modular cup with a Morse taper locking mechanism that has not been previously reported. Methods The senior author performed 655 primary total hip arthroplasties with one particular design of acetabular component using Class A polyethylene liners and metal head articulation. Cases with revision surgery performed for acetabular liner dissociation were reviewed. Results Seven of 655 patients with this cup underwent revision surgery for a dissociated liner. Liner dissociation occurred at a mean of 73 months postoperatively. Patients presented with new-onset hip pain or squeaking, 4 of which developed symptoms acutely. Two patients treated with polyethylene liner exchange into the same cup required a second revision surgery for recurrent dissociation. Conclusion Polyethylene liner dissociation is an infrequent but possible complication associated with modular acetabular components using a Morse taper locking. Providers should be vigilant with long-term follow-up of patients with this acetabular system for patient complaints of catching or squeaking. Patients treated for liner dissociation should not have a new liner placed into the same acetabular shell given the risk for further dissociation.

Introduction: Management of periprosthetic infection in total hip arthroplasties is challenging, especially when there is severe loss of proximal femoral bone stock. When a 2-stage approach is used, either a static or an articulating spacer may be considered. Static spacers leave the patient with a flail leg, which can be very difficult with massive bone loss. The purpose of this study is to report a novel technique for articulating antibiotic spacers and report our results. Materials and Methods: We describe a technique for an articulating hip spacer in the setting of a large amount of proximal femoral bone loss using a locked intramedullary nail, modular femoral body, and an all-polyethylene constrained acetabular component. This technique allowed for mobilization of the patient without a flail leg. Four patients underwent 2-stage reconstruction, and the case series is reported here. Results: No complications occurred due to the spacer, and in all cases, a second reconstruction was later carried out after treatment with intravenous antibiotics. Three of 4 patients did well after 2-stage reconstruction, with 1 patient ultimately requiring an amputation. Discussion: We feel this technique improves upon previously reported large spacers due to the stability and maintenance of leg length. Conclusion: This technique offers a modular solution to address massive bone loss of the proximal femur in the face of periprosthetic joint infection.

Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action, wild-type (sod2(+/+)) and heterozygous knockout mice (sod2(+/-)) were fed a chow or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin action in vivo. GSIS during HG clamps was equal in chow-fed sod2(+/-) and sod2(+/+) but was markedly decreased in HF-fed sod2(+/-). Remarkably, this impairment was not paralleled by reduced HG glucose infusion rate (GIR). Decreased GSIS in HF-fed sod2(+/-) was associated with increased ROS, such as superoxide ion. Surprisingly, insulin action determined by HI clamps did not differ between sod2(+/-) and sod2(+/+) of either diet. Since insulin action was unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2(+/-) was due to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho-AMPK protein in muscle of HF-fed sod2(+/-) support this hypothesis. We conclude that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes observed in diabetic humans, impairs GSIS in HF-fed mice without affecting insulin action.

Increased deposition of specific extracellular matrix (ECM) components is a characteristic of insulin-resistant skeletal muscle. Hyaluronan (HA) is a major constituent of the ECM. The hypotheses that 1) HA content is increased in the ECM of insulin-resistant skeletal muscle and 2) reduction of HA in the muscle ECM by long-acting pegylated human recombinant PH20 hyaluronidase (PEGPH20) reverses high-fat (HF) diet–induced muscle insulin resistance were tested. We show that muscle HA was increased in HF diet–induced obese (DIO) mice and that treatment of PEGPH20, which dose-dependently reduced HA in muscle ECM, decreased fat mass, adipocyte size, and hepatic and muscle insulin resistance in DIO mice at 10 mg/kg. Reduced muscle insulin resistance was associated with increased insulin signaling, muscle vascularization, and percent cardiac output to muscle rather than insulin sensitization of muscle per se. Dose-response studies revealed that PEGPH20 dose-dependently increased insulin sensitivity in DIO mice with a minimally effective dose of 0.01 mg/kg. PEGPH20 at doses of 0.1 and 1 mg/kg reduced muscle HA to levels seen in chow-fed mice, decreased fat mass, and increased muscle glucose uptake. These findings suggest that ECM HA is a target for treatment of insulin resistance.

We determined whether: (1) an acute lipid infusion impairs skeletal muscle AMP-activated protein kinase (AMPK)α2 activity, increases inducible nitric oxide synthase (iNOS) and causes peripheral insulin resistance in conscious, unstressed, lean mice; and (2) restoration of AMPKα2 activity during the lipid infusion attenuates the increase in iNOS and reverses the defect in insulin sensitivity in vivo.Chow-fed, 18-week-old C57BL/6J male mice were surgically catheterised. After 5 days they received: (1) a 5 h infusion of 5 ml kg(-1) h(-1) Intralipid + 6 U/h heparin (Lipid treatment) or saline (Control); (2) Lipid treatment or Control, followed by a 2 h hyperinsulinaemic-euglycaemic clamp (insulin clamp; 4 mU kg(-1) min(-1)); and (3) infusion of the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) (1 mg kg(-1) min(-1)), or saline during Lipid treatment, followed by a 2 h insulin clamp. In a separate protocol, mice producing a muscle-specific kinase-dead AMPKα2 subunit (α2-KD) underwent an insulin clamp to determine the role of AMPKα2 in insulin-mediated muscle glucose metabolism.Lipid treatment decreased AMPKα2 activity, increased iNOS abundance/activation and reduced whole-body insulin sensitivity in vivo. AICAR increased AMPKα2 activity twofold; this did not suppress iNOS or improve whole-body or tissue-specific rates of glucose uptake during Lipid treatment. AICAR caused a marked increase in insulin-mediated glycogen synthesis in skeletal muscle. Consistent with this latter result, lean α2-KD mice exhibited impaired insulin-stimulated glycogen synthesis even though muscle glucose uptake was not affected.Acute induction of insulin resistance via lipid infusion in healthy mice impairs AMPKα2, increases iNOS and causes insulin resistance in vivo. However, these changes do not appear to be interrelated. Rather, a functionally active AMPKα2 subunit is required for insulin-stimulated muscle glycogen synthesis.

Metal hypersensitivity has been an identified problem in orthopedics for nearly half a century, but its implications remain unclear. Establishing which total joint arthroplasty (TJA) candidates may do poorly with conventional implants and which patients would benefit from revision to an allergen-free implant remains challenging. Our systematic search of the MEDLINE database identified 52 articles for inclusion in our review. Case reports revealed that half of patients presented with pain and swelling, while only one-third presented with cutaneous symptoms. All patients were symptomatic within the first post-operative year; 90% were symptomatic within 3 months. Reports of patch testing revealed that patients with TJAs were positive for metal sensitivity more often than patients without TJAs (OR 1.3). Those with poorly functioning arthroplasties and those who had already had revisions tested positive more often than those with well-functioning TJAs (OR 1.7) and those without TJAs (OR 3.1). Lymphocyte transformation testing (LTT) shows promise in diagnosing metal allergy, and components of bone cement are also being recognized as potential allergens. Further work is necessary to delineate which patients should be tested for metal allergy and which patients would benefit from allergen-free implants.

Increased extracellular matrix (ECM) collagen is a characteristic of muscle insulin resistance. Matrix metalloproteinase (MMP) 9 is a primary enzyme that degrades collagen IV (ColIV). As a component of the basement membrane, ColIV plays a key role in ECM remodelling. We tested the hypotheses that genetic deletion of MMP9 in mice increases muscle ColIV, induces insulin resistance in lean mice and worsens diet-induced muscle insulin resistance.Wild-type (Mmp9(+/+)) and Mmp9-null (Mmp9(-/-)) mice were chow or high-fat (HF) fed for 16 weeks. Insulin action was measured by the hyperinsulinaemic-euglycaemic clamp in conscious weight-matched surgically catheterised mice.Mmp9(-/-) and HF feeding independently increased muscle ColIV. ColIV in HF-fed Mmp9(-/-) mice was further increased. Mmp9(-/-) did not affect fasting insulin or glucose in chow- or HF-fed mice. The glucose infusion rate (GIR), endogenous glucose appearance (EndoRa) and glucose disappearance (Rd) rates, and a muscle glucose metabolic index (Rg), were the same in chow-fed Mmp9(+/+) and Mmp9(-/-) mice. In contrast, HF-fed Mmp9(-/-) mice had decreased GIR, insulin-stimulated increase in Rd and muscle Rg. Insulin-stimulated suppression of EndoRa, however, remained the same in HF-fed Mmp9(-/-) and Mmp9(+/+) mice. Decreased muscle Rg in HF-fed Mmp9(-/-) was associated with decreased muscle capillaries.Despite increased muscle ColIV, genetic deletion of MMP9 does not induce insulin resistance in lean mice. In contrast, this deletion results in a more profound state of insulin resistance, specifically in the skeletal muscle of HF-fed mice. These results highlight the importance of ECM remodelling in determining muscle insulin resistance in the presence of HF diet.

The objective of this study was to test the hypothesis that exercise-stimulated muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive oxygen species (mtROS) scavenging capacity. This hypothesis was tested in genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS formation. Mice overexpressing SOD2 ( sod2Tg), mitochondria-targeted catalase ( mcatTg), and combined SOD2 and mCAT (mtAO) were used to increase mtROS scavenging. mtROS was assessed by the H2O2 emitting potential ( JH2O2) in muscle fibers. sod2Tg did not decrease JH2O2 in chow-fed mice, but decreased JH2O2 in HF-fed mice. mcatTg and mtAO decreased JH2O2 in both chow- and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione (GSH/GSSG) was unaltered in sod2Tg in chow-fed mice, but was increased in HF-fed sod2Tg and both chow- and HF-fed mcatTg and mtAO. Nitrotyrosine, a marker of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was decreased in both chow- and HF-fed sod2Tg, mcatTg, and mtAO mice. This effect was not changed with exercise. Kg, an index of MGU was assessed using 2-[14C]-deoxyglucose during exercise. In chow-fed mice, sod2Tg, mcatTg, and mtAO increased exercise Kg compared with wild types. Exercise Kg was also augmented in HF-fed sod2Tg and mcatTg mice but unchanged in HF-fed mtAO mice. In conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this regulation depends on nutritional state.

Objective Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. Design C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high fat (HF) diets from 3–16 weeks (wks) of age. At 15wks mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16wks. In a separate study, HF-fed WT and α2-KD mice performed 5wks of exercise training (from 15–20wks of age) to test whether AMPKα2 is necessary to restore work tolerance. Results HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (p