Micronized Dehydrated Human Amnion Chorion Membrane Injection in the Treatment of Knee Osteoarthritis-A Large Retrospective Case Series.

Osteoarthritis (OA) of the knee is a leading cause of chronic pain and disability in the United States. Current treatment options primarily target OA symptoms reserving surgical intervention and knee replacement for those who fail conservative measures. With average age of patients with knee OA decreasing, regenerative treatment approaches to reduce symptoms, increase quality of life, and delay the need for surgical intervention are increasingly sought. Human amniotic membrane contains growth factors and cytokines, which promote epithelial cell migration and proliferation, stimulate metabolic processes leading to collagen synthesis, and attract fibroblasts, while also reducing pain and inflammation. Micronization of the tissue allows for suspension in normal saline and injection. We conducted a retrospective review of 100 knees treated for symptomatic OA with micronized dehydrated human amnion/chorion membrane (mdHACM) and followed for 6 months. Our purpose is to present our experience and patient outcomes. Data were abstracted from electronic medical records of 82 consecutive OA patients (100 knees) injected with 100 mg mdHACM. Patient age, gender, adverse events and routinely collected Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated. Effectiveness of mdHACM treatment was measured by serial KOOS at baseline, and posttreatment at 6 weeks, 3, and 6 months. Overall mean KOOS for the cohort was 40 at baseline, improving to 52, 62, and 65 at 6 weeks, 3 months, and 6 months post-mdHACM injection. Percent increases were 32, 56, and 65%, respectively. Quality of life and sports/recreation domains improved by 111 and 118%, respectively, at 6 months. Pain scores improved by 67% at 6 months. All scores improved throughout the observation period. The most common adverse event was pain after injection lasting 2 to 7 days, observed in 68% of cases. This represents the largest single-physician experience with mdHACM for treatment of knee OA reported to date. Injectable mdHACM appears to be a potentially useful treatment option for knee OA patients. Controlled studies are underway to confirm these observations.

Direct Anterior Approach for Revision Total Hip Arthroplasty: Anatomy and Surgical Technique.

There has been increased interest and literature on the efficacy of direct anterior approach (DAA) for total hip arthroplasty (THA). Developments in surgical technique and instrumentation, along with exposure earlier in orthopaedic residency training, may augment the adoption of this approach among practicing orthopaedic surgeons. With the increasing number of primary THA performed through the DAA, understanding the indications and techniques associated with revision THA via the DAA has proved increasingly important. Patient positioning, understanding surgical anatomy and extensile maneuvers, and applying key reconstructive methods are essential for obtaining adequate exposure and fixation. Acetabular exposure can be facilitated through capsular and soft-tissue release, along with extensile approaches to the pelvis and acetabulum. Extensile distal extension can be performed for safe access to the femur, including extended femoral osteotomies. The purpose of this review is to describe indications, surgical anatomy, intraoperative tips, clinical outcomes, and complications after DAA for revision THA.

Extensile Femoral Exposure/Femoral Revision Techniques Via the Direct Anterior Approach.

The goal of this chapter is to describe the extensile femoral exposure options and femoral revision techniques using the direct anterior approach (DAA) in total hip arthroplasty. Although DAA is initially described as a muscle-sparing exposure for primary hip arthroplasty, because of its internervous anatomic dissection, the internervous and intermuscular benefits of the DAA are maintained throughout the revision exposure. This distinguishing feature of the DAA must be respected to promote maximal muscle function and stability following revision surgery. Femoral revision exposure can be challenging through any surgical approach. The direct anterior exposure provides a unique access angle to the femur and therefore the incision, releases, osteotomies, and stem insertion techniques differ in many respects from more traditional exposures. The authors hope that this chapter will expose surgeons to the cascade of revision anterior femoral exposure and demonstrate the key elements for successful revision surgery.

Accuracy of Component Positioning in 1980 Total Hip Arthroplasties: A Comparative Analysis by Surgical Technique and Mode of Guidance.

The purpose of this multi-surgeon study was to assess and compare the accuracy of acetabular component placement, leg length discrepancy (LLD), and global offset difference (GOD) between six different surgical techniques and modes of guidance in total hip arthroplasty (THA). A total of 1980 THAs met inclusion criteria. Robotic- and navigation-guided techniques were more consistent than other techniques in placing the acetabular cup into Lewinnek's safe zone (P<0.005 and P<0.05, respectively). Robotic-guided surgery was more consistent than other techniques in placing the acetabular component within Callanan's safe zone (P<0.005). No statistically significant differences were found between groups in the frequency of patients with excessive LLD. Clinically significant differences between groups were not found in the frequency of patients with excessive GOD. Level of Evidence: IV.

Hip Arthroplasty or Medical Management: A Challenging Treatment Decision for Younger Patients.

The two main treatment options for total hip arthroplasty (THA), medical management and surgical intervention, have advantages and disadvantages, creating a challenging decision. Treatment decisions are further complicated in a younger population (≤50) as the potential need for revision surgery is probable. We examined the relationship of selected variables to the decision-making process for younger patients with symptomatic OA. Thirty-five participants chose surgical intervention and 36 selected medical management for their current treatment. Pain, activity restrictions, and total WOMAC scores were statistically significant (P < .05) for patients selecting surgical intervention. No difference in quality of life was shown between groups. Pain was the only predictor variable identified, however, activity restrictions were also influential variables as these were highly correlated with pain.

Intramedullary rod and cement static spacer construct in chronically infected total knee arthroplasty.

Two-stage reimplantation, with interval antibiotic-impregnated cement spacer, is the preferred treatment of prosthetic knee joint infections. In medically compromised hosts with prior failed surgeries, the outcomes are poor. Articulating spacers in such patients render the knee unstable; static spacers have risks of dislocation and extensor mechanism injury. We examined 58 infected total knee arthroplasties with extensive bone and soft tissue loss, treated with resection arthroplasty and intramedullary tibiofemoral rod and antibiotic-laden cement spacer. Thirty-seven patients underwent delayed reimplantation. Most patients (83.8%) were free from recurrent infection at mean follow-up of 29.4 months. Reinfection occurred in 16.2%, which required debridement. Twenty-one patients with poor operative risks remained with the spacer for 11.4 months. All patients, during spacer phase, had brace-free ambulation with simulated tibiofemoral fusion, without bone loss or loss of limb length.

Intraoperative fracture during primary total knee arthroplasty.

UNLABELLED: While the occurrence of periprosthetic fractures around total knee arthroplasties (TKAs) is well know, little is known about intraoperative fractures that occur during TKA. We describe the incidence, location, and outcomes of iatrogenic intraoperative fracture during primary TKA. We reviewed 17,389 primary TKAs performed between 1985 and 2005 and identified 66 patients with 67 intraoperative fractures including 49 femur fractures, 18 tibia fractures, and no patella fractures. There were 12 men and 54 women with a mean age of 65.2 +/- 16 years. Of the 49 femur fractures, locations included medial condyle (20), lateral condyle (11), supracondylar femur (eight), medial epicondyle (seven), lateral epicondyle (two), and posterior cortex (one). Tibia fractures (18) included lateral plateau (six), anterior cortex (four), medial plateau (three), lateral cortex (three), medial cortex (one), and posterior cortex (one). Twenty-six fractures occurred during exposure and preparation, 22 while trialing, 13 during cementation, and three while inserting the polyethylene spacer. The minimum followup was 0.15 years (mean, 5.1 years; range, 0.15-15.4 years). All fractures healed clinically and radiographically. Knee Society scores and function scores improved from 46.4 and 34.6 to 79.5 and 61, respectively. Fourteen of the 66 (21%) patients were revised at an average of 2.8 years. Intraoperative fracture is an uncommon complication of primary TKA with a prevalence of 0.39%. Intraoperative fracture occurred more commonly in women (80.6%) and in the femur (73.1%). The majority of fractures occurred during exposure and bone preparation and trialing of the components. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Xanthoma of bone: a report of three cases and review of the literature.

Xanthoma of bone is a rare bone disorder characterized as a lytic lesion, often with cortical expansion or disruption. Because of its aggressive radiographic appearance, other primary bone tumors and metastatic lesions need to be ruled out. we present three cases of intraosseous xanthoma: one occurring as a pathologic fracture in the distal tibia, one discovered incidentally in the iliac crest in a patient with hip pain, and one discovered incidentally in the occipital bone of the skull in a child with widespread Hodgkin's lymphoma. All patients were treated with curettage of the lesions; craniectomy followed by cranioplasty for the occipital lesion, and curettage followed by internal fixation and bone grafting for the tibial lesion. The lesion in the iliac crest was treated with curettage and bone grafting. At the most recent follow-up (12, 15, and 24 months for patients with occipital, iliac crest, and tibial lesions, respectively), there was no evidence of local recurrence.

Periprosthetic thyroid metastasis after total knee arthroplasty: a report of two cases and review of the literature.

Total knee arthroplasty (TKA) is an attractive option for relief of pain secondary to degenerative joint disease. Overall, knee replacement surgery typically results in excellent outcomes. Nevertheless, failure caused by malalignment, infection, wear, and osteolysis is known to occur. Pain after TKA may be secondary to numerous etiologic factors-most commonly, loosening, fracture, infection, and malposition of components. This case report presents two patients who developed pain after TKA that was caused by periprosthetic thyroid metastasis and who subsequently sustained a fracture below the tibial component. Clinical and radiographic examinations, as well as surgical follow-up, are presented to underscore the need for a focused history and physical examination in the initial evaluation of a patient with a painful TKA.

Idiopathic scoliosis: identification of candidate regions on chromosome 19p13.

STUDY DESIGN: We performed genomic screening, statistical linkage analysis, and fine mapping of 202 families with at least 2 individuals with idiopathic scoliosis. OBJECTIVE: To identify regions on chromosome 19p13 statistically linked to the phenotypic expression of idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Idiopathic scoliosis is a common structural curvature of the spine affecting otherwise healthy children. Presently, no clear consensus exists regarding the underlying abnormality or genetic determinants of this disease. METHODS: Model-independent linkage analysis of qualitative and quantitative traits related to scoliosis was used to screen genotyping data from 391 markers in 202 families (1198 individuals). Subsets of families with probands having a curve > or = 30 degrees were dichotomized based on the most likely mode of inheritance for each family (autosomal dominant or X-linked dominant). Fine mapping was performed to show linkage to candidate regions on chromosome 19. RESULTS: When the threshold of disease was set at a curvature of > or = 30 degrees, qualitative linkage analysis revealed significant results at 2 successive markers on chromosome 19. CONCLUSION: The data confirm a previously reported genetic locus on chromosome 19 as potentially significant in the etiology of idiopathic scoliosis.

Dissociation of charge movement from calcium release and calcium current in skeletal myotubes by gabapentin.

The skeletal muscle L-type calcium channel or dihydropyridine receptor (DHPR) plays an integral role in excitation-contraction (E-C) coupling. Its activation initiates three sequential events: charge movement (Q(r)), calcium release, and calcium current (I(Ca,L)). This relationship suggests that changes in Q(r) might affect release and I(Ca,L). Here we studied the effect of gabapentin (GBP) on the three events generated by DHPRs in skeletal myotubes in culture. GBP specifically binds to the alpha(2)/delta(1) subunit of the brain and skeletal muscle DHPR. Myotubes were stimulated with a protocol that included a depolarizing prepulse to inactivate voltage-dependent proteins other than DHPRs. Gabapentin (50 microM) significantly increased Q(r) while decreasing the rate of rise of calcium transients. Gabapentin also reduced the maximum amplitude of the I(Ca,L) (as we previously reported) without modifying the kinetics of activation. Exposure of GBP-treated myotubes to 10 microM nifedipine prevented the increase of Q(r) promoted by this drug, indicating that the extra charge recorded originated from DHPRs. Our data suggest that GBP dissociates the functions of the DHPR from the initial voltage-sensing step and implicates a role for the alpha(2)/delta(1) subunit in E-C coupling.

Sodium current modulation by a tubulin/GTP coupled process in rat neonatal cardiac myocytes.

Microtubule disassembly by colchicine increases spontaneous beating of neonatal cardiac myocytes by an unknown mechanism. Here, we measure drug effects on spontaneous calcium transients and whole cell ionic currents to define the route between microtubule depolymerization and the increase in the rate of contraction. Colchicine treatment disassembles microtubules resulting in free tubulin dimers, thereby increasing the spontaneous beating frequency and changing both the rates of rise and decay of calcium transients. In addition, colchicine treatment produces an increase of the sodium current (I(Na)) while I(Ca) is not modified. The colchicine-enhanced I(Na) was blocked by the addition of 10 microM TTX. In addition, the colchicine-induced increase of I(Na) was prevented when GTP was omitted from the patch pipette. Vinblastine also depolymerizes microtubules but re-aggregates tubulin into paracrystalline structures. Free tubulin dimers are not increased with vinblastine treatment. We found no modification in calcium transients or I(Na) in the presence of vinblastine. Action potential durations measured at 50 % and 90 % repolarization were shorter, and the dV/dt was larger, in colchicine-treated cells compared to untreated cells. The resting membrane potential and overshoot of the action potentials were comparable in both kinds of cells. Our data suggest that release of free tubulin dimers may activate G proteins, which in turn modulate the sodium channel. An increase in whole cell I(Na) changes the spontaneous firing rate and this may be the underlying cause of the increase in the frequency of contraction in neonatal cardiac myocytes. We suggest a new role for dimeric tubulin in regulating membrane excitability.

Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury.

The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control experiments. With sham hearts, 32% of CK release was inhibited by sucrose, while 68% of the CK release was attributed to stress associated with surgery performed in the sham-septic group. In septic hearts, only 8% of the CK release was inhibited by sucrose, suggesting that more severe myocardial injury occurs when septic hearts are subjected to a calcium paradox as compared to other groups. It is evident that sucrose can inhibit a small fraction of the CK release from septic hearts during the calcium paradox as compared to the large CK loss associated with sham sepsis. We have concluded that induction of sepsis made the heart more susceptible to a calcium paradox-mediated myocardial injury.

Enhancement of L-type Ca(2+) current from neonatal mouse ventricular myocytes by constitutively active PKC-betaII.

The cardiac L-type calcium current (I(Ca)) can be modified by activation of protein kinase C (PKC). However, the effect of PKC activation on I(Ca) is still controversial. Some studies have shown a decrease in current, whereas other studies have reported a biphasic effect (an increase followed by a decrease in current or vice versa). A possible explanation for the conflicting results is that several isoforms of PKC with opposing effects on I(Ca) were activated simultaneously. Here, we examined the influence of a single PKC isoform (PKC-betaII) on L-type calcium channels in isolation from other cardiac isoforms, using a transgenic mouse that conditionally expresses PKC-betaII. Ventricular cardiac myocytes were isolated from newborn mice and examined for expression of the transgene using single cell RT-PCR after I(Ca) recording. Cells expressing PKC-betaII showed a twofold increase in nifedipine-sensitive I(Ca). The PKC-betaII antagonist LY-379196 returned I(Ca) amplitude to levels found in non-PKC-betaII-expressing myocytes. The increase in I(Ca) was independent of Ca(v)1.2-subunit mRNA levels as determined by quantitative RT-PCR. Thus these data demonstrate that PKC-beta is a potent modulator of cardiac L-type calcium channels and that this specific isoform increases I(Ca) in neonatal ventricular myocytes.