Quality indicators for osteoarthritis pain management in the primary care setting.

BACKGROUND: Development of valid and feasible quality indicators (QIs) is needed to track quality initiatives for osteoarthritis pain management in primary care settings. METHODS: Literature search identified published guidelines that were reviewed for QI extraction. A panel of 14 experts was assembled, including primary care physicians, rheumatologists, orthopedic surgeons, pain specialists, and outcomes research pharmacists. A screening survey excluded QIs that cannot be reliably extracted from the electronic health record or that are irrelevant for osteoarthritis in primary care settings. A validity screening survey used a 9-point Likert scale to rate the validity of each QI based on predefined criteria. During expert panel discussions, stakeholders revised QI wording, added new QIs, and voted to include or exclude each QI. A priority survey used a 9-point Likert scale to prioritize the included QIs. RESULTS: Literature search identified 520 references published from January 2015 to March 2021 and 4 additional guidelines from professional/governmental websites. The study included 41 guidelines. Extraction of 741 recommendations yielded 115 candidate QIs. Feasibility screening excluded 28 QIs. Validity screening and expert panel discussion excluded 73 QIs and added 1 QI. The final set of 15 prioritized QIs focused on pain management safety, education, weight-management, psychological wellbeing, optimizing first-line medications, referral, and imaging. CONCLUSION: This multi-disciplinary expert panel established consensus on QIs for osteoarthritis pain management in primary care settings by combining scientific evidence with expert opinion. The resulting list of 15 prioritized, valid, and feasible QIs can be used to track quality initiatives for osteoarthritis pain management.

Innovation for Orthopaedic Surgeons.

Entrepreneurship and innovation are cornerstones of the economy and move healthcare forward. Most physicians have little experience or knowledge in developing and commercializing novel concepts and ideas. It is important to focus on structured thinking concepts, fundraising, intellectual property, FDA regulations, and initial incorporation and teambuilding strategies. There are various aspects of creating ideas and moving them from notes scribbled on a napkin to a product or service, which can then be integrated into the economic fabric of the healthcare system. Surgeon founders and innovators can then share key aspects any surgeon should consider when becoming an entrepreneur.

Increased fracture risk and low bone mineral density in patients with loeys-dietz syndrome.

Loeys-Dietz syndrome is a recently recognized connective tissue disorder with widespread systemic involvement. Little is known about its skeletal phenotype. Our goal was to investigate the risk of fracture and incidence of low bone mineral density in patients with Loeys-Dietz syndrome. We performed a cross-sectional, descriptive, survey-based study with subsequent chart review from July 2011 to April 2012. Fifty-seven patients (26 men, 31 women) with Loeys-Dietz syndrome confirmed by genetic testing completed the survey (average age, 25.3 years; range, 0.9-79.6 years). There were a total of 51 fractures (33 patients): 35 fractures in the upper extremities, 14 in the lower extremities, and two in the spine. Fourteen patients (24.6%) reported two or more fractures. There was a 50% risk of fracture by age 14 years. The incidence of any fracture in this cohort was 3.86 per 100 person-years. Seventeen patients had dual-energy X-ray absorptiometry scans available for review, 11 (64.7%) of whom had at least one fracture. Thirteen included lumbar spine absorptiometry reports; eight (61.5%) indicated low or very low bone mineral density. In the left hip, ten of 14 participants (71.4%) had low or very low bone mineral density. In the left femoral neck, nine of 13 participants (69.2%) had low or very low bone mineral density. The lowest Z- and T-scores were not associated with an increased number of fractures. Patients with Loeys-Dietz syndrome have a high risk of fracture and a high incidence of low bone mineral density.

Intraarticular abnormalities in overhead athletes are variable.

BACKGROUND: The cause of shoulder pain and dysfunction in the overhead athlete can be variable. Several studies illustrate the wide variety of lesions seen at the time of arthroscopy in overhead athletes who require surgery but it is unclear whether these differ by sport. QUESTIONS/PURPOSES: We examined overhead athletes with shoulder dysfunction to determine (1) the range of arthroscopically visualized shoulder abnormalities with specific attention to the posterosuperior glenohumeral joint and the rotator cuff; and (2) the relationship of sport type to these abnormalities. METHODS: We reviewed our institution's database for professional and collegiate athletes in overhead sports who, from 1996 through 2010, had diagnostic shoulder arthroscopy for insidious, nontraumatic, persistent pain and inability to participate in their sport. A descriptive analysis of the arthroscopic findings from 51 consecutive patients (33 males, 18 females; mean age, 25 years; range, 15-59 years) was done. We analyzed the arthroscopic findings with respect to sport using analysis of variance and Fisher's exact test. RESULTS: There was a wide range of superior labrum, posterosuperior glenoid, and rotator cuff abnormalities. Overall, the most frequent abnormalities were posterosuperior glenohumeral joint changes. Swimmers had fewer intraarticular abnormalities than baseball players. CONCLUSIONS: We found a wide spectrum of intraarticular abnormalities in the shoulder of overhead athletes with shoulder pain requiring surgery. Additional study is needed to determine whether these abnormalities or combinations relate to specific athletic movements. LEVEL OF EVIDENCE: Level IV, retrospective case series. See Guidelines for Authors for a complete description of levels of evidence.

Allopurinol-induced DRESS syndrome in an adolescent patient.

A 16-year-old male patient, with a history of essential hypertension enrolled in an experimental drug protocol using allopurinol, presented to our emergency department with a 10-day history of fever. Initial laboratory evaluation revealed leukocytosis, eosinophilia, and transaminitis. After extensive work-up and exclusion of infectious and oncologic etiologies, the diagnosis of allopurinol-induced drug reaction and eosinophilia with systemic symptoms syndrome was carried out. The patient responded to administration of IV methylprednisolone, with complete resolution of symptoms and improvement of laboratory abnormalities. This case represents the first report of allopurinol-induced drug reaction and eosinophilia with systemic symptoms syndrome in a pediatric patient.

Implant durability and knee function after total knee arthroplasty in the morbidly obese patient.

This study investigated the effect of body mass index (BMI) on outcomes after cemented tricompartmental total knee arthroplasty (TKA). Functional and radiographic Knee Society scores in 71 patients (94 knees) with BMI 30 to 39 and 31 patients (41 knees) with BMI > or =40 were compared with 67 patients (85 knees) with BMI 20 to 29 at a mean follow-up of 5.4 years. Total knee arthroplasty rates of success (79%), complication (17%), and revision (6%) were independent of BMI. The BMI > or =40 group, however, was 5.4x (95% confidence interval, 2.1-14.7) more likely to develop patellar radiolucencies, had poorer hamstring and quadriceps conditioning, and had more patellofemoral symptoms. Forty percent of TKAs at BMI > or =40 with patellar radiolucencies failed. In conclusion, TKA benefits were realized at all BMI, but at BMI > or =40, more rehabilitation and monitoring are recommended.

Mechanical Properties and Microstructural Collagen Alignment of the Ulnar Collateral Ligament During Dynamic Loading.

BACKGROUND: The ulnar collateral ligament (UCL) microstructural organization and collagen fiber realignment in response to load are unknown. PURPOSE/HYPOTHESIS: The purpose was to describe the real-time microstructural collagen changes in the anterior bundle (AB) and posterior bundle (PB) of the UCL with tensile load. It was hypothesized that the UCL AB is stronger and stiffer with more highly aligned collagen during loading when compared with the UCL PB. STUDY DESIGN: Descriptive laboratory study. METHODS: The AB and PB from 34 fresh cadaveric specimens were longitudinally sectioned to allow uniform light passage for quantitative polarized light imaging. Specimens were secured to a tensile test machine and underwent cyclic preconditioning, a ramp-and-hold stress-relaxation test, and a quasi-static ramp to failure. A division-of-focal-plane polarization camera captured real-time pixelwise microstructural data of each sample during stress-relaxation and at the zero, transition, and linear points of the stress-strain curve. The SD of the angle of polarization determined the deviation of the average direction of collagen fibers in the tissue, while the average degree of linear polarization evaluated the strength of collagen alignment in those directions. Since the data were nonnormally distributed, the median ± interquartile range are presented. RESULTS: The AB has larger elastic moduli than the PB ( P < .0001) in the toe region (median, 2.73 MPa [interquartile range, 1.1-5.6 MPa] vs 0.65 MPa [0.44-1.5 MPa]) and the linear region (13.77 MPa [4.8-40.7 MPa] vs 1.96 MPa [0.58-9.3 MPa]). The AB demonstrated larger stress values, stronger collagen alignment, and more uniform collagen organization during stress-relaxation. PB collagen fibers were more disorganized than the AB during the zero ( P = .046), transitional ( P = .011), and linear ( P = .007) regions of the stress-strain curve. Both UCL bundles exhibited very small changes in collagen alignment (SD of the angle of polarization) with load. CONCLUSION: The AB of the UCL is stiffer and stronger, with more strongly aligned and more uniformly oriented collagen fibers, than the PB. The small changes in collagen alignment indicate that the UCL response to load is due more to its static collagen organization than to dynamic changes in collagen alignment. CLINICAL RELEVANCE: The UCL collagen organization may explain its susceptibility to injury with repetitive valgus loads.

Factors Affecting Perceptions of Open, Mini-Open, and Arthroscopic Rotator Cuff Repair Techniques Among Medical Professionals.

Although no long-term difference between arthroscopic and mini-open rotator cuff repairs has been documented, use of arthroscopic repair has exploded. We conducted a study to determine which repair technique medical professionals preferred for their own surgery and to analyze the perceptions shaping those opinions. A survey was emailed to selected professionals at our institution: attendings, residents, and allied health professionals; 84 (41, 20, and 23, respectively) responded. Irrespective of specialty or career length, almost half (39, 46%) preferred deferring the repair choice to their surgeon; the other 45 preferred arthroscopic (22, 26%), mini-open (19, 23%), open (2, 2%), or no (2, 2%) repair. Most agreed repairs were safe and fast but had no opinion about cost-effectiveness or which technique provided the best outcome. Significantly (P < .05) more respondents thought arthroscopic and mini-open repairs promoted quick healing, good cosmetic results, and patient satisfaction compared with open repair, but these repairs were also perceived as significantly (P < .05) harder to learn and more challenging than open repair. It is important for medical professionals to recognize these biases, especially given that many defer to the judgment of their medical peers.

Dysregulated TGF-ß signaling alters bone microstructure in a mouse model of Loeys-Dietz syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular and skeletal abnormalities resembling Marfan syndrome, including a predisposition for pathologic fracture. LDS is caused by heterozygous mutations in the genes encoding transforming growth factor-ß (TGF-ß) type 1 and type 2 receptors. In this study, we characterized the skeletal phenotype of mice carrying a mutation in the TGF-ß type 2 receptor associated with severe LDS in humans. Cortical bone in LDS mice showed significantly reduced tissue area, bone area, and cortical thickness with increased eccentricity. However, no significant differences in trabecular bone volume were observed. Dynamic histomorphometry performed in calcein-labeled mice showed decreased mineral apposition rates in cortical and trabecular bone with normal numbers of osteoblasts and osteoclasts. Mechanical testing of femurs by three-point bending revealed reduced femoral strength and fracture resistance. In vitro, osteoblasts from LDS mice demonstrated increased mineralization with enhanced expression of osteoblast differentiation markers compared with control cells. These changes were associated with impaired TGF-ß1-induced Smad2 and Erk1/2 phosphorylation and upregulated TGF-ß1 ligand mRNA expression, compatible with G357W as a loss-of-function mutation in the TGF-ß type 2 receptor. Paradoxically, phosphorylated Smad2/3 in cortical osteocytes measured by immunohistochemistry was increased relative to controls, possibly suggesting the cross-activation of TGF-ß-related receptors. The skeletal phenotype observed in the LDS mouse closely resembles the principal structural features of bone in humans with LDS and establishes this mouse as a valid in vivo model for further investigation of TGF-ß receptor signaling in bone.

Effects of ketamine/xylazine on expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and cyclo-oxygenase-2 in rat gastric mucosa during endotoxemia.

Some anesthetics attenuate expression of endotoxin-induced production of proinflammatory genes. The anesthetic combination of ketamine/xylazine (K/X) decreases lipopolysaccharide (LPS)-induced liver injury in rats. However, the effects of K/X on gut function and gene expression are unknown. The purpose of this study was to examine the effect of K/X on LPS-induced gastric fluid accumulation, and gastric tumor necrosis factor (TNF)-alpha, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase (COX)-2 expression, as well as serum TNF-alpha protein levels over time. We hypothesized that K/X would attenuate these LPS-induced endpoints. Rats were given either intraperitoneal saline or K (70 mg/kg) and X (6 mg/kg) 1 h before saline or LPS (20 mg/kg i.p.) treatment of 1, 3, or 5 h. Serum and gastric fluid and mucosa were collected and TNF-alpha, iNOS, and COX-2 expression were determined. LPS caused a significant increase in early serum and gastric mucosal TNF-alpha protein expression at 1 h, an effect that was significantly attenuated by K/X pretreatment. LPS caused significant gastric stasis and increased iNOS and COX-2 mRNA expression and iNOS protein expression in the stomach when compared with controls. K/X attenuated LPS-induced gastric fluid accumulation and upregulation of iNOS mRNA and protein, but not COX-2. These data indicate that K/X inhibits some proinflammatory genes and pathophysiologic responses in the serum and stomach during endotoxemia. The effects of K/X appear to inhibit transcriptional events in iNOS expression, which may be dependent on K/X-induced inhibition of early TNF-alpha expression. Furthermore, in rat models of endotoxemia, especially those evaluating the stomach, careful consideration needs to be given if anesthetic combinations with ketamine and/or xylazine are used, as they alter LPS-induced responses.

Evolution of autologous chondrocyte repair and comparison to other cartilage repair techniques.

UNLABELLED: Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. METHODS: We searched PubMed from 1949 to 2014 for the keywords "autologous chondrocyte implantation" (ACI) and "cartilage repair" in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. RESULTS: Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells) and associated scaffolds (natural or synthetic, hydrogels or membranes). ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient's knee as evaluated by multiple clinical indices and the quality of regenerated tissue. CONCLUSION: Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

MRI of the elbow: techniques and spectrum of disease: AAOS exhibit selection.

BACKGROUND: Magnetic resonance imaging (MRI) of the elbow allows for high-resolution evaluation of osseous and soft-tissue structures, including ligaments, tendons, nerves, and muscles. Multiple imaging techniques and pulse sequences exist. The purpose of this article is to update orthopaedic surgeons on current MRI techniques and illustrate the spectrum of elbow pathology detectable by MRI. METHODS: We searched MEDLINE with use of the keywords "MRI" and "elbow" for studies less than five years old evaluating MRI techniques. These papers, our experience, and textbooks reviewing elbow MRI provided the information for this article. RESULTS: We discuss the essentials and applications of the following techniques: (1) conventional, non-gadolinium-enhanced MRI; (2) gadolinium-enhanced MRI; and (3) magnetic resonance arthrography. The classic MRI appearances of occult fractures, loose bodies, ulnar collateral ligament injuries, lateral collateral ligament complex injuries, biceps tendon injuries, triceps tendon injuries, lateral epicondylitis, medial epicondylitis, septic arthritis, osteomyelitis, osteochondritis dissecans, compression neuropathies, synovial disorders, and various soft-tissue masses are reviewed. CONCLUSIONS: MRI is a valuable, noninvasive method of elbow evaluation. This article updates orthopaedic surgeons on the various available MRI techniques and facilitates recognition of the MRI appearances of the most commonly seen pathologic elbow conditions.

An injectable method for noninvasive spine fusion.

BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) induce bone formation but are difficult to localize, and subsequent diffusion from the site of interest and short half-life reduce the efficacy of the protein. Currently, spine fusion requires stripping, decortications of the transverse processes, and an autograft harvest procedure. Even in combination with BMPs, clinical spinal fusion has a high failure rate, presumably because of difficulties in localizing sufficient levels of BMP. PURPOSE: The goal was to achieve reliable spine fusion through a single injection of a cell-based gene therapy system without the need for any surgical intervention. STUDY DESIGN: Eighty-seven immunodeficient (n=44) and immune-competent (n=43) mice were injected along the paraspinous musculature to achieve rapid induction of heterotopic ossification (HO) and ultimately spinal arthrodesis. METHODS: Immunodeficient and immune-competent mice were injected with fibroblasts, transduced with an adenoviral vector to express BMP2, along the paraspinous musculature. Bone formation was evaluated via radiographs, microcomputed tomography, and biomechanical analysis. RESULTS: ew bridging bone between the vertebrae and the fusion to adjacent skeletal bone was obtained as early as 2 weeks. Reduction in spine flexion-extension also occurred as early as 2 weeks after injection of the gene therapy system, with greater than 90% fusion by 4 weeks in all animals regardless of their genetic background. CONCLUSIONS: Injection of our cell-based system into the paraspinous musculature induces spinal fusion that is dependent neither on the cell type nor on the immune status. These studies are the first to harness HO in an immune-competent model as a noninvasive injectable system for clinically relevant spinal fusion and may one day impact human spinal arthrodesis.

Assessing mechanical integrity of spinal fusion by in situ endochondral osteoinduction in the murine model.

BACKGROUND: Historically, radiographs, micro-computed tomography (micro-CT) exams, palpation and histology have been used to assess fusions in a mouse spine. The objective of this study was to develop a faster, cheaper, reproducible test to directly quantify the mechanical integrity of spinal fusions in mice. METHODS: Fusions were induced in ten mice spine using a previously described technique of in situ endochondral ossification, harvested with soft tissue, and cast in radiolucent alginate material for handling. Using a validated software package and a customized mechanical apparatus that flexed and extended the spinal column, the amount of intervertebral motion between adjacent vertebral discs was determined with static flexed and extended lateral spine radiographs. Micro-CT images of the same were also blindly reviewed for fusion. RESULTS: Mean intervertebral motion between control, non-fused, spinal vertebral discs was 6.1 +/- 0.2 degrees during spine flexion/extension. In fusion samples, adjacent vertebrae with less than 3.5 degrees intervertebral motion had fusions documented by micro-CT inspection. CONCLUSIONS: Measuring the amount of intervertebral rotation between vertebrae during spine flexion/extension is a relatively simple, cheap (<$100), clinically relevant, and fast test for assessing the mechanical success of spinal fusion in mice that compared favorably to the standard, micro-CT.

Role of the C-terminus of the high-conductance calcium-activated potassium channel in channel structure and function.

The role of ion channels in cell physiology is regulated by processes occurring after protein biosynthesis, which are critical for both channel function and targeting of channels to appropriate cell compartments. Here we apply biochemical and electrophysiological methods to investigate the role of the high-conductance, calcium-activated potassium (Maxi-K) channel C-terminal domain in channel tetramerization, association with the beta1 subunit, trafficking of the channel complex to the cell surface, and channel function. No evidence for channel tetramerization, cell surface expression, or function was observed with Maxi-K(1)(-)(323), a construct truncated three residues after the S(6) transmembrane domain. However, Maxi-K(1)(-)(343) and Maxi-K(1)(-)(441) are able to form tetramers and to associate with the beta1 subunit. Maxi-K(1)(-)(343)-beta1 and Maxi-K(1)(-)(441)-beta1 complexes are efficiently targeted to the cell surface and cannot be pharmacologically distinguished from full-length channels in binding experiments but do not form functional channels. Maxi-K(1)(-)(651) forms tetramers and associates with beta1; however, the complex is not present at the cell surface, but is retained intracellularly. Maxi-K(1)(-)(651) surface expression and channel function can be fully rescued after coexpression with its C-terminal complement, Maxi-K(652)(-)(1113). However coexpression of Maxi-K(1)(-)(343) and Maxi-K(1)(-)(441) with their respective C-terminal complements did not rescue channel function. Together, these data demonstrate that the domain(s) in the Maxi-K channel necessary for formation of tetramers, coassembly with the beta1 subunit, and cell surface expression resides within the S(0)-S(6) linker domain of the protein, and that structural constraints within the gating ring in the C-terminal region can regulate trafficking and function of constructs truncated in this region.

Ketamine/xylazine attenuates LPS-induced iNOS expression in various rat tissues.

Ketamine and xylazine (K/X) are commonly used in combination as an anesthetic agent in experimental animal models. We previously noted that K/X attenuated lipopolysaccharide (LPS)-induced liver injury, gastric stasis, and reduced symptoms of endotoxemia. Because ketamine attenuates expression of several proinflammatory genes, we examined the effects of K/X on inducible nitric oxide synthase (iNOS), which has been implicated in endotoxin-induced tissue injury. We hypothesized that K/X would attenuate LPS-induced expression of iNOS in various organs in the rat. Rats were given either intraperitoneal saline or ketamine (70 mg/kg) and xylazine (6 mg/kg) 1 h before saline or LPS (20 mg/kg). Rats were sacrificed 5 h later and stomach, duodenum, jejunum, ileum, colon, liver, lung, kidney, and spleen were collected for determination of iNOS protein immunoreactivity by Western immunoblot. Data reported in densitometric units (DU) as mean +/- SEM (n >/= 5; ANOVA). LPS significantly increased iNOS protein immunoreactivity in all tissues examined versus saline controls (P