Hospital for Special Surgery

A new total knee rating system has been developed by The Knee Society to provide an up-to-date more stringent evaluation form. The system is subdivided into a knee score that rates only the knee joint itself and a functional score that rates the patient's ability to walk and climb stairs. The dual rating system eliminates the problem of declining knee scores associated with patient infirmity.

Wound healing is an evolutionarily conserved, complex, multicellular process that, in skin, aims at barrier restoration. This process involves the coordinated efforts of several cell types including keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets. The migration, infiltration, proliferation, and differentiation of these cells will culminate in an inflammatory response, the formation of new tissue and ultimately wound closure. This complex process is executed and regulated by an equally complex signaling network involving numerous growth factors, cytokines and chemokines. Of particular importance is the epidermal growth factor (EGF) family, transforming growth factor beta (TGF-beta) family, fibroblast growth factor (FGF) family, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor (GM-CSF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), interleukin (IL) family, and tumor necrosis factor-alpha family. Currently, patients are treated by three growth factors: PDGF-BB, bFGF, and GM-CSF. Only PDGF-BB has successfully completed randomized clinical trials in the Unites States. With gene therapy now in clinical trial and the discovery of biodegradable polymers, fibrin mesh, and human collagen serving as potential delivery systems other growth factors may soon be available to patients. This review will focus on the specific roles of these growth factors and cytokines during the wound healing process.

Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1). Often OA is referred to as degenerative joint disease “(DJD)”. This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint. The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3). Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function. The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule. There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA. The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure”. In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues. Open in a separate window Figure 1 Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis. (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow). Image courtesy of Drs. Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

BACKGROUND: Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. METHODS: We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. RESULTS: Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. CONCLUSIONS: Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)

Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health. Figure 1. Gross photograph of healthy articular cartilage in an adult human knee. Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

OBJECTIVE: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. RESULTS: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. CONCLUSION: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.

BACKGROUND: The volume of primary total joint arthroplasty (TJA) procedures has risen in recent decades. However, recent procedure growth has not been at previously projected exponential rates. To anticipate the future expense of TJA, updated models are necessary to predict TJA volume in the U.S. METHODS: Retrospective review using the National Inpatient Sample, a representative sample of all hospital discharges within the U.S., was employed to determine the volume of primary TJA procedures performed from 2000 to 2014. Over 116 million discharge records were reviewed and weighted to determine the simulated annual TJA volume. The annual incidence rate of each procedure was determined by combining procedure volume with annual census data among the overall population and in subpopulations defined by sex and age. Linear and Poisson regression analyses were performed to determine the projected future volume of TJA procedures. Subanalysis with linear regression estimates based on 2000 to 2008 and 2008 to 2014 growth rates was performed. RESULTS: On the basis of 2000-to-2014 data, primary total hip arthroplasty (THA) is projected to grow 71%, to 635,000 procedures, by 2030 and primary total knee arthroplasty (TKA) is projected to grow 85%, to 1.26 million procedures, by 2030. However, TKA procedure growth rate has been slowing over recent years, and models based on 2008-to-2014 data projected growth to only approximately 935,000 procedures by 2030. CONCLUSIONS: Previously anticipated exponential TJA growth is inconsistent with the most recent trends. An updated projection based on 2000-to-2014 data is provided to project the growth of primary TJA procedures to the year 2030. These data will help guide health-care economic policy and allocation of future resources in order to optimize the delivery of patient care.

During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.

BACKGROUND: Etanercept, which blocks the action of tumor necrosis factor, reduces disease activity in patients with long-standing rheumatoid arthritis. Its efficacy in reducing disease activity and preventing joint damage in patients with active early rheumatoid arthritis is unknown. METHODS: We treated 632 patients with early rheumatoid arthritis with either twice-weekly subcutaneous etanercept (10 or 25 mg) or weekly oral methotrexate (mean, 19 mg per week) for 12 months. Clinical response was defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology. Bone erosion and joint-space narrowing were measured radiographically and scored with use of the Sharp scale. On this scale, an increase of 1 point represents one new erosion or minimal narrowing. RESULTS: As compared with patients who received methotrexate, patients who received the 25-mg dose of etanercept had a more rapid rate of improvement, with significantly more patients having 20 percent, 50 percent, and 70 percent improvement in disease activity during the first six months (P<0.05). The mean increase in the erosion score during the first 6 months was 0.30 in the group assigned to receive 25 mg of etanercept and 0.68 in the methotrexate group (P= 0.001), and the respective increases during the first 12 months were 0.47 and 1.03 (P=0.002). Among patients who received the 25-mg dose of etanercept, 72 percent had no increase in the erosion score, as compared with 60 percent of patients in the methotrexate group (P=0.007). This group of patients also had fewer adverse events (P=0.02) and fewer infections (P= 0.006) than the group that was treated with methotrexate. CONCLUSIONS: As compared with oral methotrexate, subcutaneous [corrected] etanercept acted more rapidly to decrease symptoms and slow joint damage in patients with early active rheumatoid arthritis.

A method for deriving a more convenient expression of patella position than those currently in use is described. Lateral radiographs of 114 normal knees were measured and the diagonal length of the patella was compared with the length of the ligamentum patellae. It was found that both measurements were approximately equal and that normal variation did not exceed 20%. The ratio of the patella to the patellar ligament may therefore be used as an index of patella height.

A new total knee rating system has been developed by The Knee Society to provide an up-to-date more stringent evaluation form. The system is subdivided into a knee score that rates only the knee joint itself and a functional score that rates the patient's ability to walk and climb stairs. The dual rating system eliminates the problem of declining knee scores associated with patient infirmity.

Girgis, Fakhry G. M.D., PhD.; Marshall, John L. D.V.M., M.D.; MONA JEM, A R S Al. M.D. Author Information

BACKGROUND: Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. OBJECTIVE: To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. METHODS: A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. RESULTS: The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). CONCLUSIONS: The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

PURPOSE OF REVIEW: This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage. RECENT FINDINGS: Studies during the past 2 years have uncovered novel pathways that, when activated, cause the normally quiescent articular chondrocytes to become activated and undergo a phenotypic shift, leading to the disruption of homeostasis and ultimately to the aberrant expression of proinflammatory and catabolic genes. Studies in animal models and retrieved human tissues indicate that proinflammatory factors may be produced by the chondrocytes themselves or by the synovium and other surrounding tissues, even in the absence of overt inflammation, and that multiple pathways converge on the upregulation of aggrecanases and collagenases, especially MMP-13. Particular attention has been paid to the contribution of synovitis in posttraumatic joint injury, such as meniscal tears, and the protective role of the pericellular matrix in mediating chondrocyte responses through receptors, such as discoidin domain receptor-2 and syndecan-4. New findings about intracellular signals, including the transcription factors NF-κB, C/EBPβ, ETS, Runx2, and hypoxia-inducible factor-2α, and their modulation by inflammatory cytokines, chemokines, adipokines, Toll-like receptor ligands, and receptor for advanced glycation end-products, as well as CpG methylation and microRNAs, are reviewed. SUMMARY: Further work on mediators and pathways that are common across different models and occur in human osteoarthritis and that impact the osteoarthritis disease process at different stages of initiation and progression will inform us about new directions for targeted therapies.

BACKGROUND: Although systemic lupus erythematosus is associated with premature myocardial infarction, the prevalence of underlying atherosclerosis and its relation to traditional risk factors for cardiovascular disease and lupus-related factors have not been examined in a case-control study. METHODS: In 197 patients with lupus and 197 matched controls, we performed carotid ultrasonography, echocardiography, and an assessment for risk factors for cardiovascular disease. The patients were also evaluated with respect to their clinical and serologic features, inflammatory mediators, and disease treatment. RESULTS: The risk factors for cardiovascular disease were similar among patients and controls. Atherosclerosis (carotid plaque) was more prevalent among patients than the controls (37.1 percent vs. 15.2 percent, P<0.001). In multivariate analysis, only older age, the presence of systemic lupus erythematosus (odds ratio, 4.8; 95 percent confidence interval, 2.6 to 8.7), and a higher serum cholesterol level were independently related to the presence of plaque. As compared with patients without plaque, patients with plaque were older, had a longer duration of disease and more disease-related damage, and were less likely to have multiple autoantibodies or to have been treated with prednisone, cyclophosphamide, or hydroxychloroquine. In multivariate analyses including patients with lupus, independent predictors of plaque were a longer duration of disease, a higher damage-index score, a lower incidence of the use of cyclophosphamide, and the absence of anti-Smith antibodies. CONCLUSIONS: Atherosclerosis occurs prematurely in patients with systemic lupus erythematosus and is independent of traditional risk factors for cardiovascular disease. The clinical profile of patients with lupus and atherosclerosis suggests a role for disease-related factors in atherogenesis and underscores the need for trials of more focused and effective antiinflammatory therapy.

BACKGROUND: Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis. METHODS: In this 1-year trial, we randomly assigned 251 patients, in a 2:1:1:1 ratio, to receive subcutaneous tocilizumab (at a dose of 162 mg) weekly or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. The primary outcome was the rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper. The key secondary outcome was the rate of remission in each tocilizumab group as compared with the placebo group that underwent the 52-week prednisone taper. Dosing of prednisone and safety were also assessed. RESULTS: Sustained remission at week 52 occurred in 56% of the patients treated with tocilizumab weekly and in 53% of those treated with tocilizumab every other week, as compared with 14% of those in the placebo group that underwent the 26-week prednisone taper and 18% of those in the placebo group that underwent the 52-week prednisone taper (P<0.001 for the comparisons of either active treatment with placebo). The cumulative median prednisone dose over the 52-week period was 1862 mg in each tocilizumab group, as compared with 3296 mg in the placebo group that underwent the 26-week taper (P<0.001 for both comparisons) and 3818 mg in the placebo group that underwent the 52-week taper (P<0.001 for both comparisons). Serious adverse events occurred in 15% of the patients in the group that received tocilizumab weekly, 14% of those in the group that received tocilizumab every other week, 22% of those in the placebo group that underwent the 26-week taper, and 25% of those in the placebo group that underwent the 52-week taper. Anterior ischemic optic neuropathy developed in one patient in the group that received tocilizumab every other week. CONCLUSIONS: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT01791153 .).

Platelet-rich plasma (PRP) has been utilized in surgery for 2 decades; there has been a recent interest in the use of PRP for the treatment of sports-related injuries. PRP contains growth factors and bioactive proteins that influence the healing of tendon, ligament, muscle, and bone. This article examines the basic science of PRP, and it describes the current clinical applications in sports medicine. This study reviews and evaluates the human studies that have been published in the orthopaedic surgery and sports medicine literature. The use of PRP in amateur and professional sports is reviewed, and the regulation of PRP by antidoping agencies is discussed.

OBJECTIVE: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.

The microvascular anatomy of the medial and lateral menisci of the human knee was investigated in 20 cadaver specimens by histology and tissue clearing (Spalteholz) techniques. It was found that the menisci are supplied by branches of the lateral, medial, and middle genicular arteries. A perimeniscal capillary plexus originating in the capsular and synovial tissues of the joint supplies the peripheral 10-25% of the menisci. A peripheral, vascular, synovial fringe extends a short distance over both the femoral and tibial surfaces of the menisci but does not contribute any vessels to the meniscal stroma. The posterolateral aspect of the lateral meniscus adjacent to the popliteal tendon is devoid of penetrating peripheral vessels as well as a synovial fringe. The anterior and posterior horn attachments of the menisci are covered with vascular synovial tissue and appear to have a good blood supply.

BACKGROUND: Surgery for spinal stenosis is widely performed, but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials. METHODS: Surgical candidates with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis (as confirmed on imaging) were enrolled in either a randomized cohort or an observational cohort at 13 U.S. spine clinics. Treatment was decompressive surgery or usual nonsurgical care. The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and the modified Oswestry Disability Index at 6 weeks, 3 months, 6 months, and 1 and 2 years. RESULTS: A total of 289 patients were enrolled in the randomized cohort, and 365 patients were enrolled in the observational cohort. At 2 years, 67% of patients who were randomly assigned to surgery had undergone surgery, whereas 43% of those who were randomly assigned to receive nonsurgical care had also undergone surgery. Despite the high level of nonadherence, the intention-to-treat analysis of the randomized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain, with a mean difference in change from baseline of 7.8 (95% confidence interval, 1.5 to 14.1); however, there was no significant difference in scores on physical function or on the Oswestry Disability Index. The as-treated analysis, which combined both cohorts and was adjusted for potential confounders, showed a significant advantage for surgery by 3 months for all primary outcomes; these changes remained significant at 2 years. CONCLUSIONS: In the combined as-treated analysis, patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically. (ClinicalTrials.gov number, NCT00000411 [ClinicalTrials.gov].).