Osteoarthritis (OA) ranks globally among the 50 most common sequelae of diseases and injuries, affecting over 250 million people or 4% of the world’s population [39]. Of the global disease burden for OA, knee OA constitutes 83% [39]. A detailed analysis of Medicare beneficiaries reported the TKA annual utilization rate ranging from 287,006 in 2006 to 301,956 in 2010 [26]. The demand for TKA is expected to grow exponentially over the coming decades with epidemiological data suggesting a 673% increase in the United States by 2030, representing 3.48 million procedures annually [22]. As a polymorphic disease with a variety of clinical presentations, OA is challenging to rigorously define. A commonly encountered definition of OA describes ‘‘...a heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone and at the joint margins’’ [1]. The pathogenesis of OA is poorly understood but is thought to include a complex interplay among mechanical, biochemical, cellular, genetic, and immunologic phenomena [7]. Several attempts to develop diagnostic criteria for OA were previously undertaken and incorporate patientreported joint pain in conjunction with consistent radiographic findings [1, 6, 24]. OA generally can be subcategorized into primary (idiopathic) and secondary OA [1, 25]. Common causes of secondary OA include posttraumatic, dysplastic, infectious, inflammatory, or biochemical etiologies that are relatively well understood. Although the etiology of primary OA remains largely undefined, genetic factors, age-related physiological changes, ethnicity, and biomechanical factors likely play an important role [16]. Plain radiography remains a mainstay in the diagnosis of OA. The first formalized attempts at establishing a radiographic classification scheme for OA were described by Kellgren and Lawrence (KL) in 1957 [19]. After studying rheumatism in coal miners at the Bedford Colliery in North West England [18], Kellgren investigated the interand intraobserver reliability of radiographic changes of rheumatism observed in the hand [17]. After concluding that there was wide disagreement among different observers, KL endeavored to establish a classification scheme with an associated set of standardized radiographs for OA of diarthrodial joints. They proposed a five-grade classification scheme and examined plain radiographs of eight joints including the distal interphalangeal joint (DIP), metacarpophalangeal joint (MCP), first carpometacarpal joint (CMC), wrist, cervical spine, lumbar spine, hips, and knees to calculate the interand intraobserver reliability of each [19]. They found that the tibiofemoral joint of the knee had the highest interobserver correlation coefficient of r = 0.83 (range of all joints studied, 0.10–0.83) as well as the second highest intraobserver correlation coefficient of Each author certifies that he or she, or a member of his or her immediate family, has no funding or commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research editors and board members are on file with the publication and can be viewed on request.

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Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis.

Systemic sclerosis is a chronic autoimmune disease of still not fully understood pathogenesis. Fibrosis, vascular wall damage, and disturbances of innate and acquired immune responses with autoantibody production are prominent features. Systemic sclerosis has specific subsets with different autoantibodies, and differences in the affected skin areas. The suspicion of systemic sclerosis and establishing the diagnosis will be facilitated by the criteria created by EULAR/ACR experts. The treatment of this autoimmune disease remains a challenge for clinicians and new therapeutic options are constantly sought. The occurrence of various symptoms and the involvement of many organs and systems make systemic sclerosis a multidisciplinary disease and require a holistic approach. The present article summarizes different clinical features of systemic sclerosis and the profile of autoantibodies and discusses recent rules and future perspectives in disease management.

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Systemic sclerosis - multidisciplinary disease: clinical features and treatment.

Systemic sclerosis is a multisystem autoimmune disorder that involves the gastrointestinal tract in more than 90% of patients. This involvement can extend from the mouth to the anus, with the oesophagus and anorectum most frequently affected. Gut complications result in a plethora of presentations that impair oral intake and faecal continence and, consequently, have an adverse effect on patient quality of life, resulting in referral to gastroenterologists. The cornerstones of gastrointestinal symptom management are to optimize symptom relief and monitor for complications, in particular anaemia and malabsorption. Early intervention in patients who develop these complications is critical to minimize disease progression and improve prognosis. In the future, enhanced therapeutic strategies should be developed, based on an ever-improving understanding of the intestinal pathophysiology of systemic sclerosis. This Review describes the most commonly occurring clinical scenarios of gastrointestinal involvement in patients with systemic sclerosis as they present to the gastroenterologist, with recommendations for the suggested assessment protocol and therapy in each situation.

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Current management of the gastrointestinal complications of systemic sclerosis.

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal. Newer agents targeting the pathogenic mechanisms underlying SSc-ILD, including fibrotic and inflammatory pathways, lymphocytes, cell-cell and cell-extracellular membrane interactions, hold promise for better treatment outcomes, including improved lung function, patient-related outcomes and quality of life. Here we review ongoing trials of established and novel agents that are currently recruiting patients with SSc-ILD.

/pdf/ongoing-clinical-trials-and-treatment-options-for-patients-tcsyuw4nbc.pdf

Ongoing clinical trials and treatment options for patients with systemic sclerosis–associated interstitial lung disease

Systemic sclerosis (SSc) is a chronic systemic disease characterized by microvasculopathy, autoantibodies, and extensive fibrosis. Intestinal involvement is frequent in SSc and represents a significant cause of morbidity. The pathogenesis of intestinal involvement includes vascular damage, nerve dysfunction, smooth muscle atrophy, and fibrosis, causing hypomotility, which leads to small intestinal bacterial overgrowth (SIBO), malabsorption, malnutrition, diarrhea, pseudo-obstruction, constipation, pneumatosis intestinalis, and fecal incontinence. Manifestations are often troublesome and reduce quality of life and life expectancy. Assessment of intestinal involvement includes screening for small intestine hypomotility, malnutrition, SIBO, and anorectal dysfunction. Current management of intestinal manifestations is largely inadequate. Patients with diarrhea are managed with low-fat diet, medium-chain triglycerides, avoidance of lactulose and fructose, and control of bacterial overgrowth with antibiotics for SIBO. In diarrhea/malabsorption, bile acid sequestrant and pancreatic enzyme supplementation may help, and nutritional support is needed. General measures are applied for constipation, and intestine rest plus antibiotics for pseudo-obstruction. Fecal incontinence is managed with measures for associated SIBO, or constipation, and with behavioral therapies. Pneumatosis intestinalis is usually an incidental finding that does not require any specific treatment. Immunomoduation should be considered early in intestinal involvement. Multidisciplinary approach of intestinal manifestations in SSc by gastroenterologists and rheumatologists is required for optimum management.

Intestinal Involvement in Systemic Sclerosis: A Clinical Review.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibroproliferative alterations of the microvasculature leading to fibrosis and loss of function of the skin and internal organs. Gastrointestinal manifestations of SSc are the most commonly encountered complications of the disease affecting nearly 90% of the SSc population. Among these complications, the esophagus and the anorectum are the most commonly affected. However, this devastating disorder does not spare any part of the gastrointestinal tract (GIT), and includes the oral cavity, esophagus, stomach, small and large bowels as well as the liver and pancreas. In this review, we present the current understanding of the pathophysiologic mechanisms of SSc including vasculopathy, endothelial to mesenchymal transformation as well as the autoimmune pathogenetic pathways. We also discuss the clinical presentation and diagnosis of each part of the GIT affected by SSc. Finally, we highlight the latest developments in the management of this disease, addressing the severe malnutrition that affects this vulnerable patient population and ways to assess and improve the nutritional status of the patients.

https://www.longdom.org/open-access/gastrointestinal-manifestations-of-systemic-sclerosis-2161-1149-1000235.pdf

Gastrointestinal Manifestations of Systemic Sclerosis

The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival, among patients with Sickle Cell Disease (SCD). This prolonged survival however introduces, a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics.

https://www.longdom.org/open-access/rheumatoid-arthritis-in-sicklecell-population-pathophysiologic-insightsclinical-evaluation-and-management-2161-1149-1000225.pdf

Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management.

Background/Purpose: Accumulating evidence indicates a relationship between Cardiovascular Disease (CVD) and osteoporosis. Hypertension, a known risk factor for CVD is also associated with low Bone Mineral Density (BMD). We hypothesize that Pulse Pressure (PP); a CVD risk factor is associated with BMD. Methods: Data from two consecutive cycles of National Health and Nutritional Examination Survey (NHANES) from 2009-2010 and 2011-2012. Point estimates of demographic variables were calculated using descriptive methods. Study participants were divided into 4 groups based on quartile distribution of PP. Multivariate linear regression analysis was performed to assess the relationship between BMD and PP. Results: A total of 8,179 NHANES participants were included in the study (Tables 1-3). The cohort’s mean age (± SE) was 53.3 years 0.19, mean BMI (± SE) 29.6 kg/m2 ± 0.07. PP was significantly higher with increased age, among Blacks (57.4 ± 0.52) and Hispanics (57.5 ± 0.19) compared to whites (53.9 ± 0.29), and for men (57.2 ± 0.16) when compared to women (54.1 ± 0.17), p<0.05. After adjusting for age, sex, race, menopause, body mass index, family history of osteoporosis, PP was associated with femoral neck BMD, β=-0.0005, p<0.05 but was not significantly associated with lumbar spine BMD, β=-0.0002, p=0.07. Conclusion: Our results support the hypothesis that wide PP is associated with low BMD. This negative association was demonstrated at the femoral neck where bone loss and osteoporotic fractures occur at a more advanced stage, further supporting the relationship between atherosclerosis and osteoporosis risk. These findings have the potential for identifying high osteoporotic risk patients among those with wide pulse pressure, providing further indications for bone mineral density testing among these elderly frail patients. Further research is needed to investigate the mechanisms behind the relationship between PP and BMD.

https://www.longdom.org/open-access/the-relationship-of-pulse-pressure-and-bone-mineral-density-in-adultusa-population-analysis-of-the-national-health-and-nutritional-2161-1149-1000240.pdf

The Relationship of Pulse Pressure and Bone Mineral Density in Adult USA Population: Analysis of the National Health and Nutritional Examination Survey.

Idiopathic inflammatory myopathies are rare autoimmune disorders characterized by proximal muscle weakness, elevation of muscle enzymes, abnormal electromyogram and imaging studies revealing areas of edema and inflammation. Initial approach to inflammatory myopathies includes steroids and immunosuppressive agents, with most individuals responding satisfactorily to therapy. However, treatment-refractory myopathies prompts clinicians to use second line agents to achieve remission. In this case series, we describe three patients with refractory idiopathic inflammatory myopathies who were treated with tacrolimus (TAC) added to mycophenolate mofetil (MMF) and steroid therapy, who achieved clinical and biochemical remission.

https://www.longdom.org/open-access/tacrolimusinduced-remission-in-drug-resistant-inflammatory-myopathy-a-case-series-2161-1149-1000238.pdf

Yair Saperstein

Papers

Gastrointestinal Manifestations of Systemic Sclerosis

Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management.

The Relationship of Pulse Pressure and Bone Mineral Density in Adult USA Population: Analysis of the National Health and Nutritional Examination Survey.

Tacrolimus-Induced Remission in Drug Resistant Inflammatory Myopathy: A Case Series.