Association of Baseline Frailty with Patient-Reported Outcomes in Systemic Lupus Erythematosus at 1 Year.

The relationship of baseline frailty with subsequent patient-reported outcomes in systemic lupus erythematosus (SLE) remains unclear. We assessed these associations in a pilot prospective cohort study. Frailty based on the FRAIL scale and the Fried phenotype and patient-reported outcomes, namely Patient Reported Outcomes Measurement Information System computerized adaptive tests and Valued Life Activities disability, were measured at baseline and 1 year among women aged 18-70 years with SLE enrolled at a single center. Differences in Patient Reported Outcomes Measurement Information System computerized adaptive tests between frail and non-frail participants were evaluated using Wilcoxon rank sum tests, and the association of baseline frailty with self-report disability at 1 year was estimated using linear regression. Of 51 participants, 24% (FRAIL scale) and 16% (Fried phenotype) met criteria for frailty at baseline despite median age of 55.0 and 56.0 years, respectively. Women with (versus without) baseline frailty using either measure had worse 1-year Patient Reported Outcomes Measurement Information System computerized adaptive test scores across multiple domains and greater self-report disability. Baseline frailty was significantly associated with self-report disability at 1 year (FRAIL scale: parameter estimate 0.55, 95% confidence interval (CI) 0.21-0.89, p<0.01; Fried phenotype: parameter estimate 0.61, 95% CI 0.22-1.00, p<0.01), including only slight attenuation after adjustment for SLE cumulative organ damage (FRAIL scale: parameter estimate 0.45, 95% CI 0.09-0.81, p=0.02; Fried phenotype: parameter estimate 0.49, 95% CI 0.09-0.90, p=0.02). These preliminary findings support frailty as an independent risk factor for clinically relevant patient-reported outcomes, including disability onset, among women with SLE.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis

To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.

OBJECTIVE: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. METHODS: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. RESULTS: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. CONCLUSION: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

Osteoarthritis year in review 2018: clinical.

Osteoarthritis (OA) is the most common joint disease in the world, with an age-associated increase in both incidence and prevalence. Clinical and epidemiologic research is crucial to better understand risk factors for disease, find the best treatments for symptoms, and identify therapies to slow down or even prevent disease progression. This paper is based on a systematic review of the osteoarthritis literature published in English between 2017/05/01 and 2018/04/25, with a focus on papers which have the potential to improve patient care, or which suggest novel areas for future research.

Feasibility of Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests in systemic lupus erythematosus outpatients.

Objective The aims of this study were to assess the feasibility of administering Patient-Reported Outcomes Measurement Information System (PROMIS®) computerized adaptive tests (CATs) to outpatients with systemic lupus erythematosus (SLE). Methods Adults with SLE were recruited during routine outpatient visits at an SLE Center of Excellence. Participants completed 14 PROMIS CATs and provided feedback on their experience. Differences in socio-demographic and clinical characteristics between participants and non-participants were evaluated. Results A total of 204 (86%) of 238 socioeconomically and racially diverse SLE patients completed PROMIS CATs. There were no significant differences between participants and non-participants. Time constraints were cited most frequently as reasons for non-participation. More than 75% of individuals submitted positive comments, including approval of the content and format of questions, and the survey's promotion of self-reflection. A minority of participants cited challenges, most often related to question phrasing (8%) and technical difficulties (6%). Conclusions The administration of PROMIS CATs was feasible and positively received in a diverse cohort of SLE outpatients. Neither socio-demographic nor disease characteristics were significant barriers to successful completion of PROMIS CATs. PROMIS CATs have great potential for efficiently measuring important patient-centered outcomes in routine clinical care of a wide range of SLE patients.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future.

Systemic lupus erythematosus is not a risk factor for poor outcomes after total hip and total knee arthroplasty.

OBJECTIVES: Historically, arthroplasty in systemic lupus erythematosus (SLE) patients has been less successful than for patients with osteoarthritis (OA). It is not known if SLE remains an independent risk factor for poor arthroplasty outcomes or if other factors, such as avascular necrosis (AVN), continue to play a role. METHODS: A case-control study using data from a single-institution arthroplasty registry compared SLE total hip arthroplasty (THA) and total knee arthroplasty (TKA) with OA controls matched by age, gender and presence of AVN. Baseline, two-year administrative and self-report data, and diagnosis leading to arthroplasty were evaluated. RESULTS: A total of 54 primary SLE THA and 45 primary SLE TKA were identified from May 2007 through June 2011. AVN was present in 32% of SLE THA and no TKA. SLE THA had worse preoperative WOMAC pain (42.5 vs. 52.7; p = 0.01) and function (38.8 vs. 48.0; p = 0.05) compared with OA. However, at two years there was no difference in WOMAC pain (91.1 vs. 92.1; p = 0.77) or WOMAC function (86.4 vs. 90.8; p = 0.28). SLE TKA were similar to OA in both preoperative pain (42.6 vs. 48.4; p = 0.14) and function (42.1 vs. 46.8; p = 0.30) and two-year pain (85.7 vs. 88.6; p = 0.50) and function (83.7 vs. 85.1; p = 0.23). Compared to OA, SLE THA and TKA patients had more renal failure (14% vs. 1%; p = 0.007) and hypertension (52% vs. 29%; p = 0.009). In a multivariate linear regression, SLE was not predictive of either poor pain or poor function. CONCLUSIONS: While SLE patients have more comorbidities than OA, and SLE THA have worse preoperative pain and function compared with OA controls, SLE was not an independent risk factor for poor short-term pain or function after either hip or knee arthroplasty.

Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease.

OBJECTIVE: Much of what is known about the inflammatory response in the synovial membrane (SM) of patients with osteoarthritis (OA) comes from studies of synovial tissues from end-stage disease. In this study, we sought to better characterize the inflammatory infiltrate in symptomatic patients with early signs of knee OA, and to determine how inflammatory cell populations relate to the pattern of cytokine and degradative enzyme production. METHODS: Study populations comprised patients with degenerative meniscal tears and early cartilage thinning undergoing arthroscopic procedures (early OA) and patients undergoing total knee replacement for end-stage OA. Quantitative real-time polymerase chain reaction (PCR) was used to measure expression of SM cytokines and enzymes implicated in the pathogenesis of inflammatory arthritis and OA, as well as cell lineage-specific markers. We quantified synovial fluid (SF) cytokines and enzymes by enzyme-linked immunosorbent assay (ELISA) and SM cell populations by immunohistochemistry. RESULTS: We found increased levels of SF interleukin-15 (IL-15) protein in the early knee OA patients when compared to end-stage OA. Both SF IL-15 protein and numbers of CD8 cells within SM correlated with matrix metalloproteinase-1 (MMP-1) and three levels. TNF-alpha, IL-6 and IL-21 were also detectable in the SF of the majority of patients, and IL-15 levels were associated with IL-6 levels. CONCLUSION: IL-15 is elevated in early knee OA, suggesting activation of an innate immune response in the SM. The association of IL-15 expression with CD8 transcripts and MMPs implicates this cytokine in OA pathogenesis and as a candidate therapeutic target.

Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study.

OBJECTIVES: The "fetal origins of adult disease" hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual's future risk of rheumatoid arthritis (RA). METHODS: The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses' Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18. RESULTS: In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2-3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6). CONCLUSIONS: In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.

Anti-heparin platelet factor 4 antibodies in systemic lupus erythematosus are associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome.

OBJECTIVE: To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythematosus (SLE) patients with and without antiphospholipid antibodies (aPL). METHODS: Sera and clinical data were obtained from the Hospital for Special Surgery Autoimmune Disease Registry for 78 aPL-positive and 91 aPL-negative SLE patients without heparin-induced thrombocytopenia (HIT). Controls were 90 blood donors of comparable age and sex. Sera were assayed for anti-HPF4, IgG/IgM antiphospholipid antibodies (APhL), and IgG/IgM anti-beta2-glycoprotein 1 antibodies (anti-beta 2GP1). Serotonin release assays (SRAs) were performed for subjects with positive anti-HPF4. RESULTS: Positive anti-HPF4 was seen in 9% of aPL-positive SLE patients, 4% of aPL-negative SLE patients and 1% of controls (p = 0.026, aPL-positive SLE vs controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-beta2GP1, and inversely with complement C4. In immunoabsorption experiments, there was partial cross-reactivity of IgM anti-HPF4 with IgM APhL, but not with IgM anti-beta 2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; odds ratio (OR) 4.5, p = 0.019), and APS with arterial thrombosis (OR 6.1, p = 0.007). In multivariate linear regression analyses, APS and IgM APhL were independently associated with anti-HPF4. CONCLUSIONS: Anti-HPF4 is detectable in SLE patients with and without aPL in the absence of HIT, and is most prevalent in aPL-positive SLE patients. In this SLE cohort, anti-HPF4 correlates with IgM APhL, IgM anti-beta 2GP1 and inversely with C4, and is associated with manifestations of APS.

Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis.

OBJECTIVE: C-reactive protein (CRP) has been associated with disease progression in patients with osteoarthritis (OA), but the reasons for this remain unclear. We hypothesized that higher CRP would be related to local inflammatory findings in the joints of patients with OA. METHODS: Plasma and synovial membrane specimens from 54 OA patients undergoing total hip or knee arthroplasty or arthroscopy were obtained. Synovial fluid was obtained from 25 of these patients. Hematoxylin and eosin stained synovial membrane sections were scored for degree of inflammatory cell infiltration. Plasma high-sensitivity CRP (hsCRP) levels, and serum and synovial fluid interleukin (IL)-6 and IL-1beta levels were measured by enzyme-linked immunosorbent assay. RESULTS: Fifty-seven percent of patients with idiopathic OA had inflammatory infiltrates within the synovial membrane. The mean hsCRP level in patients with inflammatory infiltrates was significantly higher than those without inflammation (4.7 +/- 5.0 mg/L vs 1.7 +/- 3.6 mg/L, P = 0.003). There were significant correlations between hsCRP levels and synovial fluid IL-6 (r = 0.64, P = 0.0006), degree of synovial inflammatory infiltration (r = 0.43, P = 0.002), and body mass index (r = 0.31, P = 0.02). Multivariate analysis indicated that only degree of inflammatory infiltrate was significantly associated with hsCRP level (P = 0.026). CONCLUSION: These results suggest that systemic hsCRP levels reflect synovial inflammation in OA patients, perhaps by means of synovial IL-6 production. Future studies are needed to clarify how these infiltrates and their products may contribute to disease pathogenesis.

[Papillary fibroelastoma of the aortic valve coincident with a cystic tumor of the atrioventricular node]. / Papilläres Fibroelastom der Aortenklappe koinzident mit zystischem Tumor des Atrioventrikularknotens.

We describe a rare case of a papillary fibroelastoma of the aortic valve occurring simultaneously with a cystic tumor (a so-called mesothelioma) of the atrioventricular nodal region. At autopsy the tumor was found to prolapse into and occlude the right coronary ostium, leading to an acute, recurring myocardial infarction. Histological examination of the grossly unremarkable conduction system of the heart revealed a cystic tumor in the region of the atrioventricular node. To our knowledge, this is the first report of co-existence of these two rare cardiac tumors.

Amyloid myopathy masquerading as polymyositis.

OBJECTIVE: It is not well appreciated that the clinical presentation of amyloid myopathy can mimic that of polymyositis. By retrospective clinicopathologic analysis we determined distinctive features of amyloid myopathy that differentiate the 2 diseases. METHODS: Two patients with clinical and histologic evidence of an inflammatory myopathy had fatal outcomes despite appropriate treatment for polymyositis. Their clinical course and original pathologic specimens were reviewed. In addition, original tissue samples were obtained and analyzed using Congo red staining and immunoperoxidase. RESULTS: The initial diagnosis of polymyositis was supported in both cases by muscle biopsies showing inflammatory infiltrates and elevations of creatine phosphokinase and by classic electromyography. Retrospective evaluation of the initial muscle biopsies disclosed subtle but incontrovertible evidence of vascular amyloid. Further analysis of the original specimens confirmed the presence of immunoglobin light chain (AL) amyloid. CONCLUSION: Amyloid myopathy can mimic polymyositis. Both can have similar clinical symptoms, as well as inflammatory infiltrates on muscle biopsy. Failure to recognize amyloid myopathy deprives patients of potentially life prolonging treatment. Congo red staining and immunohistochemical analysis of tissue could prevent misdiagnosis.

Idiopathic thrombocytopenic purpura in a liver transplant recipient with previous primary biliary cirrhosis.

The loss of immunotolerance has been implicated in the pathogenesis of both primary biliary cirrhosis (PBC) and idiopathic, immune-mediated thrombocytopenic purpura (ITP). An association between these two autoimmune diseases has been well described. We describe a 41-year-old woman in whom ITP developed 457 days after liver transplantation for PBC while receiving immunosuppressive medications sufficient to maintain allograft function. Our case report, the first to describe post-transplant ITP in association with PBC, demonstrates the persistence of the underlying immune dysregulation of PBC after transplantation. The practice of decreasing the dosage of immunosuppressive medication to maintenance levels after transplantation may unmask the effects of this defect in immunotolerance.

[The juxta-oral organ (Chievitz organ)--a sensory organ in the bucco-temporal area?]. / Das juxtaorale Organ (Chievitz-Organ)--ein sensibles Organ in der Buccotemporalregion?

Samples of a juxtaoral organ were examined immunohistochemically with antibodies against light-chain cytokeratin (KL-1), cytokeratin 19, desmin, chromogranin, neuron-specific enolase, and S-100 protein. The epithelial cells were found to be immunoreactive only with the two cytokeratin antibodies. Transmission electron microscopy was also performed. The results are best compatible with a mechanoreceptor function of the organ.

[Trans-sphenoid gunshot injury of the head. Anatomic viewpoints]. / Die transsphenoidale Kopfschussverletzung. Anatomische Gesichtspunkte.

The transsphenoidal gunshot injury of the head is a subgroup of the temporal gunshot injury, generally with a bad prognosis quoad vitam. Important neural and vascular structures could be damaged by penetration of the missile. In our case the important structures were "missed" exactly and the patient survived without severe neurological deficits. With this case anatomical considerations of the transsphenoidal gunshot injury are made.

Primary cilia in normal human neocortical neurons.

Human neocortical neurons from the frontotemporal region were examined by serial ultrathin sectioning with the intention to establish the morphology and frequency of primary cilia (with a 9 + 0 tubular structure) in these cells. Each cell examined thoroughly showed one single cilium with a characteristic position and structure. The constant presence of these organelles may be a hint at an important function.