Interstitial lung abnormalities in patients with early rheumatoid arthritis: A pilot study evaluating prevalence and progression.

OBJECTIVE:Pulmonary disease is a leading cause of morbidity and mortality in rheumatoid arthritis (RA). In this study, we investigated the prevalence and progression of interstitial lung abnormalities (ILA) in a prospective cohort study of 18 subjects with early RA. METHODS:Eighteen adults diagnosed with anti-citrullinated protein-antibody-positive RA within the prior year underwent baseline high-resolution computed tomography (HRCT), symptom assessment, and pulmonary function and laboratory testing. The follow-up HRCT and clinical assessment were completed after 1 year. RESULTS:Seven of the 18 patients (39%) had baseline HRCT abnormalities including septal thickening, honeycombing, ground glass opacities, and/or traction bronchiectasis. At follow-up, 6 out of the 7 subjects (86%) with ILAs at baseline exhibited progression, while 10 out of 11 (91%) without ILAs at baseline remained stable. A higher Clinical Chronic Obstructive Pulmonary Disease Questionnaire score was associated with both the presence and progression of HRCT abnormalities (10 vs 2, p=0.045; 10 vs 2, p=0.009, respectively). C-reactive protein (CRP) trended higher in patients with radiologic abnormalities (3.5 mg/L vs 1.1 mg/L, p=0.08) and was significantly higher in those with progression (3.5 mg/L vs 1 mg/L, p=0.024). Smoking, pulmonary function, and autoantibodies were not associated with HRCT abnormalities. CONCLUSION:ILAs are prevalent in patients with early RA. If identified at baseline, radiographic progression of ILAs after 1 year is likely, while those without ILAs at baseline are unlikely to develop new ILAs. In addition, early respiratory symptoms and higher CRP levels may correlate with the presence and progression of underlying ILAs

Heritability patterns in hand osteoarthritis: the role of osteophytes

Abstract Introduction The objective of the present study was to assess heritability of clinical and radiographic features of hand osteoarthritis (OA) in affected patients and their siblings. Methods A convenience sample of patients with clinical and radiographic hand OA and their siblings were evaluated by examination and radiography. Radiographs were scored for hand OA features by radiographic atlas. The heritability of hand OA phenotypes was assessed for clinical and radiographic measures based on anatomic locations and radiographic characteristics. Phenotypic data were transformed to reduce non-normality, if necessary. A variance components approach was used to calculate heritability. Results One hundred and thirty-six probands with hand OA and their sibling(s) were enrolled. By anatomic location, the highest heritability was seen with involvement of the first interphalangeal joint (h 2 = 0.63, P = 0.00004), the first carpometacarpal joint (h 2 = 0.38, P = 0.01), the distal interphalangeal joints (h 2 = 0.36, P = 0.02), and the proximal interphalangeal joints (h 2 = 0.30, P = 0.03) with osteophytes. The number and severity of joints with osteophyte involvement was heritable overall (h 2 = 0.38, P = 0.008 for number and h 2 = 0.35, P = 0.01 for severity) and for all interphalangeal joints (h 2 = 0.42, P = 0.004 and h 2 = 0.33, P = 0.02). The severity of carpometacarpal joint involvement was also heritable (h 2 = 0.53, P = 0.0006). Similar results were obtained when the analysis was limited to the Caucasian sample. Conclusions In a population with clinical and radiographic hand OA and their siblings, the presence of osteophytes was the most sensitive biomarker for hand OA heritability. Significant heritability was detected for anatomic phenotypes by joint location, severity of joint involvement with osteophytes as well as for overall number and degree of hand OA involvement. These findings are in agreement with the strong genetic predisposition for hand OA reported by others. The results support phenotyping based on severity of osteophytes and a joint-specific approach. More specific phenotypes may hold greater promise in the study of genetics in hand OA

Method for separating single-wall carbon nanotubes and compositions thereof

The invention relates to a process for sorting and separating a mixture of (n, m) type single-wall carbon nanotubes according to (n, m) type. A mixture of (n, m) type single-wall carbon nanotubes is suspended such that the single-wall carbon nanotubes are individually dispersed. The nanotube suspension can be done in a surfactant-water solution and the surfactant surrounding the nanotubes keeps the nanotube isolated and from aggregating with other nanotubes. The nanotube suspension is acidified to protonate a fraction of the nanotubes. An electric field is applied and the protonated nanotubes migrate in the electric fields at different rates dependent on their (n, m) type. Fractions of nanotubes are collected at different fractionation times. The process of protonation, applying an electric field, and fractionation is repeated at increasingly higher pH to separated the (n, m) nanotube mixture into individual (n, m) nanotube fractions. The separation enables new electronic devices requiring selected (n, m) nanotube types

The utility of MRI in predicting radiographic erosions in the metatarsophalangeal joints of the rheumatoid foot: a prospective longitudinal cohort study

INTRODUCTION: Magnetic resonance imaging (MRI) may reveal rheumatoid arthritis (RA) changes in the feet when hands are normal. The purpose of this study was to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a metatarsophalangeal (MTP) erosion on MRI to predict a subsequent radiographic erosion in the same joint. Similar analyses were performed for bone marrow edema, predicting a subsequent MRI erosion. Descriptive results of other lesions are reported. METHODS: Fifty patients with RA of less than 5 years' duration who were rheumatoid factor-positive and/or anti-cyclic citrullinated peptide-positive were recruited. Patients on anti-tumor necrosis factor (TNF) therapy were excluded. Anti-TNF therapy could begin after enrollment. MRI and radiographs of the 3rd, 4th, and 5th MTP joints bilaterally were taken at baseline and at 6, 12, and 24 months. Clinical data were collected. RESULTS: Fifty patients were recruited; 46 patients had suitable data. Results for MRI erosions predicting subsequent radiographic erosions for 6, 12, and 24 months, respectively, were as follows: sensitivity 0.75, 0.60, 0.75; specificity 0.93, 0.94, 0.94; PPV 0.086, 0.10, 0.17; NPV 0.998, 0.995, 0.995. Results for MRI bone marrow edema predicting MRI erosions at 6 and 12 months, respectively, revealed sensitivity 0.50, 0.67; specificity 0.97, 0.97; PPV 0.25, 0.50; NPV 0.99, 0.99. Synovitis was the most common finding and, when present in isolation, resolved on 67.3% of subsequent studies. MRI erosions persisted on subsequent studies with one exception. Forty-six percent of the cohort was on anti-TNF therapy after study inception. CONCLUSIONS: The PPV of MRI erosions to predict subsequent radiographic erosions was low. Similarly, the PPV of bone marrow edema to predict a later MRI erosion was low. Alternatively, the NPV of the absence of an MRI erosion or bone marrow edema predicts that a later radiographic erosion or MRI erosion will likely not develop. Anti-TNF therapies may have resulted in the lower-than-anticipated PPVs. MRI descriptions of bone edema may represent a more critical time to treat in order to avoid damage, whereas an MRI erosion represents more permanent damage. This study suggests that imaging modalities more sensitive than radiographs are necessary to monitor disease in the biologic era

Modulation of synaptic function by VAC14, a protein that regulates the phosphoinositides PI(3,5)P 2 and PI(5)P

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102191/1/embj2012200.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102191/2/embj2012200-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102191/3/embj2012200-reviewer_comments.pd

Effect of Tobacco Smoking on the Clinical, Histopathological, and Serological Manifestations of Sjögren’s Syndrome

Objectives To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca

Albumin Administration in Acute Ischemic Stroke: Safety Analysis of the ALIAS Part 2 Multicenter Trial

BACKGROUND: Albumin treatment of ischemic stroke was associated with cardiopulmonary adverse events in previous studies and a low incidence of intracranial hemorrhage. We sought to describe the neurological and cardiopulmonary adverse events in the ALIAS Part 2 Multicenter Trial. METHODS: Ischemic stroke patients, aged 18-83 and a baseline NIHSS ≥ 6, were randomized to treatment with ALB or saline control within 5 hours of stroke onset. Neurological adverse events included symptomatic intracranial hemorrhage, hemicraniectomy, neurological deterioration and neurological death. Cardiopulmonary adverse events included pulmonary edema/congestive heart failure, acute coronary syndromes, atrial fibrillation, pneumonia and pulmonary thromboembolism. RESULTS: Among 830 patients, neurological and cardiopulmonary adverse events were not differentially associated with poor outcome between ALB and saline control subjects. The rate of symptomatic intracranial hemorrhage in the first 24h was low overall (2.9%, 24/830) but more common in the ALB treated subjects (RR = 2.4, CI95 1.01-5.8). The rate of pulmonary edema/CHF in the first 48h was 7.9% (59/830) and was more common among ALB treated subjects (RR = 10.7, CI95 4.3-26.6); this complication was expected and was satisfactorily managed with mandated diuretic administration and intravenous fluid guidelines. Troponin elevations in the first 48h were common, occurring without ECG change or cardiac symptoms in 52 subjects (12.5%). CONCLUSIONS: ALB therapy was associated with an increase in symptomatic ICH and pulmonary edema/congestive heart failure but this did not affect final outcomes. Troponin elevation occurs routinely in the first 48 hours after acute ischemic stroke. TRIAL REGISTRATION: ClincalTrials.gov NCT00235495

Examining Treatment Decision-Making Among Patients With Axial Spondyloarthritis: Insights From a Conjoint Analysis Survey

OBJECTIVE: The number of therapies for axial spondyloarthritis (axSpA) is increasing. Thus, it has become more challenging for patients and physicians to navigate the risk-benefit profiles of the various treatment options. In this study, we used conjoint analysis-a form of trade-off analysis that elucidates how people make complex decisions by balancing competing factors-to examine patient decision-making surrounding medication options for axSpA. METHODS: We conducted an adaptive choice-based conjoint analysis survey for patients with axSpA to assess the relative importance of medication attributes (eg, chance of symptom improvement, risk of side effects, route of administration, etc) in their decision-making. We also performed logistic regression to explore whether patient demographics and disease characteristics predicted decision-making. RESULTS: Overall, 397 patients with axSpA completed the conjoint analysis survey. Patients prioritized medication efficacy (importance score 26.8%), cost (26.3%), and route of administration (13.9%) as most important in their decision-making. These were followed by risk of lymphoma (9.5%), dosing frequency (7.2%), risk of serious infection (6.0%), tolerability of side effects (5.3%), and clinic visit and laboratory test frequency (4.8%). In regression analyses, there were few significant associations between patients\u27 treatment preferences and sociodemographic and axSpA characteristics. CONCLUSIONS: Treatment decision-making in axSpA is highly individualized, and demographics and baseline disease characteristics are poor predictors of individual preferences. This calls for the development of online shared decision-making tools for patients and providers, with the goal of selecting a treatment that is consistent with patients\u27 preferences