Present and Future CP Measurements

We review theoretical and experimental results on CP violation summarizing the discussions in the working group on CP violation at the UK phenomenology workshop 2000 in Durham.Comment: 104 pages, Latex, to appear in Journal of Physics

Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant

Anti-melanoma differentiation-associated protein 5 (anti-MDA5) is a subset of dermatomyositis associated with respiratory complications, in which rapidly progressive interstitial lung disease (RPILD) is commonly cited, and spontaneous pneumomediastinum (SPM) is a rare complication. In medical literature, aggressive immunosuppressive therapy has been the mainstay of anti-MDA5-associated SPM management. Here, we report the first MDA5 case with SPM which was successfully treated with a double-lung transplant. We present a 48-year-old male who presented with multiple constitutional symptoms such as fevers, weight loss, malaise, and arthralgias, in association with erythroderma over the ears and fingers. Imaging of the chest demonstrated peripheral airspace disease, and myositis-specific serology returned positive for anti-Jo1 (medium-positive), anti-Ro52 (high-positive), and anti-MDA5 (weak-positive) autoantibodies. Therefore, the patient was begun on immunosuppressive therapy as the leading diagnosis included autoimmune myositis, possibly antisynthetase syndrome with interstitial lung disease (ILD). A year later, the patient presented with progressive shortness of breath, widespread macular erythematous facial rash, and new erythematous ulcerations over the fingertips. Imaging demonstrated a new SPM at this juncture. As the patient’s respiratory status continued to decline despite the use of immunosuppressive agents, a double-lung transplant was performed. Therefore, we propose that lung transplantation should be considered early in MDA5-SPM.</jats:p

Spontaneous Pneumomediastinum due to Anti-Melanoma Differentiation-Associated Protein 5 Requiring a Bilateral Lung Transplant

Anti-melanoma differentiation-associated protein 5 (anti-MDA5) is a subset of dermatomyositis associated with respiratory complications, in which rapidly progressive interstitial lung disease (RPILD) is commonly cited, and spontaneous pneumomediastinum (SPM) is a rare complication. In medical literature, aggressive immunosuppressive therapy has been the mainstay of anti-MDA5-associated SPM management. Here, we report the first MDA5 case with SPM which was successfully treated with a double-lung transplant. We present a 48-year-old male who presented with multiple constitutional symptoms such as fevers, weight loss, malaise, and arthralgias, in association with erythroderma over the ears and fingers. Imaging of the chest demonstrated peripheral airspace disease, and myositis-specific serology returned positive for anti-Jo1 (medium-positive), anti-Ro52 (high-positive), and anti-MDA5 (weak-positive) autoantibodies. Therefore, the patient was begun on immunosuppressive therapy as the leading diagnosis included autoimmune myositis, possibly antisynthetase syndrome with interstitial lung disease (ILD). A year later, the patient presented with progressive shortness of breath, widespread macular erythematous facial rash, and new erythematous ulcerations over the fingertips. Imaging demonstrated a new SPM at this juncture. As the patient’s respiratory status continued to decline despite the use of immunosuppressive agents, a double-lung transplant was performed. Therefore, we propose that lung transplantation should be considered early in MDA5-SPM

Epidemiology and Treatment of Peripheral Neuropathy in Systemic Sclerosis

ObjectiveThe epidemiology and treatment of peripheral neuropathy in systemic sclerosis (SSc) is poorly understood. The objectives of this study were to evaluate the incidence, prevalence, risk factors, and treatments of peripheral neuropathy in SSc.MethodsA systematic review of MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for literature reporting peripheral neuropathy in SSc was performed. Studies evaluating incidence, prevalence, risk factors, and treatments were synthesized. A metaanalysis using a random effects model was used to evaluate the prevalence of peripheral neuropathy.ResultsThis systematic review identified 113 studies that reported 949 of 2143 subjects with at least 1 type of peripheral neuropathy. The mean age was 48.5 years. The mean time between SSc onset and detection of peripheral neuropathy was 8.85 years. The pooled prevalence of neuropathy was 27.37% (95% CI 22.35–32.70). Risk factors for peripheral neuropathy in SSc included advanced diffuse disease, anticentromere antibodies, calcinosis cutis, ischemia of the vasa nervorum, iron deficiency anemia, metoclopramide, pembrolizumab, silicosis, and uremia. There were 73 subjects with successful treatments (n = 36 restoring sensation, n = 37 restoring motor or sensorimotor function). Treatments included decompression surgery, prednisone, cyclophosphamide, carbamazepine, transcutaneous electrical nerve stimulation, tricyclic antidepressants, and intravenous Ig.ConclusionAll-cause peripheral neuropathy is not uncommon in SSc. Compression neuropathies can be treated with decompression surgery. Observational data reporting immunosuppressives and anticonvulsants to treat peripheral neuropathy in SSc are limited and conflicting. Randomized controlled trials are needed to evaluate the efficacy of these interventions.</jats:sec

Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results

Background: Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods: Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016–July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results: We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives. In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives. Individual autoantibody specificities were > 98.2 and > 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7–189.2, p < 0.001) and strong positive (versus weak positive) results (4.4, 2.3–8.3, p < 0.001). Conclusions: We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies.Medicine, Faculty ofNon UBCMedicine, Department ofRheumatology, Division ofReviewedFacult

Line blot immunoassays in idiopathic inflammatory myopathies: retrospective review of diagnostic accuracy and factors predicting true positive results

Abstract Background Line blot immunoassays (LIA) for myositis-specific (MSA) and myositis-associated (MAA) autoantibodies have become commercially available. In the largest study of this kind, we evaluated the clinical performance of a widely used LIA for MSAs and MAAs. Methods Adults tested for MSA/MAA by LIA at a tertiary myositis centre (January 2016–July 2018) were identified. According to expert-defined diagnoses, true and false positive rates were calculated for strongly and weakly positive autoantibody results within three cohorts: idiopathic inflammatory myopathy (IIM), connective tissue disease (CTD) without myositis, and non-CTD/IIM. Factors associated with true positivity were determined. Results We analysed 342 cases. 67 (19.6%) had IIM, in whom 71 autoantibodies were detected (50 strong positives [70.4%], 21 weak positives [29.6%]). Of the strong positives, 48/50 (96.0%; 19 MSAs, 29 MAAs) were deemed true positives. Of the weak positives, 15/21 (71.4%; 3 MSAs, 12 MAAs) were deemed true positives. In CTD without myositis cases (n = 120), 31/61 (51.0%; 5 MSAs, 26 MAAs) autoantibodies were strongly positive, with 24/31 (77.4%; 0 MSAs, 24 MAAs) true positives. 30/61 (49.2%; 13 MSAs, 17 MAAs) were weakly positive, with 16/30 (53.3%; 0 MSAs, 16 MAAs) true positives. In non-CTD/IIM cases (n = 155), all 24 MSAs and 22 MAAs were false positives; these results included 17 (37.0%; 7 MSAs, 10 MAAs) strong positives. Individual autoantibody specificities were &gt; 98.2 and &gt; 97.5% for weakly and strongly positive results, respectively. True positivity was associated with high pre-test for IIM (odds ratio 50.8, 95% CI 13.7–189.2, p &lt; 0.001) and strong positive (versus weak positive) results (4.4, 2.3–8.3, p &lt; 0.001). Conclusions We demonstrated the high specificity of a myositis LIA in a clinical setting. However, a significant burden of false positive results was evident in those with a low pre-test likelihood of IIM and for weakly positive autoantibodies. </jats:sec