Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Correlates of family involvement before and during medical visits among older adults with high-risk diabetes.

AIMS: To examine the characteristics of patients with diabetes who regularly receive help from a supporter in preparing for and attending medical visits, and the association between this help and clinical risk factors for diabetes complications. METHODS: We linked survey data about family involvement for patients in the Veterans Health Administration system with poorly controlled Type 2 diabetes (n = 588; mean 67 years; 97% male) with health record data on blood pressure, glycaemic control and prescription-fill gaps. We used multivariable regression to assess whether supporter presence and, among patients with supporters, supporter role (visit preparation, accompaniment to medical visit or no involvement) were associated with concurrent trends in clinical risk factors over 2 years, adjusting for sociodemographic and health characteristics. RESULTS: Most patients (78%) had a main health supporter; of these, more had regular support for preparing for appointments (69%) than were regularly accompanied to them (45%). Patients with preparation help only were younger and more educated than accompanied patients. Support presence and type was not significantly associated with clinical risk factors. CONCLUSIONS: Family help preparing for appointments was common among these patients with high-risk diabetes. In its current form, family support for medical visits may not affect clinical factors in the short term. Supporters helping patients engage in medical visits may need training and assistance to have an impact on the clinical trajectory of patients with diabetes.

Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels.

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

Colchicine: a simple and effective treatment for pericarditis in systemic lupus erythematosus? A report of 10 cases.

OBJECTIVES: Pericardial involvement is a frequent manifestation of systemic lupus erythematosus (SLE). Growing evidence suggests that colchicine may be useful for acute or recurrent pericarditis. We report for the first time a series of 10 consecutive cases of SLE with pericarditis treated with colchicine. METHODS: Inclusion criteria in this retrospective study were diagnosis of SLE, pericarditis and receiving colchicine. RESULTS: We included 10 consecutive cases of SLE with pericarditis treated with colchicine (nine women, mean age at the index pericarditis 35 ± 12 years). Pericarditis was the initial manifestation of SLE for two patients, whereas eight patients had SLE lasting for a median of 2.5 years (15 days to 13 years) and had received prednisone (n = 7, 2-30 mg/d), hydroxychloroquine (n = 7), azathioprine (n = 3), methotrexate (n = 2), and mycophenolate mofetil (n = 1). For six patients, pericarditis was associated with other SLE manifestations. Altogether, colchicine avoided the use (n = 2) or increase in dosage (n = 5) of steroids in seven cases; the increase in steroids dosage was minimal for two patients. Colchicine 1 mg was given for a median of 39 days (10 days to 54 months). Symptoms completely resolved after a median of 2.5 days (1-30 days) after initiation of colchicine. Colchicine was maintained or resumed in six patients to prevent recurrence, with no further relapse. CONCLUSIONS: Colchicine may be safe and effective in treating SLE pericarditis and used as a steroids-sparing agent. These preliminary results need to be confirmed in a larger study with longer follow-up.

[NLRP3 inflammasome and visceral adipose tissue]. / Inflammasome NLRP3 et graisse viscérale.

It is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 diabetes are associated with an abnormal production of pro-inflammatory cytokines, an increased level of acute-phase proteins and an activation of inflammatory signalling pathways. These pro-inflammatory cytokines, mainly produced by adipose tissue macrophages, are involved in development of obesity-associated insulin resistance and in the progression from obesity to type 2 diabetes. Particularly, the interleukin-1 beta may play a key role through the activation of the NLRP3 inflammasome. Adipose tissue topography, more than the total amount of fat, may play an important pathogenic role. Indeed, the presence of metabolic abnormalities in obesity is associated with a deleterious immunological and inflammatory profile of visceral adipose tissue and with an increased activation of the NLRP3 inflammasome in macrophages infiltrating visceral adipose tissue. Targeting inflammation, especially NLRP3 inflammasome, may offer potential novel therapeutic perspectives in the prevention and treatment of type 2 diabetes.

Generalized anxiety disorder screening scores are associated with greater treatment need among Veterans with depression.

Comorbid anxiety and depression predict a poorer prognosis than either disorder occurring alone. It is unclear whether self-reported anxiety symptom scores identify patients with depression in need of more intensive mental health services. This study evaluated how anxiety symptoms predicted treatment receipt and outcomes among patients with new depression diagnoses in the Veterans Health Administration (VHA). Electronic medical record data from 128,917 VHA patients (71.6% assessed for anxiety, n = 92,237) with new diagnoses of depression were analyzed to examine how Generalized Anxiety Disorder-7 (GAD-7) scores predicted psychotropic medication prescriptions, psychotherapy receipt, acute care service utilization, and follow-up depression symptoms. Patients who reported severe symptoms of anxiety were significantly more likely to receive adequate acute phase and continuation phase antidepressant treatment, daytime anxiolytics/sedatives, nighttime sedative/hypnotics, and endorse more severe depression symptoms and suicidal ideation at follow-up. Patients who reported severe symptoms of anxiety at baseline were less likely to initiate psychotherapy. The GAD-7 may help identify depressed patients who have more severe disease burden and require additional mental health services.

Ruthenium oligonucleotides, targeting HPV16 E6 oncogene, inhibit the growth of cervical cancer cells under illumination by a mechanism involving p53.

High-risk Human Papillomaviruses (HPV) has been found to be associated with carcinomas of the cervix, penis, vulva/vagina, anus, mouth and oro-pharynx. As the main tumorigenic effects of the HPV have been attributed to the expression of E6 and E7 genes, different gene therapy approaches have been directed to block their expression such as antisense oligonucleotides (ASO), ribozymes and small interfering RNAs. In order to develop a gene-specific therapy for HPV-related cancers, we investigated a potential therapeutic strategy of gene silencing activated under illumination. Our aim according to this antisense therapy consisted in regulating the HPV16 E6 oncogene by using an E6-ASO derivatized with a polyazaaromatic ruthenium (Ru(II)) complex (E6-Ru-ASO) able, under visible illumination, to crosslink irreversibly the targeted sequence. We examined the effects of E6-Ru-ASO on the expression of E6 and on the cell growth of cervical cancer cells. We demonstrated using HPV16(+) SiHa cervical cancer cells that E6-Ru-ASO induces after illumination, a reactivation of p53, the most important target of E6, as well as the inhibition of cell proliferation with a selective repression of E6 at the protein level. These results suggest that E6-Ru ASOs, activated under illumination and specifically targeting E6, are capable of inhibiting HPV16(+) cervical cancer cell proliferation.

Longitudinal association between medication adherence and glycaemic control in Type 2 diabetes.

AIM: Despite the widespread assumption that adherence drives glycaemic control, there is little published support for this in Type 2 diabetes. The study objective was to determine whether self-reported medication adherence predicts future glycaemic control in Type 2 diabetes, after accounting for baseline control. METHODS: Medication adherence (4-item Morisky scale), glycaemic control (HbA(1c)%), and other variables were assessed in 287 adult primary care patients prescribed oral medication (40% also on insulin) for Type 2 diabetes. Glycaemic control was reassessed 6 months later. Regression analyses examined concurrent and future glycaemic control as a function of baseline medication adherence after adjustment for baseline glycaemia and other potential confounders. RESULTS: Only half of patients reported high adherence. Cross-sectional adjusted analysis replicated prior reports of an adherence-HbA(1c) association (P = 0.011). Even after adjusting for baseline HbA(1c), each one-point increase in baseline Morisky total score was associated with a 1.8 mmol/mol (or 0.16%) increase in HbA(1c) measured 6 months later. Additionally, baseline endorsement of forgetting to take medication was associated with a 4.7 mmol/mol (or 0.43%) increase in 6-month HbA(1c) (P = 0.005). This effect persisted after adjusting for psychological distress and did not vary by key demographic and medical features. CONCLUSIONS: Even after stringent adjustment for baseline glycaemic control, self-reported adherence to diabetes medication predicts long-term glycaemic control. The Morisky scale is an easy-to-use clinical tool to identify patients whose glycaemic control will subsequently worsen, regardless of age, gender and psychological distress.

Immunosuppressants reduce venous thrombosis relapse in Behçet's disease.

OBJECTIVE: To investigate and describe the long-term outcome of venous thrombosis in patients with Behçet's disease (BD). METHODS: In a retrospective cohort of 807 BD patients, a reported 296 patients (36.7%) (73.3% male, median age 30 years [interquartile range 24-36 years]) met the international classification criteria for BD and had venous thrombosis. We assessed factors associated with thrombosis relapse and mortality. RESULTS: There were a total of 586 venous thrombosis events, including 560 cases of deep thrombosis and 26 cases of superficial thrombosis. Deep venous thrombosis events included 323 cases of limb thrombosis (55.1%), 77 cases of cerebral venous thrombosis (13.1%), 57 cases of pulmonary embolism (9.7%), 63 cases of vena cava lesions (10.7%), 14 cases of Budd-Chiari syndrome (2.4%), and 13 cases of cervical vein thrombosis (2.2%). One hundred of 296 patients (33.8%) experienced at least 1 venous thrombosis relapse. The mortality rate was 6.4% (19 of 296 patients) after a median followup of 4.75 years (interquartile range 2-7 years). In univariate analysis, death was associated with cardiac involvement (P = 0.026) and Budd-Chiari syndrome (P = 0.004). In multivariate analysis, the use of immunosuppressive agents was found to prevent relapse of venous thrombosis (hazard ratio 0.27 [95% confidence interval 0.14-0.52], P = 0.00021), and there was a trend toward prevention of relapse with the use of glucocorticoids (hazard ratio 0.62 [95% confidence interval 0.40-0.97], P = 0.058). CONCLUSION: Immunosuppressive agents significantly reduce venous thrombosis relapse in BD.

Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1.

Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island. This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD). In heterozygotes, HDL-C levels are about one-half those of normal individuals. Impaired cholesterol efflux from macrophages leads to the presence of foam cells throughout the body, which may explain the increased risk of coronary heart disease in some TD families. We report here refining of our previous linkage of the TD gene to a 1-cM region between markers D9S271 and D9S1866 on chromosome 9q31, in which we found the gene encoding human ATP cassette-binding transporter 1 (ABC1). We also found a change in ABC1 expression level on cholesterol loading of phorbol ester-treated THP1 macrophages, substantiating the role of ABC1 in cholesterol efflux. We cloned the full-length cDNA and sequenced the gene in two unrelated families with four TD homozygotes. In the first pedigree, a 1-bp deletion in exon 13, resulting in truncation of the predicted protein to approximately one-fourth of its normal size, co-segregated with the disease phenotype. An in-frame insertion-deletion in exon 12 was found in the second family. Our findings indicate that defects in ABC1, encoding a member of the ABC transporter superfamily, are the cause of TD.

Depression symptom outcomes and re-engagement among VA patients who discontinue care while symptomatic.

OBJECTIVE: Evaluate outcomes of Veterans who discontinued treatment with at least moderate ongoing depressive symptoms. METHOD: Veterans with elevated depression symptoms from 29 Department of Veterans Affairs facilities completed baseline surveys and follow-up assessments for one year. Analyses examined rates and predictors of treatment discontinuation, treatment re-engagement, and subsequent symptoms among patients who remained out of care. RESULTS: A total of 242 (17.8%; n = 1359) participants discontinued treatment while symptomatic, with Black participants, participants with less severe depression, and participants receiving only psychotherapy (versus combined psychotherapy and antidepressant medications) discontinuing at higher rates. Among all participants who discontinued treatment (n = 445), 45.8% re-engaged within the following six months with participants receiving combined treatment re-engaging at higher rates. Of participants who discontinued while symptomatic within the first 6 months of the study and did not return to care (n = 112), 68.8% remained symptomatic at 12 months. Lower baseline treatment expectancy and greater depression symptom severity were associated with remaining symptomatic while untreated. CONCLUSIONS: Black race, lower symptom severity, and treatment modality may help identify patients at higher risk for discontinuing care while symptomatic, whereas patients with lower treatment expectations may be at greater risk for remaining out of care despite continuing symptoms.

Post-discharge tobacco cessation rates among hospitalized US veterans with and without diabetes.

AIMS: Smoking is a major risk factor for cardiovascular complications among patients with diabetes. Hospitalization has been shown to enhance cessation rates. The purpose of this study was to compare 6-month post-hospitalization tobacco cessation rates among US veterans with and without diabetes. METHODS: This was a longitudinal study among inpatient veterans who used tobacco in the past month (n = 496). Patients were recruited and surveyed from three Midwestern Department of Veterans Affairs hospitals during an acute-care hospitalization. They were also asked to complete a follow-up survey 6 months post-discharge. Bivariate- and multivariable-adjusted analyses were conducted to determine differences in tobacco cessation rates between patients with and without a diagnosis of diabetes. RESULTS: The mean age of patients was 55.2 years and 62% were white. Twenty-nine per cent had co-morbid diabetes. A total of 18.8% of patients with diabetes reported tobacco cessation at 6 months compared with 10.9% of those without diabetes (P = 0.02). Cotinine-verified cessation rates were 12.5 vs. 7.4% in the groups with and without diabetes, respectively (P = 0.07). Controlling for psychiatric co-morbidities, depressive symptoms, age, self-rated health and nicotine dependence, the multivariable-adjusted logistic regression showed that patients with diabetes had three times higher odds of 6-month cotinine-verified tobacco cessation as compared with those without diabetes (odds ratio 3.17, P = 0.005). CONCLUSIONS: Post-hospitalization rates of smoking cessation are high among those with diabetes. Intensive tobacco cessation programmes may increase these cessation rates further.

Factors influencing the efficacy of two injections of a pandemic 2009 influenza A (H1N1) nonadjuvanted vaccine in systemic lupus erythematosus.

OBJECTIVE: To assess the factors influencing the efficacy of 2 injections of a pandemic 2009 influenza A (H1N1) vaccine in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a single-center, observational prospective study of 111 patients who were vaccinated with a monovalent, inactivated, nonadjuvanted, split-virus vaccine during December 2009 and January 2010 and received a second dose of vaccine 3 weeks later. The antibody response was evaluated using the hemagglutination inhibition assay according to the guidelines recommended for the pandemic vaccine, consisting of 3 immunogenicity criteria (i.e., a seroprotection rate of 70%, a seroconversion rate of 40%, and a geometric mean ratio [GMR] of 2.5). RESULTS: The 3 immunogenicity criteria were met on day 42 (seroprotection rate 80.0% [95% confidence interval (95% CI) 72.5-87.5%], seroconversion rate 71.8% [95% CI 63.4-80.2%], and GMR 10.3 [95% CI 2.9-14.2]), while only 2 criteria were met on day 21 (seroprotection rate 66.7% [95% CI 57.9-75.4%], seroconversion rate 60.4% [95% CI 51.3-69.5%], and GMR 8.5 [95% CI 3.2-12.0]). The vaccine was well tolerated. Disease activity, assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index, the British Isles Lupus Assessment Group score, and the Systemic Lupus Activity Questionnaire, did not increase. In the multivariate analysis, vaccination failure was significantly associated with immunosuppressive treatment or a lymphocyte count of ≤ 1.0 × 109/liter. The second injection significantly increased the immunogenicity in these subgroups, but not high enough to fulfill the seroprotection criterion in patients receiving immunosuppressive treatment. CONCLUSION: Our findings indicate that the efficacy of the vaccine was impaired in patients who were receiving immunosuppressive drugs or who had lymphopenia. A second injection increased vaccine immunogenicity without reaching all efficacy criteria for a pandemic vaccine in patients receiving an immunosuppressive agent. These results open possibilities for improving anti-influenza vaccination in SLE.

[Heart involvement in systemic lupus erythematosus and antiphospholipid syndrome]. / Cœur et médecine interne : lupus systémique et syndrome des antiphospholipides.

Cardiac involvement in systemic lupus (SL) and antiphospholipid syndrome (APS) can be due to variables and involve different presentations. Pericarditis is the most common lupus manifestation and occurs in 16% to 25% of patients. While corticosteroids are usually very effective, colchicine may avoid steroids and prevent relapse. Myocarditis during SL is rare and often inaugural. They may manifest as chest pain, acute heart failure, arrhythmias or conduction disturbances, and may progress to dilated cardiomyopathy and/or permanent heart failure. Their prognosis is however generally good, even in the absence of treatment with cyclophosphamide for the less serious forms. Finally, coronary involvement in SL is most often due to atherosclerotic, thrombotic origin (generally in the context of associated APS), and exceptionally explained by coronary vasculitis. During APS, valve disease is frequent and usually asymptomatic. Thrombotic damage can be (1) coronary, typically manifesting as a myocardial infarction in a young subject with healthy coronary arteries, (2) much more rarely intracardiac, or (3) microcirculatory, generally as part of a catastrophic antiphospholipid syndrome (CAPS) leading to a multiorgan failure. Finally, iatrogenic cardiac manifestations can exceptionally be seen during treatment with cyclophosphamide or antimalarials characterized by conduction disorders and/or heart failure.

EULAR recommendations for the management of systemic lupus erythematosus with neuropsychiatric manifestations: report of a task force of the EULAR standing committee for clinical affairs.

OBJECTIVES: To develop recommendations for the diagnosis, prevention and treatment of neuropsychiatric systemic lupus erythematosus (NPSLE) manifestations. METHODS: The authors compiled questions on prevalence and risk factors, diagnosis and monitoring, therapy and prognosis of NPSLE. A systematic literature search was performed and evidence was categorised based on sample size and study design. RESULTS: Systemic lupus erythematosus (SLE) patients are at increased risk of several neuropsychiatric manifestations. Common (cumulative incidence > 5%) manifestations include cerebrovascular disease (CVD) and seizures; relatively uncommon (1-5%) are severe cognitive dysfunction, major depression, acute confusional state (ACS), peripheral nervous disorders psychosis. Strong risk factors (at least fivefold increased risk) are previous or concurrent severe NPSLE (for cognitive dysfunction, seizures) and antiphospholipid antibodies (for CVD, seizures, chorea). The diagnostic work-up of suspected NPSLE is comparable to that in patients without SLE who present with the same manifestations, and aims to exclude causes unrelated to SLE. Investigations include cerebrospinal fluid analysis (to exclude central nervous system infection), EEG (to diagnose seizure disorder), neuropsychological tests (to assess cognitive dysfunction), nerve conduction studies (for peripheral neuropathy) and MRI (T1/T2, fluid-attenuating inversion recovery, diffusion-weighted imaging, enhanced T1 sequence). Glucocorticoids and immunosuppressive therapy are indicated when NPSLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis, ACS) and in the presence of generalised lupus activity. Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic CVD. CONCLUSIONS: Neuropsychiatric manifestations in SLE patients should be first evaluated and treated as in patients without SLE, and secondarily attributed to SLE and treated accordingly.

Serum cartilage oligomeric matrix protein (COMP) level is a marker of disease activity in relapsing polychondritis.

OBJECTIVES: Relapsing polychondritis (RP) is a rare and severe disease which may lead to destruction of elastic cartilages. Until now, no reliable biomarker of disease activity in RP has been available. This study was designed to measure serum levels of cartilage biomarkers during both active and inactive phases of the disease. METHODS: Serum levels of cartilage oligomeric matrix protein (COMP), chondroitin sulfate 846 epitope (CS846) of proteoglycan aggrecan and collagen type II collagenase cleavage neoepitope (C2C) were measured retrospectively in 21 subjects with RP. The Wilcoxon matched-pairs signed-rank test was used for statistical comparisons of biomarker levels in active and inactive phases of RP. RESULTS: Only the serum level of COMP was significantly increased during disease flares. Steroids did not alter the serum cartilage-related biomarker levels. However, during the active phase, C2C levels were significantly higher in steroid treated patients compared with non-steroid treated patients. CONCLUSIONS: This study suggests that serum COMP level may be useful for monitoring disease activity of RP. Further prospective studies are required to confirm this result.

Coronavirus rotational diffusivity.

Just 11 weeks after the confirmation of first infection, one team had already discovered and published [D. Wrapp et al., "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation," Science 367(6483), 1260-1263 (2020)] in exquisite detail about the new coronavirus, along with how it differs from previous viruses. We call the virus particle causing the COVID-19 disease SARS-CoV-2, a spherical capsid covered with spikes termed peplomers. Since the virus is not motile, it relies on its own random thermal motion, specifically the rotational component of this thermal motion, to align its peplomers with targets. The governing transport property for the virus to attack successfully is thus the rotational diffusivity. Too little rotational diffusivity and too few alignments are produced to properly infect. Too much, and the alignment intervals will be too short to properly infect, and the peplomer is wasted. In this paper, we calculate the rotational diffusivity along with the complex viscosity of four classes of virus particles of ascending geometric complexity: tobacco mosaic, gemini, adeno, and corona. The gemini and adeno viruses share icosahedral bead arrangements, and for the corona virus, we use polyhedral solutions to the Thomson problem to arrange its peplomers. We employ general rigid bead-rod theory to calculate complex viscosities and rotational diffusivities, from first principles, of the virus suspensions. We find that our ab initio calculations agree with the observed complex viscosity of the tobacco mosaic virus suspension. From our analysis of the gemini virus suspension, we learn that the fine detail of the virus structure governs its rotational diffusivity. We find the characteristic time for the adenovirus from general rigid bead-rod theory. Finally, from our analysis of the coronavirus suspension, we learn that its rotational diffusivity descends monotonically with its number of peplomers.

Antimyeloperoxidase antibodies are a useful marker of disease activity in antineutrophil cytoplasmic antibody-associated vasculitides.

OBJECTIVE: To evaluate the relevance of monitoring antimyeloperoxidase antibody levels in the management of antimyeloperoxidase-associated vasculitides. METHODS: Thirty-eight patients with antimyeloperoxidase-associated vasculitides were included: microscopic polyangiitis (n = 18), Wegener's granulomatosis (n = 15) and Churg-Strauss syndrome (n = 5). Baseline characteristics and outcomes were recorded. Serial measurements of antimyeloperoxidase antibody levels were performed (ELISA, positive > or = 20 IU/ml). RESULTS: All patients achieved vasculitis remission after a mean time of 2.0 months (SD 0.9), with a significant decrease in the mean antimyeloperoxidase antibody level at remission (478 vs 41 IU/ml (SD 598 vs 100); p<0.001). Twenty-eight (74%) patients became antimyeloperoxidase antibody negative. After a mean follow-up of 54 months (SD 38), 12 cases of clinical relapse occurred in 11/38 (29%) patients. Relapses were associated with an increase in antimyeloperoxidase antibody levels in 10/11 (91%) patients (34 vs 199 IU/ml (88 vs 314); p = 0.002). The reappearance of antimyeloperoxidase antibodies after achieving negative levels was significantly associated with relapse (odds ratio 117; 95% CI 9.4 to 1450; p<0.001). Antimyeloperoxidase antibodies showed a positive predictive value of 90% and a negative predictive value of 94% for relapse of vasculitis. Up to 60% of cases of relapse occurred less than 12 months after the reappearance of antimyeloperoxidase antibodies. Relapse-free survival was significantly worse for patients who exhibited a reappearance of antimyeloperoxidase antibodies than in those with persistent negative antimyeloperoxidase antibodies (p<0.001). The antimyeloperoxidase antibodies serum level was strongly correlated with the Birmingham vasculitis activity score and the disease extent index (r = +0.49; p = 0.002). CONCLUSION: Through monitoring, antimyeloperoxidase antibodies are a useful marker of disease activity and a good predictor of relapse in antimyeloperoxidase-associated vasculitides.

Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders.

OBJECTIVE: To evaluate the relevance of serum-free light chain (FLC) assessment in hepatitis C virus (HCV)-related lymphoproliferative disorders, including mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL). PATIENTS AND METHODS: A total of 59 patients infected with HCV were prospectively followed, including patients without MC (n = 17), with asymptomatic MC (n = 7) and with MC vasculitis (n = 35, 9 of whom had B-NHL). Clinical and biological data were recorded at the time of the initial evaluation and at the end of follow-up. Serum FLC quantitation was carried out using a serum FLC assay. RESULTS: The mean (SD) serum kappa FLC level was higher in patients with asymptomatic MC (27.9 (8.6) mg/litre), MC vasculitis (36.7 (46.2) mg/litre) and B-NHL (51.3 (78.3) mg/litre) than without MC (21.7 (17.6) mg/litre) (p = 0.047, 0.025 and 0.045, respectively). The mean serum FLC ratio was higher in patients with MC vasculitis (2.08 (2.33)) and B-NHL (3.14 (3.49)) than in patients without MC (1.03 (0.26)) (p = 0.008). The rate of abnormal serum FLC ratio (>1.65) correlated with the severity of HCV-related B cell disorder: 0/17 (0%) without MC, 0/7 (0%) asymptomatic MC, 6/26 (23%) MC vasculitis without B-NHL and 4/9 (44%) B-NHL (p = 0.002). Serum kappa FLC levels and the serum FLC ratio correlated with the cryoglobulin level (r = 0.32, p<0.001 and r = 0.25, p = 0.002, respectively) and the severity of the B cell disorder (r = 0.26, p = 0.045 and r = 0.41, p = 0.001, respectively). Among patients with an abnormal serum FLC ratio at baseline, the FLC ratio correlated with the virological response to HCV treatment. CONCLUSIONS: In patients infected with HCV, an abnormal serum FLC ratio appears to be a very interesting marker, as it is consistently associated with the presence of MC vasculitis and/or B-NHL. After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation.

Pathological features of temporal arteries in patients with giant cell arteritis presenting with permanent visual loss.

BACKGROUND: Permanent visual loss (PVL) is the most feared complication of giant cell arteritis (GCA), and its risk factors are still unclear. OBJECTIVES: The aim of our study was to assess the pathological features predictive of PVL on temporal artery biopsy (TAB) specimens in patients with GCA. METHODS: The slides of 391 TAB specimens from patients with GCA were reviewed by two pathologists without clinical information. RESULTS: A total of 29 patients (26 females and 3 males, mean age 78.3 years) presented with unilateral PVL at the onset of the disease, and 362 patients (258 females, 104 males, mean age 74.7 years), did not. The pathological features strongly predictive for PVL were the presence (p = 0.003), number (p = 0.001) and aggregates of giant cells (p = 0.001), presence of plasmocytes (p = 0.002), thickened intima (p = 0.007), neoangiogenesis (p = 0.001) and degree of arterial occlusion (p = 0.006). Presence of neutrophils, eosinophils, parietal necrosis, calcification in the arterial wall and disruption of the internal elastic membrane were similar in both groups. Total obstruction of the arterial lumen by a thrombus, intensity of the inflammatory cells infiltration and inflammation of small vessels, nerves and veins surrounding the temporal artery were not associated with blindness. In multivariate analysis, only giant cells remained significantly associated with PVL. CONCLUSION: Giant cells are strongly associated with PVL, with a significant gradient between great risk and large number of giant cells. However, PVL was neither associated with the intensity of the inflammatory infiltrate, nor with the presence of arterial thrombosis.