The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV).
We conducted a retrospective cohort study of all GPA or MPA, ...according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates.
125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ± 78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12–36.56, and adjusted HR 10.3; 95% CI 1.02–104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34–1.83).
AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.
•Patients with AAV have a four times more risk of ischemic stroke or coronary artery disease that in the general population.•Cardiovascular mortality in associated-ANCA vasculitis (AAV) patients is 1.5 times more than in the general population.•Monitoring for this complication and vigilance in modifying risk factors are warranted in this patient population.
Double-positive patients (DPPs), combining serum and/or histological findings for glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic antibodies (ANCAs), are rare and poorly ...described. This study aimed to compare characteristics between DPPs and ANCA-associated vasculitis (AAV) patients with severe renal involvement.
This retrospective multicentre study compared 33 DPPs and 45 AAV patients with severe renal involvement (serum creatinine > 300 μmol/L), all with biopsy-proven nephropathy.
All DPPs (including 18% exhibiting negative serum anti-GBM antibodies) presented severe acute kidney failure with histological GBM involvement. Compared to AAV patients, they had higher serum creatinine (719 vs 501 μmol/L; p = 0.006) and a higher proportion of patients requiring initial renal replacement therapy (82% vs 36%; p < 0.001). Berden classification differed significantly (p = 0.003), with more crescentic glomerulonephritis and fewer sclerotic lesions in DPPs. One-year renal survival was significantly lower in DPPs than in AAV patients (27% vs 64%; p < 0.0002). With comparable proportions of ANCA subtypes (two-thirds with anti-myeloperoxidase autoantibodies), numbers of extrarenal manifestations (mostly pulmonary in two-thirds), remission-inducing immunosuppressants, and median follow-ups (3 years) between groups, relapse rates were similar: 9.1% of DPPs and 10% of AAV patients.
Although DPPs have features of both kinds of vasculitis, the anti-GBM component is the dominant phenotype, with more severe renal presentation and prognosis compared to AAV patients with severe renal failure. Simultaneous testing of both antibodies and systematically performed renal biopsy should be recommended in all rapidly progressing glomerulonephritis patients to recognize this difficult-to-treat, rare disease.
Temporo-mandibular joint dysfunction can be painful and disabling. In some cases, it is refractory to classical treatment. Intra-articular Botulinum toxin injections have been shown to have an ...anti-inflammatory and analgesic effect. The aim of this study was to evaluate the effectiveness of such injections on severe, refractory temporo-mandibular joint pain. This was a retrospective study. Patients were included if they still had joint pain≥5 on a Visual Analogue Scale following completion of all other treatments. A complete treatment protocol (including physiotherapy, tongue splints, intra muscular injections of Botulinum toxin and injections of hyaluronic acid, excluding surgery) having being done before the injection of 30 Botox* units (Botulinum toxin A), the treatment being considered clinically successful if the Visual Analogue Scale decreases by at least 2 points. Seventy-seven patients were included. Sixty-six percent of patients have a significant reduction in pain at 1 month which lasted at least until 3 months. Mouth opening and quality of life also improved. Moreover, no complications were reported. Further randomized, controlled studies are needed to confirm the results, however this study suggests intra-articular injection of Botulinum toxin is a safe and effective treatment for severe, refractory temporo-mandibular joint pain, avoiding surgery.
Cryofibrinogenemia is an unknown disorder and studies dedicated to it are limited. The aim of our study was to report on the incidence, clinical manifestations and associated diseases in patients ...with isolated cryofibrinogenemia.
This is a retrospective single-center study. Patients included in this study had a positive and isolated detection of cryofibrinogen between January 1st, 2011 and December 31st, 2012. Identification was possible through the database of the laboratory of immunology.
Two hundred and eighty-one consecutive orders of cryofibrinogenemia were identified. Seventy-three patients had a positive detection of cryofibrinogenemia. Among them, 12 had an isolated cryofibrinogenemia and sixty-one patients (84%) had concomitant cryofibrinogenemia and cryoglobulinemia. The mean age was 59±19years. Seven patients were female (58%). Cutaneous manifestations were present in half case. Peripheral nerve involvement was present in 5 cases (42%) and rheumatic manifestations in 4 patients (33%). A thrombotic event was reported in 7 patients (58%). Renal impairment was present in 7 patients. The median cryofibrinogen concentration was 254±304mg/L. Five patients had a secondary cryofibrinogenemia. The most often prescribed treatment was corticosteroids.
Cryofibrinogenemia is an unknown disorder. Testing for cryoglobulinemia is more frequent than for cryofibrinogenemia whereas clinical manifestations are similar. Detection of cryofibrinogen is positive in most of the cases, with an important prevalence of thrombotic events in this population. This study confirms the importance of conducting prospective studies on cryofibrinogenemia.
The purpose of this study was to evaluate the renal side-effects of adefovir therapy in kidney-transplant (KT) recipients with chronic hepatitis B virus (HBV) infection, who have become resistant to ...lamivudine therapy.
11 kidney-transplant (KT) patients (10 men, 1 woman, median age 54 (46 - 67) years) had lamivudine-resistant chronic HBV infection. With respect to HBV markers, all were HBs Ag-positive, 8 were HBe Ag-negative/HBe antibody- (Ab) positive, i.e. precore mutant, and 3 were HBe Ag-positive/HBe Ab-negative. They were all given adefovir at 10 mg/d (3 cases) or 5 mg/d (6 cases) or 2.5 mg/d (2 cases) according to creatinine clearance.
Compared to baseline without adefovir therapy, at last follow-up, adefovir therapy was associated, at 1 and 2 years post therapy, with a significant decrease in aspartate (AST) (28 (17 - 53), 28 (10 - 79) vs. 58 (24 - 1,282) IU/l, p = 0.001), alanine (ALT) (38 (13 - 55), 36 (17 - 92) vs. 72 (31 - 1,594) IU/l, p = 0.0032 aminotransferase levels, and gammaGT (31 (14 - 51), 25 (14 - 196) vs. 44 (25 - 742) IU/l, p = 0.03). With respect to HBV DNA, when compared to baseline, there was a significant decrease at both years 1 and 2 post therapy (p = 0.01). With respect to KT function at 2 years after starting adefovir, there was a significant increase in serum creatinine from 125 (+/- 35) to 141 (+/- 32) micromol/l, (p = 0.02) and a significant increase in 24-h proteinuria. With respect to renal tubular parameters, as compared to baseline without adefovir therapy, one year after adefovir therapy was commenced there was a significant decrease in urinary pH from 6.6 (+0.6) to 5.65 (+/- 0.7); p = 0.03, a significant decrease in bicarbonaturia (from 0.33 +/- 0.7 to 0.1 +/- 0.3 mmol/h, p = 0.01), an increase in urinary excretion of H+ (1.79 (+/- 1.33) to 2.44 (+/- 1.18) mmol/l (p = 0.03)), a significant decrease in phosphatemia (0.82 +/- 0.19 vs. 0.65 +/- 0.13 mmol/l, p = 0.04) and a significant decrease in phosphaturia threshold, a significant decrease in tubular phosphorus reabsorption (75.5 +/- 9.4% vs. 61.8 +/- 16%, p = 0.05), and a significant increase in the phosphorus index of excretion (0.18 +/- 0.114 vs. 0.35 +/- 0.164, p = 0.01).
We have demonstrated that low-dosage adefovir therapy in kidney-transplant patients is relatively safe as far as renal parameters are concerned, even though we observed a slight impairment of renal proximal-tubular function.
The scleroderma renal crisis is characterized by acute onset of severe hypertension and by rapidly progressive hyperreninemic renal failure. There is, however, a very limited subset of patients with ...rapidly progressive renal failure who remain normotensive and develop ANCA-positive crescentic glomerulonephritis. We report a case of normotensive acute renal failure secondary to anti-MPO antibody-associated crescentic glomerulonephritis in a patient with diffuse systemic sclerosis. She was referred to our department with normal blood pressure and no extrarenal clinical manifestation ofvasculitis. She presented with rapidly progressive renal failure, microscopic hematuria and minimal proteinuria. P-ANCA were positive by immunofluorescence, with ELISA-confirmed specificity for myeloperoxidase. Renal biopsy revealed typical features of pauciimmune glomerulonephritis with crescent formation and fibrinoid necrosis. The patient was initially treated with i.v. cyclophosphamide only. Because of ongoing deteriorating renal function, additional treatment with intravenous pulses of methylprednisolone followed by oral prednisone was started and allowed renal function improvement. After 9 months, serum creatinine had almost returned to normal level with minimal proteinuria, no hematuria and negative ANCA testing. Control kidney biopsy only revealed scar lesions. The association of ANCA-positive crescentic glomerulonephritis and systemic sclerosis is a very rare event. Treatment with intravenous cyclophosphamide and corticosteroids allows rapid and long-term improvement of renal function. The onset of typical scleroderma renal crisis triggered by high-dose corticosteroids is unlikely but requires a close follow-up of patients with overlapping systemic sclerosis. Diagnosis and treatment are discussed and previously published cases are reviewed.
Following accidental release of valproate into ambient air during manufacture at a French production site in 2018, concerns were raised for inhabitants of the surrounding area. As no toxicological ...reference value (TRV) was available, the risks could not be properly assessed. The French Agency for Food, Environmental and Occupational Health and Safety (ANSES) was mandated to determine a TRV by inhalation to be used for risk assessment. Major congenital malformations (MCMs) in offsprings of mothers exposed to valproate during pregnancy have been reported in international scientific literature. As these adverse effects were the most sensitive effect identified, they were retained as the critical effect to be used for the TRV. The data from a robust registry on MCMs established by the International Registry of Antiepileptic Drugs and Pregnancy (EURAP) were modellized and support a strong DRR between the prevalence of MCMs in the fetus and in utero exposure. A benchmark dose (BMD) was then calculated as the dose that may trigger a 5% increase in this risk. A lower 95% confidence limit (BMD5%L95%) of 2.26 mg/kg/day, leading to an oral TRV of 0.08 mg/kg/day and a respiratory TRV of 0.26 mg.m-3 after applying an uncertainty factor of 30, was determined.
•A scientific literature review on the adverse effects of valproate as environmental contaminant has been performed.•Reprotoxic effects were identified as the critical effect to be considered to derive a reference value.•A human study characterized by a dose-response relationship was selected as the key study.•Reference values by inhalation based on the BMD approach were calculated for workers.
A large share of the global forest restoration potential is situated in artificial ‘unstable’ mesic African savannas, which could be restored to higher carbon and biodiversity states if protected ...from human‐induced burning. However, uncertainty on recovery rates in protected unstable savannas impedes science‐informed forest restoration initiatives. Here, we quantify the forest restoration success of anthropogenic fire exclusion within an 88‐ha mesic artificial savanna patch in the Kongo Central province of the Democratic Republic of the Congo (DR Congo). We found that aboveground carbon recovery after 17 years was on average 11.40 ± 0.85 Mg C ha−1. Using a statistical model, we found that aboveground carbon stocks take 112 ± 3 years to recover to 90% of aboveground carbon stocks in old‐growth forests. Assuming that this recovery trajectory would be representative for all unstable savannas, we estimate that they could have a total carbon uptake potential of 12.13 ± 2.25 Gt C by 2100 across DR Congo, Congo and Angola. Species richness recovered to 33.17% after 17 years, and we predicted a 90% recovery at 54 ± 2 years. In contrast, we predicted that species composition would recover to 90% of old‐growth forest composition only after 124 ± 3 years. We conclude that the relatively simple and cost‐efficient measure of fire exclusion in artificial savannas is an effective nature‐based solution to climate change and biodiversity loss. However, more long‐term and in situ monitoring efforts are needed to quantify variation in long‐term carbon and diversity recovery pathways. Particular uncertainties are spatial variability in socio‐economics and growing conditions as well as the effects of projected climate change.
Fire exclusion in an artificial savanna in the DR Congo resulted in rapid aboveground carbon recovery, at 11.40 ± 0.85 Mg C ha−1 after 17 years and reaching 90% of aboveground carbon stocks in old‐growth forests after 112 ± 3 years. Species richness is predicted to recover even faster, reaching 90% of old‐growth values after 54 ± 2 years. We conclude that the relatively simple and cost‐efficient measure of fire exclusion in artificial savannas is an effective nature‐based solution to climate change and biodiversity loss, but more long‐term monitoring efforts are needed to quantify variation in recovery pathways.
