Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging ...is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging.
Systemic sclerosis (SSc) is associated with a variability of mortality rates in the literature.
To determine the mortality and its predictors in a long-term follow-up of a bi-centric cohort of SSc ...patients.
A retrospective observational study by systematically analyzing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. Standardized Mortality Ratio (SMR), mortality at 1, 3, 5, 10, and 15 years of disease and causes of death were described. Predictors of mortality using Cox regression were assessed.
Three hundred seventy-five patients were included: 63 with diffuse cutaneous SSc, 279 with limited cutaneous SSc, and 33 with sine scleroderma. The SMR ratio was 1.88 (95% CI 1.46-1.97). The overall survival rates were 97.6% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years, and 61.3% at 15 years. Sixty-nine deaths were recorded. 46.4% were SSc related deaths secondary to interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%), and digestive tract involvement (18.8%). 53.6% were non-related to SSc: cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified: carbon monoxide diffusing capacity (DLCO) < 70% (HR=3.01; p=0.0053), C-reactive protein (CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012), and the fact of being male (HR=3.25; p=0.0004).
Long-term data confirmed high mortality of SSc. Male sex, DLCO <70%, cardiac involvement, and CRP> 5mg/l were identified as independent predictors of mortality.
To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).
We conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors ...associated with response to tocilizumab (assessed using NIH score).
Forty-six patients with TA were included, with a median age of 43 years 29–54, and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 2–3 at baseline to 0 0–1 and 0 at 3 and 6 months, respectively; p < 0.0001). The daily prednisone dose also decreased from 15 mg 8–19 at baseline to 4 mg 5–21 and 5 mg 4.5–9 at 3 and 6 months, respectively (p < 0.0001) under tocilizumab. The overall tocilizumab failure free survival was 81% CI 95%; 0.7–0.95, 72% CI 95%; 0.55–0.95 and 48% CI 95%; 0.2–0.1 at 12, 24 and 48 months, respectively. The presence of constitutional symptoms (HR 5.6 CI 95%; 1.08–29, p = 0.041), and C-reactive protein level (HR 1.16 CI 95%; 1.01–1.31, P = 0.003) at the time of tocilizumab initiation were significantly associated with tocilizumab event-free survival. The event-free survival was significantly better under tocilizumab therapy in comparison to DMARDs (p = 0.02).
This large multicenter study shows that tocilizumab is efficient and may reduce the incidence of relapses in TA.
•Tocilizumab can lead patients TA to remission in 80%, have steroid sparing effect and a good safety profile.•Tocilizumab can be used in monotherapy and as first line therapy.•Tocilizumab can be used in monotherapy and is effective as first line therapy.
Fabry disease is a frequent lysosomal storage disorder secondary to the deficiency of alpha-galactosidase A enzyme. This X-linked genetic disease realizes progressive and systemic manifestations that ...affect both male and female. Fabry disease may present as "classical", as "late-onset" or "non-classical" forms. Symptoms and organ involvements of classical Fabry disease are acral pain crisis, cornea verticillata, hypertrophic cardiomyopathy, stroke and chronic kidney disease with proteinuria. Other common symptoms are often poorly recognized, such as gastrointestinal or ear involvements. In classical Fabry disease, symptoms first appear during childhood or during teenage years in males, but later in females. Patients with non-classical or late-onset Fabry disease have delayed manifestations or a single-organ involvement. Diagnosis is therefore difficult when classical organ involvements are missing, in paucisymptomatic patients or in late-onset forms. Recognition of Fabry disease is important because effective treatments are available. They have to be prescribed early. In male, diagnosis is made with alpha-galactosidase A enzyme activity dosage in leukocyte, that is very low or null in classical forms and under 30 percent in late-onset forms. Diagnosis is more challenging in females who may express normal residual enzyme activity. Other plasmatic biomarkers, such as lyso-globotriaosylceramide are interesting, especially in females. In this review, we aimed to summarize main clinical manifestations of Fabry disease to know when to evoke Fabry disease and propose a practical diagnosis algorithm to know how to diagnose.
Since its introduction, Building Information Modelling has evolved into a major technology in the construction industry, where information flows play a major role. However, the very presence of waste ...within these flows prevents the technology from reaching its full potential. This paper aims to develop a taxonomy focused on the sources of waste within information flows in BIM projects, as existing taxonomies focus primarily on work and material flows. Using a collaborative design science research approach, the study was divided into two phases: first, semi-structured interviews were used to collect data on BIM practices. The data was then used to identify similarities and contradictions in the information flows using process maps. Second, the ShareLab approach was used to validate the findings through a common agreement. The paper’s main contribution is the taxonomy of sources of waste in BIM project information flows, as it closes knowledge gaps in one of the main flows of construction projects. Another contribution is its use of a new approach to validate an artefact in a Design Science Research methodology named the ShareLab approach.
Abstract Background Cryofibrinogenemia is frequently associated with cryoglobulinemia. The aim of this study was to determine the characteristics associated with the presence of cryofibrinogenemia in ...patients with cryoglobulinemic vasculitis. Methods This was a single-center retrospective study that included patients with cryoglobulinemic vasculitis who were tested for cryofibrinogen at a tertiary referral center between January 1, 2011 and December 31, 2012. Twenty-nine patients fulfilled the CryoVas (cryoglobulinemic vasculitis) Survey criteria for cryoglobulinemic vasculitis. Eighteen patients had a detectable cryofibrinogen (CF-positive) and 11 had no detectable cryofibrinogen (CF-negative). Median cryoglobulin levels were 89 ± 129 mg/L in the CF-positive group and 68 ± 82 mg/L in the CF-negative group ( P = .32). Median cryofibrinogen level was 70 ± 174 mg/L. Clinical manifestations were similar in both groups. Cancers and hematological disorders were more frequent among CF-positive patients (39% vs 0%, P = .026). Levels of alpha-1 and alpha-2 globulinemia were higher in the CF-positive group. Cryofibrinogenemia ≥ 100 mg/L was associated with cryoglobulinemic vasculitis (odds ratio OR 2.86; 95% confidence interval CI, 1.06-7.73) in cryoglobulinemic patients. Presence of cryofibrinogenemia was associated with use of corticosteroids, immunosuppressants, or plasmapheresis in cryoglobulinemic vasculitis patients (OR 22.7; 95% CI, 2.02-256.44). Conclusions Our results strongly suggest that presence of cryofibrinogenemia is associated with a more severe phenotype among patients with cryoglobulinemic vasculitis.
Background:
Few studies of daily practice for patients with giant cell arteritis (GCA) are available. This French study aimed to describe the characteristics and management of GCA in a real-life ...setting.
Methods:
Cross-sectional, non-interventional, multicenter study of patients ≥50 years old who consulted hospital-based specialists for GCA and were under treatment. Patient characteristics and journey, diagnostic methods and treatments were collected. Descriptive analyses were performed.
Results:
In total, 306 patients (67% females, mean age 74 ± 8 years old) were recruited by 69 physicians (internists: 85%, rheumatologists: 15%); 13% of patients had newly diagnosed GCA (diagnosis-to-visit interval <6 weeks). Overall median disease duration was 13 months (interquartile range 5–26). Most patients were referred by general practitioners (56%), then ophthalmologists (10%) and neurologists (7%). Most common comorbidities were hypertension (46%), psychiatric disorders (10%), dyslipidemia (12%), diabetes (9%), and osteoporosis (6%). Initial GCA presentations included cranial symptoms (89%), constitutional symptoms (74%), polymyalgia rheumatica (48%), and/or other extra-cranial manifestations (35%). Overall, 85, 31, 26, and 30% of patients underwent temporal artery biopsy, high-resolution temporal artery Doppler ultrasonography,
18
FDG-PET, and aortic angio-CT, respectively. All patients received glucocorticoids, which were ongoing for 89%; 29% also received adjunct medication(s) (methotrexate: 19%, tocilizumab: 15%). A total of 40% had relapse(s); the median time to the first relapse was 10 months. Also, 37% had comorbidity(ies) related to or aggravated by glucocorticoids therapy.
Conclusion:
This large observational study provides insight into current medical practices for GCA. More than one third of patients had comorbidities related to glucocorticoid therapy for a median disease duration of 13 months. Methotrexate and tocilizumab were the most common adjunct medications.
We aimed to analyze patients with acute and chronic joint involvements in sarcoidosis.
This is a retrospective multicenter analysis of patients with proven sarcoidosis, as defined by clinical, ...radiological, and histological criteria, with at least one clinical and/or ultrasonographic synovitis.
Thirty-nine patients with sarcoid arthropathy were included, and among them 19 had acute sarcoidosis (Lofgren's syndrome). Joint involvement and DAS44-CRP were not significantly different in acute and chronic sarcoid arthropathies. Acute forms were more frequent than chronic sarcoid arthropathy in Caucasians, without any difference of sex or age between these 2 forms. Joint involvement was frequently more symmetrical in acute than chronic forms (100 vs. 70%;
< 0.05), with a more frequent involvement in wrists and ankles in acute forms, whereas the tender and swollen joint counts and the DAS44-CRP were similar between the 2 groups. Skin lesions were significantly more frequent in patients with acute forms 17 (89%) vs. 5 (25%);
< 0.05 and were erythema nodosum in all patients with Löfgren's syndrome and sarcoid skin lesions in those with chronic sarcoidosis. Among 20 patients with chronic sarcoidosis, treatment was used in 17 (85%) cases, and consisted in NSAIDs alone (
= 5; 25%), steroids alone (
= 5; 25%), hydroxychloroquine (
= 2; 20%), methotrexate (
= 3; 15%), and TNF inhibitors (
= 2; 10%). A complete/partial joint response was noted in 14 (70%) cases with a DAS44-CRP reduction of 2.07 1.85-2.44 (from 3.13 2.76-3.42 to 1.06 0.9-1.17;
< 0.05).
Sarcoid arthropathies have different clinical phenotypes in acute and chronic forms and various treatment regimens such as hydroxychloroquine and methotrexate could be used in chronic forms.
Cryofibrinogenemia Michaud, Martin; Pourrat, Jacques
Journal of clinical rheumatology
19, Issue:
3
Journal Article
Peer reviewed
Cryofibrinogenemia is a cryoprotein that was first identified in 1955 by Korst and Kratochvil. Unlike cryoglobulin, the precipitate forms only in plasma and not in the serum. The presence of ...cryofibrinogen in plasma can be asymptomatic. Cryofibrinogenemia is considered a rare disorder: its prevalence varies from 0% to 7% in healthy subjects and from 8% to 13% in hospitalized patients. Nevertheless, cryofibrinogenemia, when a cryopathy is clinically suspected, has been reported in 12% to 51% of patients. Skin manifestations are usually the first signs and are usually moderate; in addition, cold intolerance, Raynaud phenomenon, purpura, or livedo reticularis often occurs. Skin necrosis, acral ulcers, and gangrene can lead to surgery and amputation. Systemic manifestations are common, and arterial or venous thrombotic events are frequent. Cryofibrinogenemia may be primary (essential) or secondary to other underlying disorders, such as carcinoma, infection, vasculitis, collagen disease, or associated with cryoglobulinemia. The histological features of cryofibrinogenemia can confirm the presence of cryofibrinogen within small and medium arteries, plus occlusive thrombotic diathesis composed of eosinophilic refractile deposits within vessel lumina. Cryofibrinogenemia is a treatable and potentially reversible disease.In moderate forms, it can be treated by simply avoiding cold temperatures. The use of corticosteroids in association with low-dose aspirin is the treatment of choice for moderate forms, although stanozolol is an alternative maintenance therapy. Immunosuppressive therapies, plasmapheresis, and/or intravenous fibrinolysis are useful at treating severe forms of cryofibrinogenemia. The use of anticoagulants is limited to the management of thrombotic events. Treatment of secondary cryofibrinogenemia involves the management of associated diseases. Regular follow-ups are needed because of the high risk of recurrence. Moreover, up to half of patients with cryofibrinogenemia considered as essential may develop lymphomas in the following years. Compared with cryoglobulinemia, less is known about cryofibrinogenemia. Its diagnosis should be considered when suggestive clinical manifestations are present and when there are specific biopsy findings. Although identification of cryofibrinogen in blood samples is simple and inexpensive, cryofibrinogenemia can be asymptomatic, and a lack of diagnosis criteria can make diagnosis difficult to confirm. This review describes the clinical manifestations and the biological and pathological features and discusses the criteria used to diagnose and manage cryofibrinogenemia.
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