ABSTRACT
Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and 126 patients with GN group. Forty-seven CVDEs were observed during the 4.2-years follow up; all 28 patients in the FMF-amyloidosis group and 14/19 patients with GN developed CVDEs before the age of 40 (p = 0.002). CVD mortality was 2.8 times higher (95% CI 1.02-7.76) in patients with FMF-amyloidosis. Across both groups, FMD and FGF23 (p < 0.001) levels were independently associated with the risk of CVDEs. Patients with FMF-amyloidosis are at increased risk of early CVDEs with premature mortality age. FGF 23, FMD and hsCRP can stratify the risk of early CVD in patients with FMF-related AA amyloidosis.
Subject(s)
Amyloidosis/complications , Cardiovascular Diseases/complications , Familial Mediterranean Fever/complications , Kidney Diseases/complications , Adult , Female , Fibroblast Growth Factor-23 , Humans , Male , Middle Aged , Risk Assessment , Young AdultSubject(s)
Arthritis, Juvenile/complications , Arthritis, Juvenile/diagnostic imaging , Osteochondritis Dissecans/diagnostic imaging , Osteochondritis Dissecans/etiology , Adolescent , Arthritis, Juvenile/drug therapy , Child , Child, Preschool , Female , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Humans , Infant , Injections, Intra-Articular , Knee Joint/pathology , Magnetic Resonance Imaging , Male , RadiographyABSTRACT
Clinical Scenario: History of acute ankle sprains can result in chronic ankle instability (CAI). Arthrokinematic changes resulting from CAI may restrict range of motion and contribute to postural control deficits. Mulligan or fibular reposition taping (FRT) has been suggested as a means to realign fibular positional faults and may be an effective way to improve postural control and balance in patients with CAI. Clinical Question: Is there evidence to suggest that FRT will improve postural control for patients with CAI in the affected limb compared with no taping? Summary of Key Findings: Three of the 4 included studies found no significant difference in postural control in patients receiving FRT compared with sham or no tape. Clinical Bottom Line: There is moderate evidence refuting the use of FRT to improve postural control in patients with CAI. Strength of Recommendation: There is grade B evidence to support that FRT does not improve postural control in people with CAI.
Subject(s)
Ankle Joint/physiopathology , Athletic Tape , Joint Instability/therapy , Posture , Biomechanical Phenomena , Chronic Disease , Fibula , HumansABSTRACT
ELMO2 belongs to a family of scaffold proteins involved in phagocytosis and cell motility. ELMO2 can simultaneously bind integrin-linked kinase (ILK) and RhoG, forming tripartite ERI complexes. These complexes are involved in promoting ß1 integrin-dependent directional migration in undifferentiated epidermal keratinocytes. ELMO2 and ILK have also separately been implicated in microtubule regulation at integrin-containing focal adhesions. During differentiation, epidermal keratinocytes cease to express integrins, but ERI complexes persist. Here we show an integrin-independent role of ERI complexes in modulation of microtubule dynamics in differentiated keratinocytes. Depletion of ERI complexes by inactivating the Ilk gene in these cells reduces microtubule growth and increases the frequency of catastrophe. Reciprocally, exogenous expression of ELMO2 or RhoG stabilizes microtubules, but only if ILK is also present. Mechanistically, activation of Rac1 downstream from ERI complexes mediates their effects on microtubule stability. In this pathway, Rac1 serves as a hub to modulate microtubule dynamics through two different routes: 1) phosphorylation and inactivation of the microtubule-destabilizing protein stathmin and 2) phosphorylation and inactivation of GSK-3ß, which leads to the activation of CRMP2, promoting microtubule growth. At the cellular level, the absence of ERI species impairs Ca(2+)-mediated formation of adherens junctions, critical to maintaining mechanical integrity in the epidermis. Our findings support a key role for ERI species in integrin-independent stabilization of the microtubule network in differentiated keratinocytes.
