470 research outputs found
FRI0499 ACROMEGALY ARTROPATHY: IS THERE SOMETHING MORE BEHIND THE PAIN? A CROSS-SECTIONAL STUDY TO EVALUATE RHEUMATIC DISEASE IN GROWTH HORMONE SECRETING TUMOR PATIENTS
Background:Acromegaly is a rare disease with a remarkable impact on patients, both in terms of life expectancy and quality of life. Osteo-articular complications are one of the most frequently reported bothers. The "acromegaly artropathy" characterizes more than 70% of patients at diagnosis. Artropathy affects both spine and peripheral joints. A recent prospective study documented progression of acromegalic arthropathy identified as a worsening of osteophytes and joint space narrowing in 72–74% of patients despite long-term biochemical control. In addiction the Literature has occasionally reported cases of simultaneous presence of rheumatic diseases (rheumatoid arthritis, polymyalgia rheumatica, undifferentiated connective tissue diseases) and acromegaly and in all these cases the treatment has been delayed, because of wrong symptoms attribution to acromegaly artropathy.Objectives:The primary goal of the study is to better characterize joint pain in acromegaly patients and to evaluate the prevalence of rheumatic disease in growth hormone (GH) secreting pituitary tumor patients.Methods:We enrolled 20 acromegaly subjects (AS) and 20 control subjects (CS). In each subject immunological pattern (rheumatoid factor – RF; antinuclear antibodies - ANA, ENA; anti-citrullinated protein antibodies - ACPA; erythrocyte sedimentation rate – ESR) has been evaluated; they, also, underwent bilateral joint ultrasound of hands and wrists and nail capillaroscopy. The Chi square test and the Fisher's exact test were used to evaluate the association between binary variables, while the Spearman's test to evaluate the correlation of continuous ones. A multiple or logistic regression model was calculated in order to define the association between the capillaroscopic alterations and other detected variables.Results:Articular pain emerged as significantly more frequent in AS (p = 0.0269). No statistically significant differences are detected regarding immunological pattern. ANA and ENA screening resulted positive in 10% in AS and in 5% in CS. No IgA ACPA were detected in AS or CS, while IgG ACPA were positive only in one AS subject. No significant differences were detected between IgM and IgG RFin the two groups (AS 5% and CS 0%). Three fold higher IgG FR in AS compared to CS were detected. ESR levels were significantly higher than CS (p = 0.0405), as well as increased power doppler (PWD) articular uptake (AS 30% vs CS 5% p 0.081). The capillaroscopic evaluation showed a significant difference in almost each parameter that has been evaluated (logistic regression: number of enlargement p 0.004, hemorragies p 0.01 and capillaries p 0.001), showing a moderate-severe microangiopathy in AS. Interestingly, analyzing only the acromegaly cohort, we noticed higher GH levels at the enrollment in patients which developed capillary enlargements (GH: 0.95 ng/ml IQ 0,6-1,6) compared to other ones (GH: 0.55 ng/ml IQ 0.4-0.7; p = 0.08) and a significant lower number of hemorrhages (p = 0.02) in patients treated with GH antagonist pegvisomant.Conclusion:Our results demonstrated that joint damage in acromegaly does not seem to have an autoimmune etiology. Therefore, articular damage is mechanical and increased ESR and PWD alterations seems to confirm the presence of an inflammatory component. In addition, acromegaly is characterized by a microvascular pattern of moderate-severe microangiopathy, without correlation to IGF-I, but GH levels. Although requiring further confirmatory studies, our preliminary results seem to indicate how the capillaroscopic examination could be useful to detect earlier microangiopathy and to identify patients with a greater risk of macroangiopathy development..References:[1]Claessen KMJA et al. Bone and joint disorders in acromegaly. Neuroendocrinology. 2016;103(1):86-95.[2]Örük G et al. Is every joint symptom related to acromegaly? Endocrine. 2013 Apr;43(2):404-11.Disclosure of Interests:None declare
On the Mechanism of Time--Delayed Feedback Control
The Pyragas method for controlling chaos is investigated in detail from the
experimental as well as theoretical point of view. We show by an analytical
stability analysis that the revolution around an unstable periodic orbit
governs the success of the control scheme. Our predictions concerning the
transient behaviour of the control signal are confirmed by numerical
simulations and an electronic circuit experiment.Comment: 4 pages, REVTeX, 4 eps-figures included Phys. Rev. Lett., in press
also available at
http://athene.fkp.physik.th-darmstadt.de/public/wolfram.htm
POS0090 RISK OF QT INTERVAL PROLONGATION ASSOCIATED WITH CHRONIC USE OF HYDROXYCHLOROQUINE IN RHEUMATIC PATIENTS AND THE EFFECT OF COTREATMENTS
Background:Hydroxychloroquine (HCQ) has been used safely for over 60 years in rheumatic patients. However, following its recent use in covid-19 disease, its safety has been questioned, following controversial reports of cardiac toxicity1, possibly related to a prolongation of the QT interval2.Objectives:To explore the influence of chronic treatment with hydroxychloroquine on QT interval in rheumatic patients, and the possible effects of drug-to-drug interference3.Methods:12-lead electrocardiogram tracings were recorded with standard equipment in 229 ambulatory patients (SLE = 53, RA = 52, SSc = 56, UCTD = 38, Others = 30). The present analysis was performed on corrected QT intervals (QTc) calculated according to Framingham formula (QTc = QT+0.154 (1−RR)), with ULN = 449 ms in males, and 467 ms in females. Estimated glomerular filtrate rate (eGFR) was calculated from serum creatinine with the CKD-EPI equation. The influence on QTc values of demographic variables, chronic (≥3 months) HCQ treatment, and of the use of selected comedications -Statins, Angiotensin Converting Enzyme inhibitors (ACEi), Angiotensin Receptor Blockers (ARBs), Selective Serotonin Reuptake Inhibitors (SSRIs), Proton-Pump Inhibitors (PPI), Calcium Channel Blockers (CCBs) – were evaluated by parametric or non parametric statistical methods, as appropriate. All statistic al analyses were performed with the IBM SPSS statistical package version 25.Results:Table 1.Demographic and clinical variables in patients treated with HCQ (HCQ+) and in controls (HCQ-).NAgeYrs±SDFemaleN%eGFRmL/min/1.73m2StatinsN%ACEiN%ARBN%SSRIN%PPIN%CCBN%All22958.02±14.3620690.087.1418.962912.74821.8198.3146.113860.33013.1HCQ+13258.71±14.4912292.487.0020.041813.63224.2118.396.88060.61712.9HCQ-9757.51±14.308486.687.3217.471111.31616.588.255.25859.81313.4p0.5320.1830.8970.6900.1891.0000.7821.0001.000Demographic variables, and the use of evaluated comedications were not different in HCQ+ and HCQ- patients (Table 1). In the whole population, the QTc mean duration was 416.72 ± 20.70 ms, and was correlated with age (r = 0.215, p= 0.001), but not with gender (p = 0.548), eGFR (r = -0.93, p = 0.163), or disease (p = 0.092). In only 4 patients (HCQ+: 3 (2.3%) – HCQ-: 1 (1%), p = 0.639) QTc duration was above ULN.QTc duration was not associated with the use of Statins, ACEi, ARBs, or SSRIs (p = 0.454, 0.276, 0.475, and 0.131 respectively), but was significantly prolonged in patients treated with HCQ (421.26 ± 19.19 vs 410.55 ± 21.18 msec, p < 0.001), PPIs (420.57 ± 21.45 vs 410.89 ± 18.12 ms, p < 0.001), and CCBs (424.22 ± 25.97 vs 415.59 ± 19.62 ms, p < 0.033). Furthermore, as reported in Fig. 1, our data show a trend - albeit not statistically significant - towards an additive effect on QT prolongation of the association of PPIs and CCBs with HCQ, even more evident in the case of association of the 3 drug classes.Conclusion:In this study, the QTc interval was significantly prolonged in patients treated with hydroxychloroquine as compared to controls, although significant prolongation was extremely infrequent. Furthermore, our data revealed signs of drug-drug interference, suggesting that regular monitoring of the electrocardiogram is advisable in these patients, often undergoing cotreatment with multiple drugs.References:[1]Imad M. Tleyjeh, et al. The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis. Mayo Clin Proc Innov Qual Outcomes. 2020 Nov 2 doi: 10.1016/j.mayocpiqo.2020.10.005 [Epub ahead of print].[2]Teodoro J. Oscanoa, et al. Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis. Int J Antimicrob Agents.[3]Byung Jin Choi, et al. Risk of QT prolongation through Drug-drug Interactions between Hydroxychloroquine and Concomitant Drugs Prescribed in Real-world Practice. Preprint from Research Square, 22 Sep 2020 DOI: 10.21203/rs.3.rs-79572/v1 PPR: PPR217328.Disclosure of Interests:None declare
Controlling spatiotemporal chaos in oscillatory reaction-diffusion systems by time-delay autosynchronization
Diffusion-induced turbulence in spatially extended oscillatory media near a
supercritical Hopf bifurcation can be controlled by applying global time-delay
autosynchronization. We consider the complex Ginzburg-Landau equation in the
Benjamin-Feir unstable regime and analytically investigate the stability of
uniform oscillations depending on the feedback parameters. We show that a
noninvasive stabilization of uniform oscillations is not possible in this type
of systems. The synchronization diagram in the plane spanned by the feedback
parameters is derived. Numerical simulations confirm the analytical results and
give additional information on the spatiotemporal dynamics of the system close
to complete synchronization.Comment: 19 pages, 10 figures submitted to Physica
Phase II study of the safety and efficacy of oral capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma
n/
Bursts in the Chaotic Trajectory Lifetimes Preceding the Controlled Periodic Motion
The average lifetime () it takes for a randomly started trajectory
to land in a small region () on a chaotic attractor is studied. is
an important issue for controlling chaos. We point out that if the region
is visited by a short periodic orbit, the lifetime strongly deviates
from the inverse of the naturally invariant measure contained within that
region (). We introduce the formula that relates
to the expanding eigenvalue of the short periodic orbit
visiting .Comment: Accepted for publication in Phys. Rev. E, 3 PS figure
Intermittency transitions to strange nonchaotic attractors in a quasiperiodically driven Duffing oscillator
Different mechanisms for the creation of strange nonchaotic attractors (SNAs)
are studied in a two-frequency parametrically driven Duffing oscillator. We
focus on intermittency transitions in particular, and show that SNAs in this
system are created through quasiperiodic saddle-node bifurcations (Type-I
intermittency) as well as through a quasiperiodic subharmonic bifurcation
(Type-III intermittency). The intermittent attractors are characterized via a
number of Lyapunov measures including the behavior of the largest nontrivial
Lyapunov exponent and its variance as well as through distributions of
finite-time Lyapunov exponents. These attractors are ubiquitous in
quasiperiodically driven systems; the regions of occurrence of various SNAs are
identified in a phase diagram of the Duffing system.Comment: 24 pages, RevTeX 4, 12 EPS figure
Quasiperiodic time dependent current in driven superlattices: distorted Poincare maps and strange attractors
Intriguing routes to chaos have been experimentally observed in semiconductor
superlattices driven by an ac field. In this work, a theoretical model of time
dependent transport in ac driven superlattices is numerically solved. In
agreement with experiments, distorted Poincare maps in the quasiperiodic regime
are found. They indicate the appearance of very complex attractors and routes
to chaos as the amplitude of the AC signal increases. Distorted maps are caused
by the discrete well-to-well jump motion of a domain wall during spiky
high-frequency self-sustained oscillations of the current.Comment: 10 pages, 4 figure
Treatment of Acute Myeloid Leukemia with 20-30% Bone Marrow Blasts
The transition of patients with ≥20% <30% bone marrow (BM) blast from the FAB category of myelodysplasia to the family of acute myeloid leukemia (AML) according to the recent WHO classification has not resolved the argument as to whether the natural history and responsiveness to therapy of these diseases is comparable to that of AML with > 30% BM blast. These controversies are even more manifest when it comes to elderly patients in whom concern for intensive chemotherapy (IC) related toxicity is the critical determinant for the therapeutic choice. In fact, due to concerns of treatment-related morbidity and mortality associated with delivery of IC, approximately only 30% of all patients ≥65 years are considered eligible for this approach. Therefore, a great deal of attention has been dedicated to alternative agents such as hypomethylators (azacitidine and decitabine). Actually, these agents have shown efficacy with reduced toxicity when administered to elderly patients with 20–30% BM blasts and not eligible for IC. In the present review, we will discuss the clinical results achieved in the treatment of elderly patients with 20%–30% BM blasts AML using intensive chemotherapy (IC) or hypomethylating agents. Overall, our survey of the literature suggests that only controlled, randomized, clinical trials will answer the question as to whether hypomethylating agents has the potential to substitute for IC even in elderly patients with an optimal functional status
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