Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus

Background: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. Methods: The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. Results: A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/-standard deviation) by 0.35 +/- 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/- 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Conclusions: Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not

Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis : results from the PREVENT-JIA trial

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVES: To investigate the ability of high-sensitivity C-reactive protein (hsCRP) and S100A12 to serve as predictive biomarkers of successful drug withdrawal in children with clinical remission of juvenile idiopathic arthritis (JIA). METHODS: This multicentre trial (PREVENT-JIA) enrolled 119 patients with JIA in clinical remission, and 100 patients reached the intervention phase in which the decision whether to continue or stop treatment was based on S100A12 and hsCRP levels. Patients were monitored for 12 months after stopping medication for flares of disease. Results were compared with withdrawal of therapy without biomarker-based stratification in patients from the German Biologika in der Kinderrheumatologie (BiKeR) pharmacovigilance registry. RESULTS: In the PREVENT-JIA group, 49 patients had a flare, and 45% of patients stopping medication showed flares within the following 12 months. All patients (n=8) continuing therapy due to permanently elevated S100A12/hsCRP at more than one visit flared during the observation phase. In the BiKeR control group, the total flare rate was 62%, with 60% flaring after stopping medication. The primary outcome, time from therapy withdrawal to first flare (cumulative flare rate after therapy withdrawal), showed a significant difference in favour of the PREVENT-JIA group (p=0.046; HR 0.62, 95% CI 0.38 to 0.99). As additional finding, patients in the PREVENT-JIA trial stopped therapy significantly earlier. CONCLUSION: Biomarker-guided strategies of therapy withdrawal are feasible in clinical practice. This study demonstrates that using predictive markers of subclinical inflammation is a promising tool in the decision-making process of therapy withdrawal, which translates into direct benefit for patients. TRIAL REGISTRATION NUMBER: ISRCTN69963079.publishersversionPeer reviewe

Thermodynamic and diamagnetic properties of weakly doped antiferromagnets

Finite-temperature properties of weakly doped antiferromagnets as modeled by the two-dimensional t-J model and relevant to underdoped cuprates are investigated by numerical studies of small model systems at low doping. Two numerical methods are used: the worldline quantum Monte Carlo method with a loop cluster algorithm and the finite-temperature Lanczos method, yielding consistent results. Thermodynamic quantities: specific heat, entropy and spin susceptibility reveal a sizeable perturbation induced by holes introduced into a magnetic insulator, as well as a pronounced temperature dependence. The diamagnetic susceptibility introduced by coupling of the magnetic field to the orbital current reveals an anomalous temperature dependence, changing character from diamagnetic to paramagnetic at intermediate temperatures.Comment: LaTeX, 10 pages, 10 figures, submitted to Phys. Rev.

Differential roles of nitric oxide synthase isozymes in cardiotoxicity and mortality following chronic doxorubicin treatment in mice

The roles of individual nitric oxide synthases (NOS) in anthracycline-related cardiotoxicity are not completely understood. We investigated the effects of a chronic treatment with doxorubicin (DOX) on knockouts of the individual NOS isozymes and on transgenic mice with myocardial overexpression of eNOS. Fractional shortening (FS) was reduced in untreated homozygous nNOS and iNOS knockouts as well as in eNOS transgenics. DOX-induced FS decrease in wild-type mice was attenuated only in eNOS knockouts, which were found to overexpress nNOS. No worsening of contractility was observed in DOX-treated eNOS transgenics and iNOS knockouts. Although the surviving DOX-treated nNOS knockouts exhibited no further impairment in contractility, most (70%) animals died within 7 weeks after treatment onset. In comparison to untreated wild-type hearts, the nitric oxide (NO) level was lower in hearts from DOX-treated wild-type mice and in all three untreated knockouts. DOX treatment had no effect on NO in the knockouts. These data indicate differential roles of the individual NOS in DOX-induced cardiotoxicity. Protection against DOX effects conferred by eNOS deletion may be mediated by a compensatory overexpression of nNOS. NOS inhibition-based prevention of anthracycline-induced cardiotoxicity should be eNOS-selective, simultaneously avoiding inhibiting nNOS

ECCD-induced sawtooth crashes at W7-X

The optimised superconducting stellarator W7-X generates its rotational transform by means of external coils, therefore no toroidal current is necessary for plasma confinement. Electron cyclotron current drive experiments were conducted for strikeline control and safe divertor operation. During current drive experiments periodic and repetitive crashes of the central electron temperature, similar to sawtooth crashes in tokamaks, were detected. Measurements from soft x-ray tomography and electron cyclotron emission show that the crashes are preceded by weak oscillating precursors and a displacement of the plasma core, consistent with a (m, n)=(1, 1) mode. The displacement occurs within 100μs, followed by expulsion and redistribution of the core into the external part of the plasma. Two types of crashes, with different frequencies and amplitudes are detected in the experimental program. For these non-stationary parameters a strong dependence on the toroidal current is found. A 1-D heuristic model for current diffusion is proposed as a first step to explain the characteristic crash time. Initial results show that the modelled current diffusion timescale is consistent with the initial crash frequency and that the toroidal current rise shifts the position where the instability is triggered, resulting in larger crash amplitudes