Bevacizumab dosing every 2 weeks for neovascular age-related macular degeneration refractory to monthly dosing

Purpose:

To evaluate intravitreal bevacizumab every 2 weeks (biweekly) in refractory neovascular age-related macular degeneration (nAMD).

Study design:

Retrospective study.

Methods:

A retrospective study of consecutive nAMD patients unresponsive to monthly intravitreal anti-vascular endothelial growth factor (VEGF) switched to 3–4 biweekly injections.

Results:

Twenty-seven eyes of patients aged 82.08 ?± 6.85 years were included. Prior to the 2-week interval bevacizumab injections, 74.1% (n=20) were treated with both bevacizumab and ranibizumab, 11.1% (3 eyes) also received aflibercept and 14.8% (4 eyes) had received prior treatment of monthly bevacizumab (average number of injections 21.5 ± 6.7). Best corrected visual acuity (BCVA) remained stable between baseline (logMAR 0.72± 0.60) and follow-up (0.76± 0.66) (p=0.41). Mean central macular thickness and macular volume did not change significantly between baseline and follow-up (p=0.35 and p=0.60, respectively). Six eyes (22.2%) showed morphologic anatomic improvements, while 19 eyes (70.4%) were stable and two eyes (7.4%) deteriorated from baseline. Subretinal fluid completely resolved in 3 of the eyes and improved in the other 3 eyes and in this group (22.2%) both central macular thickness (326.2 ± 101.4 versus 297.5 ± 97.2, p=0.002) and macular volume (8.69 ± 1.69 versus 8.22 ± 1.43, p=0.03) were significantly reduced. No adverse events were observed in any of the treated eyes.

Conclusion:

This study demonstrates that biweekly bevacizumab injections are effective in nearly one-quarter of nAMD non-responders with no adverse events reported. Switching earlier, rather than later, to this low cost modality may be of benefit for a portion of non-responders to conventional treatment.

     

Assessment of patency capsule retention using MR diffusion-weighted imaging

Objectives

Evaluate the ability of MR diffusion-weighted imaging (DWI) to predict patency capsule retention in Crohn’s disease (CD).

Methods

Clinical and imaging data were prospectively reviewed for 80 CD patients following patency capsule administration and MR-DWI under institutional review board (IRB) approval with informed consent. Two radiologists separately assessed the presence/absence of restricted diffusion in the distal ileum. Apparent diffusion coefficients (ADC) from three regions of interest on the ileal wall were averaged. The association between restricted diffusion and retention, and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. Ability of ADC to predict retention was assessed with receiver operating characteristic (ROC) curve analysis.

Results

Restricted diffusion in the distal ileum was associated with capsule retention (p?=?0.001, p?<?0.0001). Sensitivity, specificity, PPV and NPV of restricted diffusion for capsule retention were 100.0%, 46.2%, 30.0%, 100% and 100.0%, 56.9%, 34.9%, 100%, respectively, for two radiologists. Accuracy of ADC to predict retention was high (area under the curve?=?0.851, p?<?0.0001). An ADC of 1.47 mm²/s showed 90.0% sensitivity and 50.0% specificity for retention.

Conclusions

Sensitivity and NPV of restricted diffusion for patency capsule retention were 100%, suggesting that DWI may predict gastrointestinal tract capability to pass video camera endoscopy.

Key Points

? Capsule endoscopy enables assessment of the gastrointestinal mucosa in Crohn’s disease ? Prior patency capsule administration is recommended to evaluate gastrointestinal tract patency ? MR diffusion-weighted imaging may detect pathological constriction of the ileum ? Restricted diffusion in the distal ileum was associated with capsule retention ? MR-DWI may predict gastrointestinal tract capability to pass capsule endoscopy

     

Brain network dynamics in the human articulatory loop

Objective

The articulatory loop is a fundamental component of language function, involved in the short-term buffer of auditory information followed by its vocal reproduction. We characterized the network dynamics of the human articulatory loop, using invasive recording and stimulation.

Effects of D-003 on Lipopolysaccharides-induced Osteonecrosis in Rabbits

D-003, a mixture of high molecular weight acids, inhibits cholesterol synthesis prior to mevalonate and prevents osteoporosis induced by ovariectomy in rats, and both osteoporosis and osteonecrosis induced by corticoids in rats. The aim of this study was to investigate effects of D-003 on lipopolysaccharides-induced osteonecrosis in rabbits. Animals were randomized into 5 groups: a sham and four groups injected with lipopolysaccharides: one treated orally with vehicle and three with D-003 (5, 25 and 200 mg/kg, respectively) during four weeks. We assessed the effects of treatments on the incidence of osteonecrosis (number of animals with osteonecrosis lesions/animals per group), the mean numbers and areas of osteonecrosis per animal and on the mean sizes of the bone marrow fat cells. The incidence of osteonecrosis in the groups of D-003 25 and 200 mg/kg was significantly lower than in the positive controls. The reduction of osteonecrosis increased with the doses, but significant dose-dependence relationship was not achieved. D-003 significantly and dose-dependently decreased the number of osteonecrosis lesions per animal as compared to the positive controls. Likewise, the mean osteonecrosis areas in the proximal femoral and humeral bones were significantly decreased by D-003. The injection of lipopolysaccharides significantly increased the average size of bone marrow fat cells as compared to the negative controls, and such increase was significantly and markedly reduced with D-003. It is concluded that D-003 reduced the incidence, number and percent areas of osteonecrosis lesions, and the size of bone marrow fat cells, a marker of adipogenesis, in rabbits with lipopolysaccharides-induced ostenonecrosis.     

Evaluating the effective shear modulus of the cytoplasm in cultured myoblasts subjected to compression using an inverse finite element method

In the present study, we employ our recently developed confocal microscopy-based cell-specific finite element (FE) modeling method, which is suitable for large deformation analyses, to conduct inverse FE analyses aimed at determining the shear modulus of the cytoplasm of cultured skeletal myoblasts, G_cp, and its variation across a number of cells. We calibrate these cell-specific models against experimental data describing the force–deformation behavior of the same cell type, which were published by Peeters et al. (2005b) [J. Biomech.]. The G_cp calculated for five different myoblasts were contained in the range of 0.8–2.4 kPa, with the median value being 1 kPa, the mean being 1.4 kPa, and the standard deviation being 0.7 kPa. The normalized sum of squared errors resulting from the fit between experimental and calculated force–deformation curves ranged between 0.12–0.73%, and Pearson correlations for all fits were greater than 0.99. Determining the mechanical properties of the cytoplasm through cell-specific FE will now allow calculation of cell stresses using cell-specific FE under various cell loading configurations, in support of experimental work in cellular mechanics.