Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

Aetiology of community-acquired, acute gastroenteritis in hospitalised adults: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The aetiology of severe gastroenteritis leading to hospitalisation in adults frequently remains unclear. Our objective was to study the causes and characteristics of community-acquired, acute gastroenteritis in adult hospitalized patients to support the clinical management of these patients.</p> <p>Methods</p> <p>From August 2005 to August 2007, we conducted a prospective cohort study among patients ≥18 y hospitalized with community-acquired gastroenteritis in a university hospital in Berlin, Germany. Stool specimens were examined for 26 gastrointestinal pathogens, supplemented by serologic tests for antibodies to <it>Campylobacter spp.</it>, <it>Yersinia spp.</it>, and <it>Entamoeba histolytica</it>. Patient data on demographics and clinical presentation were recorded and analyzed. Coexisting medical conditions were assessed using the Charlson Comorbidity Index score.</p> <p>Results</p> <p>Of 132 patients presenting with acute community-acquired gastroenteritis, 104 were included in the study. A non-infectious aetiology was diagnosed in 8 patients (8%). In 79 (82%) of the remaining 96 patients at least one microorganism was identified. <it>Campylobacter spp. </it>(35%) was detected most frequently, followed by norovirus (23%), <it>Salmonella spp. </it>(20%), and rotavirus (15%). In 46% of the patients with <it>Campylobacter spp. </it>infection, the diagnosis was made solely by serology. More than one pathogen was found in seventeen (22%) patients. Simultaneous infection was significantly more likely in patients with rotavirus and salmonella infections (RR 3.6; 95% CI: 1.8–7.4; RR 2.5; 95%CI: 1.2–5.5). Length of hospital stay (median: 5.5 days) was independent of the pathogen, but was associated with coexisting medical conditions (OR 4,8; 95%CI:2,0–11,6).</p> <p>Conclusion</p> <p>Known enteric pathogens were detected in 82% of adult patients who were hospitalized with acute gastroenteritis. We found that currently used culture-based methods may miss a substantial proportion of <it>Campylobacter </it>infections, and additional serological testing for <it>Campylobacter </it>should be considered. Viral infections emerged as an important cause of severe gastroenteritis in adults, and viral-bacterial co-infections in adults are probably underrecognized so far. The presence of coexisting medical conditions – but not the etiological agent – was a predictor for the duration of the hospital stay.</p

Functionally Relevant Maculopathy and Optic Atrophy in Spinocerebellar Ataxia Type 1

Background: Spinocerebellar ataxia type 1 (SCA-ATXN1) is an inherited progressive ataxia disorder characterized by an adult-onset cerebellar syndrome combined with nonataxia signs. Retinal or optic nerve affection are not systematically described. Objectives: To describe a retinal phenotype and its functional relevance in SCA-ATXN1. Methods: We applied optical coherence tomography (OCT) in 20 index cases with SCA-ATXN1 and 22 healthy controls (HCs), investigating qualitative changes and quantifying the peripapillary retinal nerve fiber layer (pRNFL) thickness and combined ganglion cell and inner plexiform layer (GCIP) volume as markers of optic atrophy and outer retinal layers as markers of maculopathy. Visual function was assessed by high- (HC-VA) and low-contrast visual acuity (LC-VA) and the Hardy-Rand-Rittler pseudoisochromatic test for color vision. Results: Five patients (25%) showed distinct maculopathies in the ellipsoid zone (EZ). Furthermore, pRNFL (P < 0.001) and GCIP (P = 0.002) were reduced in patients (pRNFL, 80.86 ± 9.49 μm; GCIP, 1.84 ± 0.16 mm3) compared with HCs (pRNFL, 97.02 ± 8.34 μm; GCIP, 1.98 ± 0.12 mm3). Outer macular layers were similar between groups, but reduced in patients with maculopathies. HC-VA (P = 0.002) and LC-VA (P < 0.001) were reduced in patients (HC-VA [logMAR]: 0.01 ± 010; LC-VA [logMAR]: 0.44 ± 0.16) compared with HCs (HC-VA [logMAR]: –0.12 ± 0.08; LC-VA [logMAR]: 0.25 ± 0.05). Color vision was abnormal in 2 patients with maculopathies. Conclusions: A distinct maculopathy, termed EZ disruption, as well as optic atrophy add to the known nonataxia features in SCA-ATXN1. Whereas optic atrophy may be understood as part of a widespread neurodegeneration, EZ disruption may be explained by effects of ataxin-1 gene or protein on photoreceptors. Our findings extend the spectrum of nonataxia signs in SCA-ATXN1 with potential relevance for diagnosis and monitoring

Evaluating the Impact of Intravitreal Aflibercept on Diabetic Retinopathy Progression in the VIVID-DME and VISTA-DME Studies

Purpose To evaluate the impact of intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Tarrytown, NY) versus laser on progression of diabetic retinopathy (DR) severity in Intravitreal Aflibercept Injection in Vision Impairment due to DME (VIVID-DME) and Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA-DME). Design Secondary and exploratory analyses of 2 phase 3, randomized, controlled studies. Participants All patients with a baseline Diabetic Retinopathy Severity Scale (DRSS) score based on fundus photograph (full analysis), patients who progressed to proliferative DR (PDR) (safety analysis) in VIVID-DME (n = 403) and VISTA-DME (n = 459), or both. Methods We randomized patients with diabetic macular edema (DME) to intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation at baseline and sham injections at every visit. Main Outcome Measures Proportions of patients with 2-step or more and 3-step or more improvements from baseline in DRSS score, who progressed to PDR, and who underwent panretinal photocoagulation (PRP). Results Among patients with an assessable baseline DRSS score, most showed moderately severe or severe nonproliferative DR. The proportions of patients treated with 2q4, 2q8, and laser with a 2-step or more improvement in DRSS score at week 100 were 29.3%, 32.6%, and 8.2%, respectively, in VIVID-DME and 37.0%, 37.1%, and 15.6%, respectively, in VISTA-DME; the proportions with a 3-step or more improvement in DRSS score were 7.3%, 2.3%, and 0%, respectively, and 22.7%, 19.9%, and 5.2%, respectively. Fewer patients in the 2q4 and 2q8 groups versus the laser group progressed to PDR at week 100 in VISTA-DME (1.5% and 2.2% vs. 5.3%) and VIVID-DME (3.2% and 2.0% vs. 12.3%). The proportions of patients who underwent PRP were 2.9%, 0.7%, and 4.5%, respectively, in VIVID-DME and 1.9%, 0.7%, and 5.2%, respectively, in VISTA-DME. The most frequent serious ocular adverse event at week 100 was cataract (pooled intravitreal aflibercept, 1.7% of patients; laser, 3.5% of patients). Conclusions These analyses demonstrate the benefit of intravitreal aflibercept over laser with respect to DR progression, suggesting a benefit on DME, and on underlying DR

The kallikrein–kinin system in diabetic nephropathy

Diabetic nephropathy is the major cause of end-stage renal disease worldwide. Although the renin-angiotensin system has been implicated in the pathogenesis of diabetic nephropathy, angiotensin I-converting enzyme (ACE) inhibitors have a beneficial effect on diabetic nephropathy independently of their effects on blood pressure and plasma angiotensin II levels. This suggests that the kallikrein-kinin system (KKS) is also involved in the disease. To study the role of the KKS in diabetic nephropathy, mice lacking either the bradykinin B1 receptor (B1R) or the bradykinin B2 receptor (B2R) have been commonly used. However, because absence of either receptor causes enhanced expression of the other, it is difficult to determine the precise functions of each receptor. This difficulty has recently been overcome by comparing mice lacking both receptors with mice lacking each receptor. Deletion of both B1R and B2R reduces nitric oxide (NO) production and aggravates renal diabetic phenotypes, relevant to either lack of B1R or B2R, demonstrating that both B1R and B2R exert protective effects on diabetic nephropathy presumably via NO. Here, we review previous epidemiological and experimental studies, and discuss novel insights regarding the therapeutic implications of the importance of the KKS in averting diabetic nephropathy

Load Position Estimation for Crane Anti-Sway Control Systems

A rising number of modern cranes are equipped with anti-sway control systems to facilitate crane operation, improve positioning accuracy, and increase turnover. Commonly, these industrial crane control systems require pendulum state information for feedback control. Therefore, a pendulum sway sensor (e.g., a rope-mounted gyroscope) and a signal processing algorithm are required. Such a signal processing algorithm needs to filter out disturbances from both the sensor and the crane, e.g., signal noise and string oscillations of a long rope. Typically, these signal processing algorithms require the knowledge of the acceleration of the rope suspension point. This acceleration signal is often estimated from drive models. When drive models are uncertain, the pendulum state estimation accuracy suffers from drive model inaccuracy. In this contribution, an improved estimation algorithm is presented which estimates the load position without relying on the rope suspension point acceleration. The developed Extended Kalman Filter is implemented on a Liebherr mobile harbor crane and its effectiveness is validated with multiple test rides and GPS load position reference measurements

Influence of Ranibizumab versus laser photocoagulation on radiation retinopathy (RadiRet) - a prospective randomized controlled trial

Purpose: To demonstrate superiority of intravitreal ranibizumab 0.5 mg compared to focal and peripheral laser treatment in patients with radiation retinopathy for choroidal melanoma. Methods: Inclusion criteria were as follows: patients with radiation retinopathy and visual acuity impairment due to radiation maculopathy accessible for laser therapy, age ≥ 18 years, and BCVA less than 20/32. The main objective was to study the change in best-corrected visual acuity (BCVA) over 6 months from ranibizumab 0.5 mg (experimental) compared to focal laser of the macula and panretinal laser treatment of the ischemic retina (control) in patients with radiation retinopathy in choroidal melanoma. The secondary objectives of the radiation retinopathy study were to compare functional and anatomical results between ranibizumab and laser group over 12 months and to measure the frequency of vitreous hemorrhage and rubeosis iridis. Results: The intention-to-treat analysis included 31 patients assigned to ranibizumab (n = 15) or laser treatment (n = 16). In terms of BCVA at month 6, ranibizumab was superior to laser treatment, with an advantage of 0.14 logMAR, 95% CI 0.01 to 0.25, p = 0.030. The positive effect of ranibizumab disappeared after treatment was discontinued. Similar results without statistically significant difference were found with respect to macular thickness. In both groups, no change was observed at month 6 in the size of ischemia in the macula or periphery compared to baseline. There was 1 case of vitreous hemorrhage in the laser group and no case of rubeosis iridis over time. Conclusions: This study showed a statistically significant improvement in visual acuity and clear superiority of ranibizumab compared to laser treatment up to 26 weeks, but this effect disappeared at week 52 after completion of intravitreal treatment. Ranibizumab and PRP are considered equivalent in terms of the non-appearance of proliferative radiation retinopathy during the study. Trial registration: EudraCT Number: 2011-004463-6

Dose-Response-Relationship between Number of Laser Burns and IOP Reduction in Cyclophotocoagulation: An Animal Study

Purpose. The relationship between number of laser burns of cyclophotocoagulation (CPC) and intraocular pressure (IOP) reduction is unknown. This animal model was established to reveal a possible dose-response-relationship between the number of applied laser burns and the IOP lowering effect. Methods. 30 chinchilla bastard rabbits were divided into 5 groups and treated with either 1, 5, 10, 20, or 30 CPC burns, respectively. IOP was followed up for 1 week. IOP reduction of a single 30-burn treatment was compared with a fractionated treatment (three sessions; one week in between; 10 burns/session). Results. IOP reduction increases nonlinearly with the number of CPC burns (max. -6.1±1.4 mmHg). Fractionated treatment shows similar IOP reduction with less complications and more constant results compared to single session treatment. Conclusions. The study reveals a complex relationship between IOP reduction and the number of CPC burns. Fractionated CPC gives comparable IOP reduction at a higher degree of safety