Evaluation of choroidal and retinal thickness measurements in adult hemodialysis patients using spectral-domain optical coherence tomography

Purpose: To assess the effect of hemodialysis on retinal and choroidal thicknesses using spectral-domain optical coherence tomography (SD-OCT). Methods: In this prospective interventional study, 25 hemodialysis patients (17 male, 8 female) were enrolled. All participants underwent high-speed, high-resolution SD-OCT (lambda=840 mm; 26.000 A-scans/s; 5 mu m resolution) before and after hemodialysis. Choroidal thickness was measured perpendicularly from the outer edge of the retinal pigment epithelium to the choroid-sclera boundary at the fovea and at five additional points: 500 mu m and 1000 mu m nasal to the fovea and 500 mu m, 1000 mu m, and 1500 mu m temporal to the fovea. Two masked physicians performed the measurements. Choroidal and retinal thicknesses before and after hemodialysis were compared. Results: The median choroidal thicknesses before and after hemodialysis were 182 mu m (range, 103-374 mu m) and 161 mu m (range, 90-353 mu m), respectively (P0.05). Systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, heart rate, and ocular perfusion pressure significantly decreased after hemodialysis (P<0.001). Intraocular pressure did not vary significantly (P=0.540). Conclusion: Hemodialysis seems to cause a significant decrease in choroidal thickness, whereas it has no effect on retinal thickness. This significant decrease in choroidal thickness might be due to the extensive fluid absorption in hemodialysis, which could result in decreased ocular blood flow

Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis

WOS: 000338636500018PubMed ID: 24252034Objectives. To investigate the relationship between enthesitis and disease activity, functional status, fatigue, joint mobility, radiological damage, laboratory parameter and quality of life in patients with ankylosing spondylitis (AS). Methods. A total of 421 patients with AS (323 male and 98 female) who were included in the Turkish League Against Rheumatism Registry were enrolled in the study. The Bath AS Disease Activity Index (BASDAI), fatigue, the Bath AS Functional Index (BASFI), the Bath AS Metrology Index (BASMI), the Maastricht AS Enthesitis Score (MASES), AS quality of life (ASQoL), the Bath AS Radiology Index (BASRI) and erythrocyte sedimentation rate (ESR) were evaluated. Results. Enthesitis was detected in 27.3% of patients. There were positive correlations between MASES and BASDAI, BASFI and fatigue (p < 0.05). MASES was not correlated with BASRI, BASMI, ASQoL and ESR. The mean MASES score was 1.1 +/- 2.4. The most frequent regions of enthesopathies were right iliac crest, spinous process of L5 and proximal to the insertion of left achilles tendon, respectively. Conclusions. Enthesitis was found to be associated with higher disease activity, higher fatigue, worse functional status and lower disease duration. As enthesitis was correlated with BASDAI, we conclude that enthesitis can reflect the disease activity in patients with AS.Pfizer CompanyThe authors express their gratitude to all members of the TRASD-IP AS Study group for their cooperation and to Pfizer Company for the registry sponsorship

Risdiplam in Type 1 Spinal Muscular Atrophy

BackgroundType 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein.MethodsWe report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds.ResultsA total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study.ConclusionsIn infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.)The small molecule risdiplam increased the expression of SMN protein in blood in 21 infants with type 1 spinal muscular atrophy. Post hoc clinical features of sitting ability and respiratory status were reported

Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls

Background Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. Methods We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. Results A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P&lt;0.001 for all comparisons). The most common serious adverse events were pneumonia, bronchiolitis, hypotonia, and respiratory failure. Conclusions In this study involving infants with type 1 SMA, risdiplam resulted in higher percentages of infants who met motor milestones and who showed improvements in motor function than the percentages observed in historical cohorts. Longer and larger trials are required to determine the long-term safety and efficacy of risdiplam in infants with type 1 SMA. (Funded by F. Hoffmann-La Roche; FIREFISH ClinicalTrials.gov number, .)Small-Molecule SMN2 Modifier in Type 1 SMA The pre-mRNA SMN2 splicing modifier risdiplam was administered orally to 41 infants with type 1 spinal muscular atrophy. After 12 months of treatment, 12 infants were able to sit without support, and most had better scores on motor-performance scales than the upper limit of confidence intervals from historical controls