Comparison of silicon oil removal with various viscosities after complex retinal detachment surgery

BACKGROUND: Despite the progress in vitreoretinal surgery and the importance of silicone oil as an adjunct for the treatment of complex forms of retinal detachment, controversy still surrounds the issue of selecting the proper oil viscosity for clinical use. Herein, we evaluate the outcomes of retinal detachment (RD) surgery after removing silicone oils of different viscosities. METHODS: In this retropsective cohort study, eighty-two eyes with surgically re-attached retinas, of which 53 were filled with 5000cs silicone oil and 29 with 1000cs silicone oil were enrolled. We evaluated the outcomes and complications following silicone oil removal. Final anatomic success (stable re-attachment), final visual acuity (VA) and intraocular pressure (IOP)were recorded and analysed. RESULTS: Of 82 eyes, 41 had proliferative vitreoretinopathy (PVR), 24 were associated with intraocular foreign bodies, 10 had endophthalmitis and 7 had proliferative diabetic retinopathy with tractional retinal detachment. Prior to silicone oil removal, the retina was attached in all eyes, 29% had VA ≥ 6/120 and 52% had IOP ≥ 21 mmHg. After silicone oil removal, the retina remained attached in 59(72%) of the eyes, 34% had VA ≥ 6/120 and 9% had IOP ≥ 21 mmHg. Comparing 1000cs and 5000cs silicone oil filled eyes, redetachment occurred more frequently in the latter group especially in cases with associated PVR. Final VA worse than 6/120 was associated with initial VA < 6/120 (OR = 32.2 95%CI 7.4–140.2) and use of 5000cs silicone oil (OR = 7.9 95%CI 1.9–32.2). No factor was significantly associated with final IOP ≥ 21 mmHg. CONCLUSION: In complicated retinal detachment surgery, use of 5000cs silicone oil may be associated with a poorer anatomic and visual outcome compared with 1000cs silicone oil. However there was no difference between the two viscosities in IOP elevation. A randomized controlled study is necessary to further evaluate such a possibility

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis

Subjective and physiological responses among racemic-methadone maintenance patients in relation to relative (S)- vs. (R)-methadone exposure

The definitive version is available at www.blackwell-synergy.comAIMS: To investigate the possibility that (S)-methadone influences therapeutic and adverse responses to rac-methadone maintenance treatment, by examining how subjective and physiological responses among rac-methadone maintenance patients vary in relation to relative exposure to (S)- vs. (R)-methadone. METHODS: Mood states (Profile of Mood States), opioid withdrawal (Methadone Symptoms Checklist), physiological responses (pupil diameter, heart rate, respiration rate, blood pressure), and plasma concentrations (CP) of (R)- and (S)-methadone were measured concurrently 11–12 times over a 24-h interdosing interval in 55 methadone maintenance patients. Average steady-state plasma concentrations (Cav) and pharmacodynamic responses were calculated using area under the curve (AUC). Linear regression was used to determine whether variability in pharmacodynamic responses was accounted for by (S)-methadone Cav controlling for (R)-methadone Cav and rac-methadone dose. Ratios of (S)-:(R)-methadone using AUCCP and trough values were correlated with pharmacodynamic responses for all subjects and separately for those with daily rac-methadone doses ≥ 100 mg. RESULTS: (S)-methadone Cav accounted for significant variability in pharmacodynamic responses beyond that accounted for by (R)-methadone Cav and rac-methadone dose, showing positive associations (partial r) with the intensity of negative mood states such as Tension (0.28), Fatigue (0.31), Confusion (0.32), and opioid withdrawal scores (0.30); an opposite pattern of relationships was evident for (R)-methadone. The plasma (S)-:(R)-methadone AUCCP ratio (mean ± SD 1.05 ± 0.21, range 0.65–1.51) was not significantly related to pharmacodynamic responses for the subjects as a whole but showed significant positive associations (r) with the intensity of negative mood states such as Total Mood Disturbance (0.61), Tension (0.69), Fatigue (0.65), Confusion (0.64), Depression (0.49) and heart rate (0.59) for the ≥ 100-mg dose range. CONCLUSIONS: These findings agree with previous evidence that (S)-methadone is associated with a significant and potentially adverse profile of responses distinct from that of (R)-methadone. Individual variability in relative (S)- vs. (R)-methadone exposure may be associated with variability in response to rac-methadone maintenance treatment.Timothy B. Mitchell, Kyle R. Dyer, David Newcombe, Amy Salter, Andrew A. Somogyi, Felix Bochner and Jason M. Whit