NEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH ADVANCED VISUAL LOSS TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: Clinical Outcome and Prognostic Indicators.

PURPOSE: To describe visual outcome and prognostic indicators in neovascular age-related macular degeneration with advanced visual loss at the initiation of anti-vascular endothelial growth factor therapy. METHODS: A retrospective chart review was performed on a consecutive series of 1,410 patients with neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor therapy at the Medical College of Wisconsin. Subjects were included if at the initiation of therapy they had 20/200 or worse visual acuity (VA) with no other visually limiting eye disease and a minimum follow-up of 6 months. The change in VA at 6 months and 12 months was assessed compared with baseline. Visual improvement/worsening was defined as at least ± 0.3 logMAR (equivalent to 15 ETDRS [Early Treatment Diabetic Retinopathy Study] letters) change. Other factors for analysis included number of injections received, drug type, and various clinical and imaging findings. RESULTS: One hundred thirty-one cases met the study criteria, and 97 were followed for 12 months. Baseline VA was 1.38 logMAR (20/480 Snellen equivalent). Mean VA change (logMAR) consisted of an improvement of 0.23 (P < 0.0001) at 6 months and 0.17 (P = 0.003) at 12 months. At 12 months, VA improved in 45% and worsened in 20%. Among subjects with baseline VA worse than 20/400, VA improved in 57% and worsened in 20%. On univariate analysis at either the 6 months or 12 months follow-up, visual improvement was associated with retinal hemorrhage (P = 0.03) and subretinal fluid (P = 0.02), whereas visual worsening was associated with retinal pigment epithelial detachment (P = 0.04) and intraretinal fluid (P = 0.01). With multivariate analysis, visual improvement was predicted by both a larger number of injections received (P = 0.001) and a poorer baseline VA (P = 0.001). Injection medication type did not influence outcome. CONCLUSION: Statistically significant visual improvement was observed in association with anti-vascular endothelial growth factor therapy in patients with severe neovascular age-related macular degeneration, even in patients whose initial VA was worse than that studied in large anti-vascular endothelial growth factor clinical trials. Numerous clinically discernable or potentially modifiable factors may influence outcome in such patients.

FOXO1, TGF-ß regulation and wound healing.

Re-epithelialization is a complex process that involves migration and proliferation of keratinocytes, in addition to the production of cytokines and growth factors that affect other cells. The induction of transcription factors during these processes is crucial for successful wound healing. The transcription factor forkhead boxO-1 (FOXO1) has recently been found to be an important regulator of wound healing. In particular, FOXO1 has significant effects through regulation of transforming growth factor-beta (TGF-ß) expression and protecting keratinocytes from oxidative stress. In the absence of FOXO1, there is increased oxidative damage, reduced TGF-ß1 expression, reduced migration and proliferation of keratinocytes and increased keratinocytes apoptosis leading to impaired re-epithelialization of wounds.

Cardiac sarcoidosis in the donor heart without extracardiac manifestations.

A middle-aged woman who received heart transplantation for end-stage sarcoid cardiomyopathy developed recurrent cardiac sarcoidosis in the donor heart. She presented 5 years post-transplantation with heart block and systolic dysfunction, without extracardiac involvement. Her disease was unresponsive to corticosteroids. Routine functional imaging may help identify such recurrences.

Controlled trial to improve resident sign-out in a medical intensive care unit.

OBJECTIVE: Poor sign-out or handover of care may lead to preventable patient harm. Critically ill patients in intensive care units (ICU) are complex and prone to rapid clinical deterioration. If clinical deterioration occurs, timeliness of appropriate interventions is essential to prevent or reduce adverse outcomes. Therefore sign-outs need to efficiently transmit key information and provide anticipatory guidance. Interventions to improve resident-to-resident ICU sign-outs have not been well described. We conducted a controlled trial to test the effectiveness of a standardised ICU sign-out process to the usual ICU sign-out. DESIGN: Prospective controlled trial. SETTING: A 26-bed medical intensive care unit (MICU) in an urban tertiary academic medical centre. SUBJECTS: Residents rotating through the MICU. INTERVENTIONS: ICU-specific written sign-out template. METHODS: Residents completed postcall surveys assessing satisfaction with verbal and written sign-outs and incidence of non-routine events. Our main outcome of interest was the occurrence of non-routine events. MAIN RESULTS: Compared with the intervention group, on significantly more nights, night float residents in the control group encountered patients who were sicker than sign-out would have suggested (15.94% vs 43.75%; p<0.0001). On significantly fewer nights, night float residents in the intervention group indicated that either something happened to patients that was unexpected (18.84% vs 36.51%; p=0.023) or they were insufficiently prepared for (4.35% vs 35.94%; p<0.0001). Similarly, on fewer nights, residents in the intervention group indicated that they had to perform interventions that were unplanned or unanticipated (15.9% vs 37.7%; p=0.005). CONCLUSION: A structured sign-out process compared with usual sign-out significantly reduced the occurrence of non-routine events in an academic MICU.

Validation of the colour difference plot scoring system analysis of the 103 hexagon multifocal electroretinogram in the evaluation of hydroxychloroquine retinal toxicity.

PURPOSE: To evaluate sensitivity, specificity and reproducibility of colour difference plot analysis (CDPA) of 103 hexagon multifocal electroretinogram (mfERG) in detecting established hydroxychloroquine (HCQ) retinal toxicity. METHODS: Twenty-three patients taking HCQ were divided into those with and without retinal toxicity and were compared with a control group without retinal disease and not taking HCQ. CDPA with two masked examiners was performed using age-corrected mfERG responses in the central ring (Rc ; 0-5.5 degrees from fixation) and paracentral ring (Rp ; 5.5-11 degrees from fixation). An abnormal ring was defined as containing any hexagons with a difference in two or more standard deviations from normal (colour blue or black). RESULTS: Categorical analysis (ring involvement or not) showed Rc had 83% sensitivity and 93% specificity. Rp had 89% sensitivity and 82% specificity. Requiring abnormal hexagons in both Rc and Rp yielded sensitivity and specificity of 83% and 95%, respectively. If required in only one ring, they were 89% and 80%, respectively. In this population, there was complete agreement in identifying toxicity when comparing CDPA using Rp with ring ratio analysis using R5/R4 P1 ring responses (89% sensitivity and 95% specificity). Continuous analysis of CDPA with receiver operating characteristic analysis showed optimized detection (83% sensitivity and 96% specificity) when ≥4 abnormal hexagons were present anywhere within the Rp ring outline. Intergrader agreement and reproducibility were good. CONCLUSIONS: Colour difference plot analysis had sensitivity and specificity that approached that of ring ratio analysis of R5/R4 P1 responses. Ease of implementation and reproducibility are notable advantages of CDPA.