Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications

Coats’ Disease-Related Macular Edema Treated with Combined Aflibercept and Laser Photocoagulation

Purpose. To describe the clinical response of refractory macular edema associated with Coats’ disease following treatment with aflibercept and laser photocoagulation. Methods. Case report. Results. A 17-year-old female presented with decreased vision of the left eye. Ophthalmic exam demonstrated intraretinal hemorrhages and exudation with associated edema centrally. Angiographic evaluation revealed central leaking microaneurysms and peripheral capillary dropout. These findings and a systemic work-up that yielded an incidental Factor V Leiden mutation lead to a diagnosis of Coats’ disease. Initial treatment consisted of laser photocoagulation and intravitreal bevacizumab but with poor response. Switching to intravitreal aflibercept resulted in resolution of the refractory macular edema and improvement of visual acuity to 20/25 in the left eye. Conclusion. We describe a case of refractory macular edema which responded more favorably to intravitreal aflibercept compared with bevacizumab when combined with laser photocoagulation in a patient with Coats’ disease

Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1)

PURPOSE: To evaluate the efficacy, safety, and injection frequency of vascular endothelial growth factor (VEGF) inhibitors as used in clinical practice for the treatment of diabetic macular edema. METHODS: Multicenter (10 sites), retrospective chart review in patients (n=156) who received ≥3 anti-VEGF injections. Data collected for ≥6 months after the first injection included Snellen best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by time-domain or spectral-domain optical coherence tomography (TD-OCT or SD-OCT). RESULTS: Mean number of anti-VEGF injections (627 bevacizumab, 594 ranibizumab, 1 aflibercept) was 5.8 (year 1), 5.0 (year 2), and 3.4 (year 3). Percentage of patients with BCVA of 20/40 or better and CRT ≤250 μm on TD-OCT or ≤300 μm on SD-OCT at the same visit (primary endpoint) ranged from 16.4% to 38.9% after the first 10 injections; 51.9%–62.3% achieved ≥20/40 BCVA and 26.2%–48.0% met CRT criteria. Therapy was well tolerated with 19 treatment-related adverse events (all ocular) reported. CONCLUSION: Anti-VEGF injections were administered less frequently and were less effective than those in the ranibizumab registration trials. After each of the first 9 injections, <25% of patients achieved both BCVA of 20/40 or better and a dry macula. A substantial proportion of patients are suboptimal responders to anti-VEGF therapy; these patients may be candidates for other therapies, including intravitreal corticosteroid and laser therapy

Association Between Neuromuscular Blocking Agents and Outcomes of Emergency Tracheal Intubation: A Secondary Analysis of Randomized Trials

Study objective: To examine the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt and severe complications during tracheal intubation of critically ill adults in an emergency department (ED) or ICU. Methods: We performed a secondary analysis of data from 2 multicenter randomized trials in critically ill adults undergoing tracheal intubation in an ED or ICU. Using a generalized linear mixed-effects model with prespecified baseline covariates, we examined the association between the neuromuscular blocking agent received (succinylcholine versus rocuronium) and the incidences of successful intubation on the first attempt (primary outcome) and severe complications during tracheal intubation (secondary outcome). Results: Among the 2,440 patients in the trial data sets, 2,339 (95.9%) were included in the current analysis; 475 patients (20.3%) received succinylcholine and 1,864 patients (79.7%) received rocuronium. Successful intubation on the first attempt occurred in 375 patients (78.9%) who received succinylcholine and 1,510 patients (81.0%) who received rocuronium (an adjusted odds ratio of 0.87; 95% CI 0.65 to 1.15). Severe complications occurred in 67 patients (14.1%) who received succinylcholine and 456 patients (24.5%) who received rocuronium (adjusted odds ratio, 0.88; 95% CI 0.62 to 1.26). Conclusion: Among critically ill adults undergoing tracheal intubation, the incidences of successful intubation on the first attempt and severe complications were not significantly different between patients who received succinylcholine and patients who received rocuronium

Fluid Accumulation After Neonatal Congenital Cardiac Surgery; Clinical Implications and Outcomes

BACKGROUND To determine the association between fluid balance metrics and mortality and other postoperative outcomes after neonatal cardiac surgery in a contemporary multi-center cohort. METHODS Observational cohort study across 22 hospitals in neonates (≤30 days) undergoing cardiac surgery. We explored overall % fluid overload, postoperative day 1 % fluid overload, peak % fluid overload, and time to first negative daily fluid balance. The primary outcome was in-hospital mortality. Secondary outcomes included postoperative duration of mechanical ventilation, and intensive care unit (ICU) and hospital length of stay. Multivariable logistic or negative binomial regression was used to determine independent associations between fluid overload variables and each outcome. RESULTS The cohort included 2223 patients. In-hospital mortality was 3.9% (n=87). Overall median peak % fluid overload was 4.9%, (interquartile range 0.4-10.5%). Peak % fluid overload and postoperative day 1 % fluid overload were not associated with primary or secondary outcomes. Hospital resource utilization increased on each successive day of not achieving a first negative daily fluid balance and was characterized by longer duration of mechanical ventilation (incidence rate ratio 1.11, 95% confidence interval 1.08-1.14, ICU length of stay (incidence rate ratio 1.08, 95% confidence interval 1.03-1.12), and hospital length of stay (incidence rate ratio 1.09, 95% confidence interval 1.05-1.13). CONCLUSIONS Time to first negative daily fluid balance, but not % fluid overload is associated with improved postoperative outcomes in neonates after cardiac surgery. Specific treatments to achieve an early negative fluid balance may decrease postoperative care durations

Workers’ Views of the Impact of Trade on Jobs

Although public policy is influenced by the perception that workers worry about the impact of trade on their jobs, there is little empirical evidence on what shapes such views. This paper uses new data to examine how workers' perceptions of the impact of trade are related to their career paths, job characteristics, and local labor market conditions. Surprisingly, given prior literature, we find that workers' perceptions primarily reflect local labor market conditions and education rather than labor market experiences or job characteristics

Large-Scale Automated Histology in the Pursuit of Connectomes

How does the brain compute? Answering this question necessitates neuronal connectomes, annotated graphs of all synaptic connections within defined brain areas. Further, understanding the energetics of the brain's computations requires vascular graphs. The assembly of a connectome requires sensitive hardware tools to measure neuronal and neurovascular features in all three dimensions, as well as software and machine learning for data analysis and visualization. We present the state of the art on the reconstruction of circuits and vasculature that link brain anatomy and function. Analysis at the scale of tens of nanometers yields connections between identified neurons, while analysis at the micrometer scale yields probabilistic rules of connection between neurons and exact vascular connectivity