Planar microdevices enhance transport of large molecular weight molecules across retinal pigment epithelial cells

Large molecular weight drug delivery to the posterior eye is challenging due to cellular barriers that hinder drug transport. Understanding how to enhance transport across the retinal barrier is important for the design of new drug delivery systems. A novel mechanism to enhance drug transport is the use of geometric properties, which has not been extensively explored in the retina. Planar SU-8/Poly(ethyleneglycol)dimethacrylate microdevices were constructed using photolithography to deliver FITC dextran across an in vitro retinal model. The model consists of retinal pigment epithelial (RPE) cells grown to confluence on transwell inserts, which provides an environment to investigate the influence of geometry on paracellular and transcellular delivery of encapsulated large molecules. Planar microdevices enhanced transport of large molecular weight dextrans across different models of RPE in a size dependent fashion. Increased drug permeation across the RPE was observed with the addition of microdevices as compared to a traditional bolus of FITC dextran. This phenomena was initiated by a non-toxic interaction between the microdevices and the retinal tight junction proteins. Suggesting that increased drug transport occurs via a paracellular pathway. These experiments provide evidence to support the future use of planar unidirectional microdevices for delivery of biologics in ocular applications.     

Erythema ab igne with features resembling keratosis lichenoides chronica

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low‐grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.     

Intraoperative fluid administration volumes during pediatric liver transplantation and postoperative outcomes: A multicenter analysis

Introduction

Fluid administration is an important aspect of the management of children undergoing liver transplantation and may impact postoperative outcomes. Our aim was to evaluate the association between volume of intraoperative fluid administration and our primary outcome, the duration of postoperative mechanical ventilation following pediatric liver transplantation. Secondary outcomes included intensive care unit length of stay and hospital length of stay.

Methods

We conducted a multicenter, retrospective cohort study using electronic data from three major pediatric liver transplant centers. Intraoperative fluid administration was indexed to weight and duration of anesthesia. Univariate and stepwise linear regression analyses were conducted.

Results

Among 286 successful pediatric liver transplants, the median duration of postoperative mechanical ventilation was 10.8 h (IQR 0.0, 35.4), the median intensive care unit length of stay was 4.3 days (IQR 2.7, 6.8), and the median hospital length of stay was 13.6 days (9.8, 21.1). Univariate linear regression showed a weak correlation between intraoperative fluids and duration of ventilation (r² = .037, p = .001). Following stepwise linear regression, intraoperative fluid administration remained weakly correlated (r² = .161, p = .04) with duration of postoperative ventilation. The following variables were also independently correlated with duration of ventilation: center (Riley Children's Health versus Children's Health Dallas, p = .001), and open abdominal incision after transplant (p = .001).

Discussion

The amount of intraoperative fluid administration is correlated with duration of postoperative mechanical ventilation in children undergoing liver transplantation, however, it does not seem to be a strong factor.

Conclusions

Other modifiable factors should be sought which may lead to improved postoperative outcomes in this highly vulnerable patient population.