Determining the learning curve for a novel microsurgical procedure using histopathology.

PURPOSE: Wet laboratories are becoming an increasingly important training tool as part of a push to a proficiency-based training model. We created a microsurgical wet laboratory to investigate the utility of histopathology use in assessing surgical outcomes and determine the learning curve of a novel microsurgical procedure. METHODS: A microsurgical wet laboratory was established using pig eyes to simulate the human cornea. Three novice surgeons and an experienced surgeon performed an anterior cornea lamellar dissection and the duration of the procedure was recorded. With the aid of histological analysis, the thickness and characteristics of the dissected graft was recorded. The number of attempts to complete the experiment, defined as three successful dissections with mean thickness below 100 µm, was documented. RESULTS: The use of histopathology was highly successful allowing in-depth analysis of the dissected graft for each attempt. Trainees reached the endpoint of the study in 21, 26 and 36 attempts (mean: 28 attempts) whilst the corneal surgeon completed the experiment in 12 attempts (p = 0.07). Mean dissection thickness decreased over time for all participants. The mean dissection time for trainees was 10.6 ± 4.2 min compared to the corneal surgeon with a mean of 8.2 ± 3.1 min (p = 0.03). CONCLUSION: We propose a corneal wet laboratory model that allows for simple, efficient, and flexible microsurgical training. The use of histopathological analysis allows for careful graft analysis, providing objective feedback throughout the training exercise. Trainees demonstrated improvements in the three key aspects of the procedure: accuracy as evidenced by decreasing histological thickness, confidence by self-report and fluidity by decreasing duration of the procedure.

Open globe injuries: Epidemiology, visual and surgical predictive variables, prognostic models, and economic cost analysis.

BACKGROUND: Open globe injuries (OGI) represent a visually and economically devastating cause of vision loss. We examined the epidemiology, predictive variables, prognostic models, and economic cost of surgically managed OGI. METHODS: A retrospective tertiary centre study from 2008 to 2018 of 155 consecutive OGI in individuals aged 16 and older was performed. Medical records review, application of Ocular Trauma Score (OTS) and Classification and Regression Tree Analysis (CART) and cost analysis were undertaken. Key outcomes measured were visual acuity, number of operating theatre visits, prognostication using OTS and CART and estimated costs. RESULTS: Younger males at work with inadequate protective eyewear (89.1%) and falls in the elderly were overrepresented. Inferior visual outcomes were associated with a more severe OTS score, a larger injury zone, increasing age, the presence of retinal detachment, extraocular muscle involvement, intraocular foreign body, and globe rupture (R2  = 0.723, p < 0.001). Multiple operating theatre visits were required in the presence of retinal detachment, lens or orbit involvement, work-related injury, globe rupture, and a history of previous intraocular surgery (R2  = 0.0423, p < 0.001). Both OTS and CART prognosticated outcomes (p < 0.001). The OTS predicted for no vision (no light perception/enucleation/evisceration) and profound visual loss (worse than 6/120; specificity: both 100%, sensitivity: 88.2% and 88%) whereas the CART predicted for visual survival (light perception or better) and minimal-to-severe visual loss (6/120 or better; specificity: 88.5% and 81.7% , sensitivity: 97.7% and 100%). Estimated annual OGI cost for Australia was AUD48.1-60.5 million (USD37.3-47.0 million). CONCLUSIONS: The total cost of OGI is immense with young males and the elderly being disproportionately affected. Implementation of targeted government legislation and public health preventative measures may be cost-effective in ameliorating the significant burden.

Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior.

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8-12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.

Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep.

Intrauterine growth restriction (IUGR) increases the risk of adult type 2 diabetes (T2D) and obesity. Neonatal exendin-4 treatment can prevent diabetes in the IUGR rat, but whether this will be effective in a species where the pancreas is more mature at birth is unknown. Therefore, we evaluated the effects of neonatal exendin-4 administration after experimental restriction of placental and fetal growth on growth and adult metabolic outcomes in sheep. Body composition, glucose tolerance, and insulin secretion and sensitivity were assessed in singleton-born adult sheep from control (CON; n = 6 females and 4 males) and placentally restricted pregnancies (PR; n = 13 females and 7 males) and in sheep from PR pregnancies that were treated with exendin-4 as neonates (daily sc injections of 1 nmol/kg exendin-4; PR + exendin-4; n = 11 females and 7 males). Placental restriction reduced birth weight (by 29%) and impaired glucose tolerance in the adult but did not affect adult adiposity, insulin secretion, or insulin sensitivity. Neonatal exendin-4 suppressed growth during treatment, followed by delayed catchup growth and unchanged adult adiposity. Neonatal exendin-4 partially restored glucose tolerance in PR progeny but did not affect insulin secretion or sensitivity. Although the effects on glucose tolerance are promising, the lack of effects on adult body composition, insulin secretion, and insulin sensitivity suggest that the neonatal period may be too late to fully reprogram the metabolic consequences of IUGR in species that are more mature at birth than rodents.