Advances in 3D bioprinting technology for functional corneal reconstruction and regeneration.

Corneal transplantation constitutes one of the major treatments in severe cases of corneal diseases. The lack of cornea donors as well as other limitations of corneal transplantation necessitate the development of artificial corneal substitutes. Biosynthetic cornea model using 3D printing technique is promising to generate artificial corneal structure that can resemble the structure of the native human cornea and is applicable for regenerative medicine. Research on bioprinting artificial cornea has raised interest into the wide range of materials and cells that can be utilized as bioinks for optimal clarity, biocompatibility, and tectonic strength. With continued advances in biomaterials science and printing technology, it is believed that bioprinted cornea will eventually achieve a level of clinical functionality and practicality as to replace donated corneal tissues, with their associated limitations such as limited or unsteady supply, and possible infectious disease transmission. Here, we review the literature on bioprinting strategies, 3D corneal modelling, material options, and cellularization strategies in relation to keratoprosthesis design. The progress, limitations and expectations of recent cases of 3D bioprinting of artifial cornea are discussed. An outlook on the rise of 3D bioprinting in corneal reconstruction and regeneration is provided.

Potassium disturbance associated with an inpatient childhood asthma pathway.

BACKGROUND: Paediatric asthma exacerbations in Alberta are treated via standardized order sets known as the Alberta Acute Childhood Asthma Pathway (ACAP). This pathway is utilized in paediatric tertiary hospitals and in remote and rural locations. Incidence, magnitude, and risk factors for hypokalemia in inpatients receiving salbutamol for asthma exacerbations via this pathway are presently unknown. OBJECTIVE: Establish incidence, magnitude, and risk factors for hypokalemia associated with salbutamol therapy as directed by a paediatric asthma pathway. METHODS: Retrospective cohort study using visit-level electronic medical data. Inpatients aged <18 years old receiving salbutamol via the ACAP with at least one potassium level were included. Hypokalemia was defined as mild (3.0 ≤ [K+] < 3.5 mEq/L), moderate (2.5 ≤ [K+] < 3.0 mEq/L), or severe ([K+] < 2.5 mEq/L), as measured in serum or blood gas. Binomial logistic regression was utilized to examine risk factors for hypokalemia, route of administration, location of lowest [K+], nil per os (NPO) status during admission, potassium supplementation, gender, and age. RESULTS: There were 821 patients screened for analysis and 433 patients were analyzed after exclusions. There was an incidence of hypokalemia of 38.8%. Of patients experiencing hypokalemia, 71.4% were mild, 25.6% moderate, and 3.0% severe. Risk factors included nebulized salbutamol, patient location (emergency department or paediatric intensive care unit), and age (>5 years) although these risk factors may actually represent patients receiving higher doses of salbutamol. CONCLUSIONS: The majority of the 38.8% of children experiencing hypokalemia associated with the ACAP were mild. Routine monitoring of potassium status in children receiving salbutamol per standardized pathway is recommended for children with described risk factors, and ideally within the first 12 hours of presentation.

Mapping glycan-mediated galectin-3 interactions by live cell proximity labeling.

Galectin-3 is a glycan-binding protein (GBP) that binds ß-galactoside glycan structures to orchestrate a variety of important biological events, including the activation of hepatic stellate cells and regulation of immune responses. While the requisite glycan epitopes needed to bind galectin-3 have long been elucidated, the cellular glycoproteins that bear these glycan signatures remain unknown. Given the importance of the three-dimensional (3D) arrangement of glycans in dictating GBP interactions, strategies that allow the identification of GBP receptors in live cells, where the native glycan presentation and glycoprotein expression are preserved, have significant advantages over static and artificial systems. Here we describe the integration of a proximity labeling method and quantitative mass spectrometry to map the glycan and glycoprotein interactors for galectin-3 in live human hepatic stellate cells and peripheral blood mononuclear cells. Understanding the identity of the glycoproteins and defining the structures of the glycans will empower efforts to design and develop selective therapeutics to mitigate galectin-3-mediated biological events.

The Effect of Time to Castration Resistance on Outcomes With Abiraterone and Enzalutamide in Metastatic Prostate Cancer.

BACKGROUND: Abiraterone and enzalutamide are 2 novel androgen receptor (AR)-targeting therapies that improve survival in patients with metastatic castration-resistant prostate cancer. The factors that predict abiraterone and enzalutamide response are lacking. The objective of the present study was to determine whether the outcomes from primary androgen deprivation therapy (ADT) could predict the outcomes with subsequent novel AR-targeting therapies. MATERIALS AND METHODS: We identified 80 consecutive patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide. Cox regression models were used to analyze the relationships between the primary ADT response and the primary outcome of progression-free survival (PFS) after initiating novel hormonal therapy. The secondary outcomes included prostate-specific antigen decline and overall survival. The survival probabilities were plotted using the Kaplan-Meier method, and the differences assessed with the log-rank test. RESULTS: The time to castration resistance with primary ADT showed a significant association with both PFS and overall survival after initiating novel hormone therapy (P = .032 and P = .028, respectively). Patients with progression during primary ADT before 1 year had a median PFS of 3.4 months compared with a median PFS of 7.6 and 8.1 months for patients whose time to castration resistance was ≥ 1 and ≤ 5 years (P = .008) and > 5 years (P = .026), respectively. However, the time to castration resistance was not an independent predictor of survival or the PSA response with novel AR-targeting therapy on multivariate analysis. CONCLUSION: A rapid time to progression during primary ADT was associated with poor outcomes but was not an independent predictor of the response to enzalutamide or abiraterone.

Outcomes of multidisciplinary management in pediatric low-grade gliomas.

PURPOSE: To evaluate the outcomes in pediatric low-grade gliomas managed in a multidisciplinary setting. METHODS AND MATERIALS: We conducted a single-institution retrospective study of 181 children with Grade I-II gliomas. Log-rank and stepwise Cox proportional hazards models were used to analyze freedom from progression (FFP) and overall survival (OS). RESULTS: Median follow-up was 6.4 years. Thirty-four (19%) of patients had neurofibromatosis Type 1 (NF1) and because of their favorable prognosis were evaluated separately. In the 147 (81%) of patients without NF1, actuarial 7-year FFP and OS were 67 ± 4% (standard error) and 94 ± 2%, respectively. In this population, tumor location in the optic pathway/hypothalamus was associated with worse FFP (39% vs. 76%, p < 0.0003), but there was no difference in OS. Age ≤5 years was associated with worse FFP (52% vs. 75%, p < 0.02) but improved OS (97% vs. 92%, p < 0.05). In those with tissue diagnosis, gross total resection (GTR) was associated with improved 7-year FFP (81% vs. 56%, p < 0.02) and OS (100% vs. 90%, p < 0.03). In a multivariate model, only location in the optic pathway/hypothalamus predicted worse FFP (p < 0.01). Fifty patients received radiation therapy (RT). For those with less than GTR, adjuvant RT improved FFP (89% vs. 49%, p < 0.003) but not OS. There was no difference in OS between patient groups given RT as adjuvant vs. salvage therapy. In NF1 patients, 94% of tumors were located in the optic pathway/hypothalamus. With a conservative treatment strategy in this population, actuarial 7-year FFP and OS were 73 ± 9% and 100%, respectively. CONCLUSIONS: Low-grade gliomas in children ≤5 years old with tumors in the optic pathway/hypothalamus are more likely to progress, but this does not confer worse OS because of the success of salvage therapy. When GTR is not achieved, adjuvant RT improves FFP but not OS. Routine adjuvant RT can be avoided and instead reserved as salvage.