Tunable alginate hydrogels as injectable drug delivery vehicles for optic neuropathy.

Many disease pathologies, particularly in the eye, are induced by oxidative stress. In particular, injury to the optic nerve (ON), or optic neuropathy, is one of the most common causes of vision loss. Traumatic optic neuropathy (TON) occurs when the ON is damaged following blunt or penetrating trauma to either the head or eye. Currently, there is no effective treatment for TON, only management options, namely the systematic delivery of corticosteroids and surgical decompression of the optic nerve. Unfortunately, neither option alleviates the generation of reactive oxygen species (ROS) which are responsible for downstream damage to the ON. Additionally, the systemic delivery of corticosteroids can cause fatal off-target effects in cases with brain involvement. In this study, we developed a tunable injectable hydrogel delivery system for local methylene blue (MB) delivery using an internal method of crosslinking. MB was chosen due to its ROS scavenging ability and neuroprotective properties. Our MB-loaded polymeric scaffold demonstrated prolonged release of MB as well as in situ gel formation. Additionally, following rheological characterization, these alginate hydrogels demonstrated minimal cytotoxicity to human retinal pigment epithelial cells in vitro and exhibited injection feasibility through small-gauge needles. Our chosen MB concentrations displayed a high degree of ROS scavenging following release from the alginate hydrogels, suggesting this approach may be successful in reducing ROS levels following ON injury, or could be applied to other ocular injuries.

Risk of adverse events associated with upper and lower endoscopic ultrasound: a population-based cohort study.

Background and study aim Endoscopic ultrasound (EUS) enables diagnostic evaluation and therapeutic interventions but is associated with adverse events. We conducted a population-based cohort study to determine the risk of adverse events for upper and lower EUS with and without fine-needle aspiration (FNA). Patients and methods All adults who underwent EUS and resided in Calgary in 2007-2013 were included. Endoscopy and provincial databases were used to identify EUS procedures, unplanned emergency department visits, and hospital admissions within 30 days of the procedures, which were then characterized through formal chart review. Adverse events were defined a priori and classified as definitely, possibly, or not related to EUS. The primary outcome was 30-day risk of adverse events classified as definitely or possibly related to EUS. Univariable and multivariable analyses were conducted with risk factors known to be associated with EUS adverse events. Results 2895 patients underwent 3552 EUS procedures: 3034 (85 %) upper EUS, of which 710 (23 %) included FNA, and 518 (15 %) lower EUS, of which 23 (4 %) involved FNA. Overall, 69 procedures (2 %) involved an adverse event that was either definitely or possibly related to EUS, with 33 (1 %) requiring hospitalization. None of the adverse events required intensive care or resulted in death. On multivariable analysis, only FNA was associated with increased risk of adverse events (odds ratio 6.43, 95 % confidence interval 3.92-10.55; P  < 0.001). Conclusion Upper and lower EUS were generally safe but FNA substantially increased the risk of adverse events. EUS-related complications requiring hospitalization were rare.

Macro- and Microscale Properties of the Vitreous Humor to Inform Substitute Design and Intravitreal Biotransport.

Research on the vitreous humor and development of hydrogel vitreous substitutes have gained a rapid increase in interest within the past two decades. However, the properties of the vitreous humor and vitreous substitutes have yet to be consolidated. In this paper, the mechanical properties of the vitreous humor and hydrogel vitreous substitutes were systematically reviewed. The number of publications on the vitreous humor and vitreous substitutes over the years, as well as their respective testing conditions and testing techniques were analyzed. The mechanical properties of the human vitreous were found to be most similar to the vitreous of pigs and rabbits. The storage and loss moduli of the hydrogel vitreous substitutes developed were found to be orders of magnitude higher in comparison to the native human vitreous. However, the reported modulus for human vitreous, which was most commonly tested in vitro, has been hypothesized to be different in vivo. Future studies should focus on testing the mechanical properties of the vitreous in situ or in vivo. In addition to its mechanical properties, the vitreous humor has other biotransport mechanisms and biochemical functions that establish a redox balance and maintain an oxygen gradient inside the vitreous chamber to protect intraocular tissues from oxidative damage. Biomimetic hydrogel vitreous substitutes have the potential to provide ophthalmologists with additional avenues for treating and controlling vitreoretinal diseases while preventing complications after vitrectomy. Due to the proximity and interconnectedness of the vitreous humor to other ocular tissues, particularly the lens and the retina, more interest has been placed on understanding the properties of the vitreous humor in recent years. A better understanding of the properties of the vitreous humor will aid in improving the design of biomimetic vitreous substitutes and enhancing intravitreal biotransport.

Cohort profile: The Forzani & MacPhail Colon Cancer Screening Centre biorepository, Calgary, Alberta.

PURPOSE: The Colon Cancer Screening Centre (CCSC) biorepository (Calgary, Canada) supports a wide range of research topics related to colorectal cancer (CRC) by collecting, and storing biospecimens (blood, urine, normal colon tissue) from consenting patient participants. Housing unique biospecimens along with detailed participant lifestyle and health history questionnaire data, the CCSC biorepository can support a variety of research related to CRC risk factors, biomarkers, genetic causes and more. PARTICIPANTS: Currently, 2292 average risk CRC patients have consented to participate in the CCSC cohort and have provided stored biospecimens. The collected samples and data provide important high-quality materials for research, discovery and evaluation related to CRC screening and carcinogenesis and is available for access by outside researchers. In addition to biological samples, the CCSC collects detailed patient information on their lifestyle, physical activity and dietary patterns through questionnaires at the time of their enrolment. FINDINGS TO DATE: The majority of participants (75%) are between 50 and 64 years of age. Women make up 46% (1055) of the cohort. Additional characteristics of the cohort included 44% reporting a body mass index of 25-30 kg/m2 (overweight), 53% having never smoked tobacco and 13% having a family member with CRC. FUTURE PLANS: The CCSC cohort plans to include the recruitment of high risk CRC cohorts. High-risk participants would comprise patients with a positive faecal immunochemical test and family history of CRC.

Development of a definition and rules for causal attribution of post-colonoscopy bleeding.

BACKGROUND: Post-colonoscopy bleeding (PCB) is an important colonoscopy quality indicator that is recommended to be routinely collected by colorectal cancer screening programs and endoscopy quality improvement programs. We created a standardized and reliable definition of PCB and set of rules for attributing the relatedness of PCB to a colonoscopy. METHODS: PCB events were identified from colonoscopies performed at the Forzani & MacPhail Colon Cancer Screening Centre. Existing definitions and relatedness rules for PCB were reviewed by the authors and a draft definition and set of rules was created. The definition and rules were revised after initial testing was performed using a set of 15 bleeding events. Information available for each event included the original endoscopy report and data abstracted from the emergency or inpatient record by a trained research assistant. A validation set of 32 bleeding events were then reviewed to assess their interrater reliability by having three endoscopists and one research assistant complete independent reviews and three endoscopists complete a consensus review. The Kappa statistic was used to measure interrater reliability. RESULTS: The panel classified 28 of 32 events as meeting the definition of PCB and rated 7, 8 and 6 events as definitely, probably and possibly related to the colonoscopy, respectively. The Kappa for the definition of PCB for the three independent reviews was 0.82 (substantial agreement). The Kappa for the attribution of the PCB to the colonoscopy by the three endosocopists was 0.74 (substantial agreement). The research assistant had a high agreement with the panel for both the definition (100% agreement) and application of the causal criteria (kappa 0.95). CONCLUSIONS: A standardized definition of PCB and attribution rules achieved high interrater reliability by endoscopists and a non-endoscopist and provides a template of required data for event adjudication by screening and quality improvement programs.

Prophylactic Endoscopic Clipping Does Not Prevent Delayed Postpolypectomy Bleeding in Routine Clinical Practice: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Delayed postpolypectomy bleeding (DPPB) is a relatively common adverse event. Evidence is conflicting on the efficacy of prophylactic clipping to prevent DPPB, and real-world effectiveness data are lacking. We aimed to determine the effectiveness of prophylactic clipping in preventing DPPB in a large screening-related cohort. METHODS: We manually reviewed records of patients who underwent polypectomy from 2008 to 2014 at a screening facility. Endoscopist-, patient- and polyp-related data were collected. The primary outcome was DPPB within 30 days. All unplanned healthcare visits were reviewed; DPPB cases were adjudicated by committee using a criterion-based lexicon. Multivariable logistic regression was performed, yielding adjusted odds ratios (AORs) for the association between clipping and DPPB. Secondary analyses were performed on procedures where one polyp was removed, in addition to propensity score-matched and subgroup analyses. RESULTS: In total, 8,366 colonoscopies involving polypectomy were analyzed, yielding 95 DPPB events. Prophylactic clipping was not associated with reduced DPPB (AOR 1.27; 0.83-1.96). These findings were similar in the single-polyp cohort (n = 3,369, AOR 1.07; 0.50-2.31). In patients with one proximal polyp ≥20 mm removed, there was a nonsignificant AOR with clipping of 0.55 (0.10-2.66). Clipping was not associated with a protective benefit in the propensity score-matched or other subgroup analyses. DISCUSSION: In this large cohort study, prophylactic clipping was not associated with lower DPPB rates. Endoscopists should not routinely use prophylactic clipping in most patients. Additional effectiveness and cost-effectiveness studies are required in patients with proximal lesions ≥20 mm, in whom there may be a role for prophylactic clipping.

Practice patterns and predictors of prophylactic endoscopic clip usage during polypectomy.

Background and study aims Prophylactic endoscopic clips are commonly placed during polypectomy to reduce risk of delayed bleeding, although evidence to support this practice is unclear. Our study aimed to: (1) identify variables associated with prophylactic clip use; (2) explore variability between endoscopists' clipping practices and (3) study temporal trends in prophylactic clip use. Patients and methods This was a retrospective cohort study in a high-volume unit dedicated to screening-related colonoscopies. Colonoscopies involving polypectomy from 2008 to 2014 were reviewed. The primary outcome was prophylactic clipping status, both at the patient level and per polyp. Hierarchical regression models yielded adjusted odds ratios (AORs) to determine predictors of prophylactic clipping. Results A total of 8,366 colonoscopies involving 19,129 polypectomies were included. Polyp size ≥ 20 mm was associated with higher clip usage (AOR 2.94; 95 % CI: 2.43, 3.54) compared to polyps < 10 mm. Right-sided polyps were more likely to be clipped (AOR 2.78; 95 % CI: 2.34, 3.30) relative to the rectum. Surgeons clipped less than gastroenterologists (OR 0.52; 95 % CI: 0.44, 0.63). From 2008 to 2014, the crude proportion of prophylactically clipped cases increased by 7.4 % (95 % CI: 7.1, 7.6) from 1.9 % to 9.3 %. Significant inter-endoscopist variability in clipping practices was observed, notably, for polyps < 10 mm. Conclusions Prophylactic clip usage was correlated with established risk factors for delayed bleeding. Significantly increased clip usage over time was shown. Given that evidence does not clearly support prophylactic clipping, there is a need to educate practitioners and limit healthcare resource utilization.

Current Recommendations for the Diagnosis of Acute and Chronic PJI for Hip and Knee-Cell Counts, Alpha-Defensin, Leukocyte Esterase, Next-generation Sequencing.

PURPOSE OF REVIEW: Despite significant progress in recent years, the diagnosis of periprosthetic joint infection (PJI) remains a challenge and no gold standard test exists. A combination of serological, synovial, microbiological, histological, and radiological investigations is performed that are expensive, often invasive, and imperfect. Novel biomarkers and molecular methods have shown promise in recent years. The purpose of this review is to provide an update about the diagnostic recommendations for PJI and cover a selection of emerging diagnostic tools. RECENT FINDINGS: Recent literature highlights a new evidence-based definition for diagnosing hip and knee PJI that shows excellent performance on formal external multi-institutional validation. There is also increasing evidence to support the measurement of selected biomarkers in serum and synovial fluid, such as alpha-defensin, D-dimer, and interleukin-6. Finally, the emerging utility of next-generation sequencing for pathogen identification is discussed. In summary, we describe current recommendations and emerging tests for the diagnosis of PJI. Residual limitations and directions for future research are also discussed.