Impact of the faecal immunochemical test on colorectal cancer survival.

BACKGROUND: There is already evidence that the faecal immunochemical test (FIT) is a useful tool for the diagnosis of colorectal cancer (CRC) that helps to identify symptomatic patients requiring early colonoscopy. Although the recommendation to use FIT is widely accepted, there are no data concerning whether this strategy improves patient survival.The objective was to assess whether the survival is higher if CRC patients have been first diagnosed by FIT (as compared with the rest of patients with CRC). METHODS: We identified all cases of CRC diagnosed between 2009 and 2016 in Donostialdea (Spain), excluding all the CRC detected in population screening. We focused on symptomatic patients. One thousand five hundred twenty-seven cases of CRC were divided into two groups based on the route to diagnosis: group 1: individuals who tested positive in a FIT during the year before diagnosis, and group 2: others.Survival was assessed by Kaplan-Meier estimation, and with the log-rank test. A Cox regression model was used to adjust for differences between groups due to other variables associated with survival. RESULTS: One thousand nine hundred sixty-seven cases of invasive CRC were identified, of which 22.4% were detected in population screening. Of the 1527 cases diagnosed in symptomatic patients, 317 patients had undergone a FIT in the year before the diagnosis of CRC. In 279 cases(18.3%), the result had been positive and this was the first step towards their CRC diagnosis (group 1). Group 2 was composed of the 1248 cases of CRC (81.7%). Considering these cases, 1210 patients with CRC did not undergo any FIT while 38 patients presented a negative result in the year before the diagnosis. The rate of early-stage disease (stage I or II) was higher in group 1 (51.3% vs 45.5% in group 2) (p = 0.04). Furthermore, the 3-year survival was longer in group 1 (72% vs 59% in group 2) (HR 1.50; 95% CI 1.22-1.84).The variables independently associated with worse survival were: group 2, age > 70 years and stage at the moment of diagnosis. CONCLUSIONS: The use of FIT as a diagnostic strategy in symptomatic patients may improve survival in CRC. Nonetheless,FIT is still not widely used in our region.

Predictors of Adherence to Continuous Positive Airway Pressure in Older Adults With Apnea and Amnestic Mild Cognitive Impairment.

BACKGROUND: Almost 60% of adults with amnestic mild cognitive impairment (aMCI) have obstructive sleep apnea (OSA). Treatment with continuous positive airway pressure (CPAP) may delay cognitive decline, but CPAP adherence is often suboptimal. In this study, we report predictors of CPAP adherence in older adults with aMCI who have increased odds of progressing to dementia, particularly due to Alzheimer's disease. METHODS: The data are from Memories 2, "Changing the Trajectory of Mild Cognitive Impairment with CPAP Treatment of Obstructive Sleep Apnea." Participants had moderate to severe OSA, were CPAP naïve, and received a telehealth CPAP adherence intervention. Linear and logistic regression models examined predictors. RESULTS: The 174 participants (mean age 67.08 years, 80 female, 38 Black persons) had a mean apnea-hypopnea index of 34.78, and 73.6% were adherent, defined as an average of ≥4 hours of CPAP use per night. Only 18 (47.4%) Black persons were CPAP adherent. In linear models, White race, moderate OSA, and participation in the tailored CPAP adherence intervention were significantly associated with higher CPAP use at 3 months. In logistic models, White persons had 9.94 times the odds of adhering to CPAP compared to Black persons. Age, sex, ethnicity, education, body mass index, nighttime sleep duration, daytime sleepiness, and cognitive status were not significant predictors. CONCLUSIONS: Older patients with aMCI have high CPAP adherence, suggesting that age and cognitive impairment should not be a barrier to prescribing CPAP. Research is needed to improve adherence in Black patients, perhaps through culturally tailored interventions.

Colorectal Cancer Survival in 50- to 69-Year-Olds after Introducing the Faecal Immunochemical Test.

Population screening has improved early diagnosis of colorectal cancer (CRC). Nonetheless, most cases are diagnosed in symptomatic patients. Faecal immunochemical testing has been recommended for assessing patients with lower gastrointestinal symptoms, but whether it improves patient survival is unknown. Our objective was to compare CRC survival in 50- to 69-year-olds between asymptomatic screen-detected patients and symptomatic patients by route to diagnosis. METHODS: We identified all cases of CRC diagnosed in 50-to 69-year-olds between 2009 and 2016, in Donostialdea (Gipuzkoa, Spain). Three groups were created: 1-screen-detected CRC; 2-CRC detected in symptomatic patients after a positive faecal immunochemical test(FIT); and 3-CRC detected in symptomatic patients without a FIT or after a negative result. We analysed survival using the Kaplan-Meier method and log-rank tests. RESULTS: Of 930 patients diagnosed with CRC, 433 cases were detected through screening and 497 in symptomatic patients, 7.9% after a positive FIT and 45.5% by other means. The 3-year CRC survival was significantly lower in group 3 (69.5%) than groups 1 (93%; p = 0.007) or 2 (87.5%; p = 0.02). The risk of death was lower in groups 1 (HR 0.42, 95% CI 0.30-0.58) and 2 (HR 0.51; 95% CI 0.29-0.87). CONCLUSION: Half of CRC cases in 50- to 69-year-olds are diagnosed outside screening. Use of the FIT as a diagnostic strategy in symptomatic patients may improve survival.

Polysaccharide-based films for the prevention of unwanted postoperative adhesions at biological interfaces.

Postoperative adhesions protect, repair, and supply nutrients to injured tissues; however, such adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated. An ideal adhesion barrier should not only effectively prevent unwanted adhesions but should be easy to use, however, those that are currently available have inconsistent efficacy and are difficult to handle or to apply. A robust hydrogel film composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized hyaluronic acid (GMHA)) represents a solution to this problem. A sacrificial porogen (urea) was used in the film manufacture process to impart macropores that yield films that are more malleable and tougher than equivalent films produced without the sacrificial porogen. The robust mechanical behavior of these templated alginate/GMHA films directly facilitated handling characteristics of the barrier film. In a rat peritoneal abrasion model for adhesion formation, the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®. STATEMENT OF SIGNIFICANCE: Postoperative adhesions often remain permanent and complicate otherwise successful surgeries by tethering tissues together that are normally separated and pose potentially significant challenges to patients. Therefore, the generation of adhesion barriers that are easy to deploy during surgery and effectively prevent unwanted adhesions is a big challenge. In this study robust hydrogel films composed of alginate and a photo-crosslinkable hyaluronic acid (HA) derivative (glycidyl methacrylate functionalized HA, GMHA) were fabricated and investigated for their potential to act as a solution to this problem using a rat peritoneal abrasion model for adhesion formation. We observed the polysaccharide films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion technology on the market, Seprafilm®, suggesting that such films represent a promising strategy for the prevention of postoperative adhesions.

The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue.

Age-related macular degeneration (AMD) is a common cause of central visual loss in the elderly. Retinal pigment epithelial (RPE) cell loss occurs early in the course of AMD and RPE cell transplantation holds promise to slow disease progression. We report that subretinal transplantation of RPE stem cell (RPESC)-derived RPE cells (RPESC-RPE) preserved vision in a rat model of RPE cell dysfunction. Importantly, the stage of differentiation that RPESC-RPE acquired prior to transplantation influenced the efficacy of vision rescue. Whereas cells at all stages of differentiation tested rescued photoreceptor layer morphology, an intermediate stage of RPESC-RPE differentiation obtained after 4 weeks of culture was more consistent at vision rescue than progeny that were differentiated for 2 weeks or 8 weeks of culture. Our results indicate that the developmental stage of RPESC-RPE significantly influences the efficacy of RPE cell replacement, which affects the therapeutic application of these cells for AMD.

Human RPE Stem Cell-Derived RPE Preserves Photoreceptors in the Royal College of Surgeons Rat: Method for Quantifying the Area of Photoreceptor Sparing.

PURPOSE: Numerous preclinical studies have shown that transplantation of stem cell-derived retinal pigment epithelial cell (RPE) preserves photoreceptor cell anatomy in the dystrophic Royal College of Surgeons (RCS) rat. How rescue is spatially distributed over the eye, relative to the transplantation site, is less clear. To understand spatial variations in transplant efficacy, we have developed a method to measure the spatial distribution of rescued photoreceptor cells. METHODS: Human RPE Stem Cell-derived RPE (RPESC-RPE) cells were subretinally injected into RCS rat eyes. After tissue recovery and orientating the globe, a series of retinal sections were cut through the injected area. Sections were stained with DAPI (4',6-diamidino-2-phenylindole) and a number of photoreceptor nuclei were counted across the nasal-temporal and superior-inferior axes. These data were used to construct 2D maps of the area of photoreceptor cell saving. RESULTS: Photoreceptor cell preservation was detected in the injected temporal hemisphere and occupied areas greater than 4 mm(2) centered near the injection sites. Rescue was directed toward the central retina and superior and inferior poles, with maximal number of rescued photoreceptor cells proximal to the injection sites. CONCLUSIONS: RPESC-RPE transplantation preserves RCS photoreceptor cells. The photoreceptor cell contour maps readily convey the extent of rescue across the eye. The consistent alignment and quantification of results using this method allow the application of other downstream statistical analyses and comparisons to better understand transplantation therapy in the eye.

Patient-Specific Modeling of Heart Valves: From Image to Simulation.

Heart valves play a very important role in the functioning of the heart and many of the heart failures are related to the valvular dysfunctions, e.g. aortic stenosis and mitral regurgitation. As the medical field is moving towards a patient-specific diagnosis and treatment procedures, modeling of heart valves with patient-specific information is becoming a significant tool in medical field. Here we present the ingredients for valve simulation specifically the aortic valve, with a main focus on a novel spline-based mapping technique which solves many issues in generating patient-specific models - the microstructural mapping, the pre-strain calculations, prescribing dynamic boundary conditions, validation and inverse-modeling to obtain material parameters.