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Degenerative retinal disease leads to significant visual morbidity worldwide. Diabetic retinopathy and macular degeneration are leading causes of blindness in the developed world. While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions. Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery. This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies. These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration. Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas. Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.

Objectives Cholelithiasis and cholecystitis are common conditions that frequently require patients to come to the Emergency Department (ED) and undergo diagnostic imaging. The purpose of this study was to evaluate the test characteristics of emergency physician performed point-of-care ultrasound (POCUS) to diagnose cholelithiasis and cholecystitis in a Canadian ED. Methods A health records review was performed on all ED patients > 17 years of age for whom POCUS was performed to diagnose cholelithiasis and cholecystitis in a Canadian academic ED over a 5-year period. The sensitivity, specificity, predictive values, and likelihood ratios were calculated. The gold standard used for diagnosis was pathology, laparoscopy, radiology-performed comprehensive ultrasonography, followed by computed tomography scans. Results A total of 577 patients were included in the study. The sensitivity and specificity of POCUS to diagnose cholelithiasis was 95.2% (95% CI 91.1-97.8%) and 93.1% (95% CI 90.1-95.4%). The positive and negative likelihood ratios for POCUS to diagnose cholelithiasis were found to be 14 and 0.05; the negative predictive value was 97.6% (95% CI 95.5-98.7%). The sensitivity and specificity of POCUS to diagnose cholecystitis was 67.1% (95% CI 54.9-77.9%) and 97.6% (95% CI 95.9-98.8%). The positive and negative likelihood ratios for POCUS to diagnose cholecystitis were found to be 28 and 0.34; the negative predictive value was 95.6% (95% CI 93.9-96.8%). Conclusion POCUS is reliable for the diagnosis of cholelithiasis and for ruling in cholecystitis. In cases where POCUS is negative or indeterminate for cholecystitis, further imaging should be obtained as clinical suspicion warrants. Keywords Retrospective • Point-of-care ultrasound • Cholelithiasis • Cholecystitis RésuméObjectifs La cholélithiase et la cholécystite sont des troubles médicaux courants qui obligent fréquemment les patients à se rendre aux urgences et subir une imagerie diagnostique. Le but de cette étude était d'évaluer les caractéristiques des tests de l'échographie au point d'intervention (POCUS) effectuée par des médecins urgentistes pour diagnostiquer la cholélithiase et la cholécystite dans une urgence canadienne.

Background Comorbidity burden is associated with development of cancer, stage at diagnosis, and treatment outcomes. We evaluated the association between comorbidity burden, receipt of adjuvant immunotherapy, and survival in patients with stage III melanoma. Methods Using the National Cancer Database, we identified 16,906 patients with stage III melanoma who underwent surgery of the primary site. Outcomes included receipt of adjuvant immunotherapy and overall survival; independent variables included Charlson/ Deyo comorbidity index (CDI) and receipt of adjuvant immunotherapy. Results Patients with CDI scores of two or more averaged 30.0% and 30.9% lower adjusted odds of receiving adjuvant immunotherapy relative to patients with a CDI score of zero or one, respectively (P = 0.001 and 0.002, respectively). Longer survival was associated with lower CDI scores (all P < 0.001) and receipt of adjuvant immunotherapy (P < 0.001). Patients who received adjuvant immunotherapy averaged 16.0% lower adjusted risk of death compared to patients who did not (P < 0.001), which was constant within all CDI cohorts. Patients with a CDI score of two or more averaged 53.4% and 39.1% higher adjusted risk of death relative to patients with a CDI score of zero or one (both P < 0.001). Conclusion Greater comorbidity burden was associated with lower receipt of adjuvant immunotherapy; however, adjuvant immunotherapy provided similar survival benefit for patients' irrespective comorbidity burden. Our findings suggest that patients with stage III melanoma who have a greater comorbidity burden may benefit from adjuvant immunotherapy but should not replace careful patient selection by the clinician.

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