Throughout the gastrointestinal (GI) tract, a distinct mucus layer composed of highly glycosylated proteins called mucins plays an essential role in providing lubrication for the passage of food, participating in cell signaling pathways and protecting the host epithelium from commensal microorganisms and invading pathogens, as well as toxins and other environmental irritants. These mucins can be broadly classified into either secreted gel-forming mucins, those that provide the structural backbone for the mucus barrier, or transmembrane mucins, those that form the glycocalyx layer covering the underlying epithelial cells. Goblet cells dispersed among the intestinal epithelial cells are chiefly responsible for the synthesis and secretion of mucins within the gut and are heavily influenced by interactions with the immune system. Evidence from both clinical and animal studies have indicated that several GI conditions, including inflammatory bowel disease (IBD), colorectal cancer, and numerous enteric infections are accompanied by considerable changes in mucin quality and quantity. These changes include, but are not limited to, impaired goblet cell function, synthesis dysregulation, and altered post-translational modifications. The current review aims to highlight the structural and functional features as well as the production and immunological regulation of mucins and the impact these key elements have within the context of barrier function and host defense in intestinal inflammation.
Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina. Recent reports have highlighted the potential role of mucosal surface microbes in the pathogenesis of AMD. in this case-control study, the composition of the nasal and oral microbiota in newly diagnosed neovascular age-related macular degeneration cases (6 male, 7 female) was compared to controls without retinal diseases (2 male, 3 female). PCR amplification of 16S rRNA genes was performed with universal primers amplifying the V4 variable region (515F-806R). Distinct microbial community characterization was achieved using principal coordinates Analysis (pcoA) of the Bray-curtis index with comparative analysis between cases and controls performed within QIIME 2. Sequencing of all cases and controls revealed clear separation with strong beta diversity between oral and nasal microbial communities (p < 0.001). Microbial composition differed between cases and controls in both oral and nasal samples. The top three oral microbes identified as different compared to controls included Burkholderiales (7.41 log2fold change, p = 3.29E-05), Actinomyceataceae (6.22 log2fold change, p = 3.73E-06) and Gemella (5.28 log2fold change, p = 0.0002). The top three nasal microbes identified as different compared to controls included Rothia (13.6 log2fold change, p = 3.63E-18), Actinobacteria (10.29 log2fold change, p = 9.81E-10) and Propionibacteriales (8.73 log2fold change, p = 6.74E-09). These relative shifts in communities of bacteria detected in newly diagnosed neovascular AMD patients may suggest additional mechanistic links in disease pathogenesis.
Purpose: To describe a case of proliferative retinopathy as the presenting manifestation of chronic myeloid leukemia in a patient with poorly controlled diabetes mellitus (DM). Undiagnosed chronic myeloid leukemia in a patient with pre-existing poorly controlled DM is rarely encountered but must be recognized to treat appropriately with systemic chemotherapy. Significant fundus finding overlaps with DM making the recognition of chronic myeloid leukemia challenging.Methods: Case report.Results: Fundoscopy revealed scattered dot-blot hemorrhages, venous beading, and numerous Roth spots in all quadrants, in both eyes. In the right eye, there was also a vitreous hemorrhage with evidence of neovascularization near the inferior arcade. Intravenous fluorescein angiography showed significant peripheral capillary nonperfusion without evidence of exudation in both eyes. No macular edema was observed on optical coherence tomography. A review of systems and physical examination was negative for constitutional symptoms, lymphadenopathy, organomegaly, and other symptoms. Retinal findings prompted a complete blood count, which revealed significant leukocytosis. A bone marrow biopsy confirmed a diagnosis of chronic myeloid leukemia. Systemic chemotherapy and pan-retinal photocoagulation successfully normalized the leukocyte count and resolved the vitreous hemorrhage and neovascularization. Conclusion:The presence of numerous Roth spots in all quadrants, extensive areas of capillary nonperfusion on intravenous fluorescein angiography, and neovascularization in the absence of exudation or macular edema should prompt investigations to rule out hematologic disorders.
BACKGROUND Positive family history is a risk factor for development of colorectal cancer. Despite numerous studies on the topic, the absolute risk in patients with a positive family history remains unclear and therefore studies are lacking to validate non-invasive screening methods in individuals with positive family history. AIM To quantify the risk of colorectal cancer in individuals with a positive family history. METHODS A comprehensive electronic literature search was performed using PubMed from January 1955 until November 2017, EMBASE from 1947 until 2018, and Cochrane Library without date restrictions. Two independent reviewers conducted study selection, data extraction and quality assessment. A meta-analysis of Mantel-Haenzel relative risks was performed using the random effects model. Newcastle-Ottawa scale was used to score the quality of selected papers. Funnel plot and Egger’s regression test was performed to detect publication bias. Subgroup analysis was performed comparing Asian and non-Asian studies. Sensitivity analyses were performed to rule out the effect of the timing of the study, overall quality, the main outcome and the effect of each individual study in overall result. RESULTS Forty-six out of 3390 studies, including 906981 patients were included in the final analysis. 41 of the included studies were case-control and 5 were cohort. A positive family history of colorectal cancer in first-degree relatives was associated with significantly increased risk of colorectal cancer with a relative risk of 1.87 (95%CI: 1.68-2.09; P < 0.00001). Cochrane Q test was significant ( P < 0.00001, I 2 = 90%). Egger’s regression test showed asymmetry in the funnel plot and therefore the Trim and Fill method was used which confirmed the validity of the results. There was no difference between Asian versus non-Asian studies. Results remained robust in sensitivity analyses. CONCLUSION Individuals with a positive family history of colorectal cancer are 1.87 times more likely to develop colorectal cancer. Screening guidelines should pay specific attention to individuals with positive family history and further studies need to be done on validating current screening methods or developing new modalities in this high-risk population.
ObjectiveTo evaluate the diagnostic accuracy of teleretinal screening compared with face-to-face examination for detection of diabetic retinopathy (DR) and age-related macular degeneration (AMD).Methods and analysisThis study adhered to the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA). A comprehensive search of OVID MEDLINE, EMBASE and Cochrane CENTRAL was performed from January 2010 to July 2021. QUADAS-2 tool was used to assess methodological quality and applicability of the studies. A bivariate random effects model was used to perform the meta-analysis. Referrable DR was defined as any disease severity equal to or worse than moderate non-proliferative DR or diabetic macular oedema (DMO).Results28 articles were included. Teleretinal screening achieved a sensitivity of 0.91 (95% CI: 0.82 to 0.96) and specificity of 0.88 (0.74 to 0.95) for any DR (13 studies, n=7207, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) low). Accuracy for referrable DR (10 studies, n=6373, GRADE moderate) was lower with a sensitivity of 0.88 (0.81 to 0.93) and specificity of 0.86 (0.79 to 0.90). After exclusion of ungradable images, the specificity for referrable DR increased to 0.95 (0.90 to 0.98), while the sensitivity remained nearly unchanged at 0.85 (0.76 to 0.91). Teleretinal screening achieved a sensitivity of 0.71 (0.49 to 0.86) and specificity of 0.88 (0.85 to 0.90) for detection of AMD (three studies, n=697, GRADE low).ConclusionTeleretinal screening is highly accurate for detecting any DR and DR warranting referral. Data for AMD screening is promising but warrants further investigation.PROSPERO registration numberCRD42020191994.
Purpose: To compare the visual outcomes after prompt pars plana vitrectomy (PPV) with tap biopsy and intravitreal antimicrobial injection to treat postinjection and postsurgery endophthalmitis.Methods: The Cochrane Central Register of Controlled Trials, Ovid MEDLINE, and Ovid Embase databases were searched for articles published between January 2010 and November 2020. Two independent reviewers selected articles and extracted data. We analyzed data in RevMan 5.3 and assessed methodological quality using the Cochrane ROBINS-I tool. The mean improvement in visual outcome was compared between PPV and intravitreal antimicrobial injection as a relative risk of improving $2 lines and a mean logarithm of the minimal angle of resolution difference in improvement.Results: Fifteen retrospective case series (1,355 eyes), of which 739 eyes (55%) received intravitreal antimicrobial injection and 616 (45%) received PPV as initial treatment, were included. The overall relative risk of improving 2 or more lines in PPV in comparison with intravitreal antimicrobial injection was 1.04 (95% CI 0.88-1.23; P = 0.61; I 2 = 0%) with a mean difference of 0.04 (95% CI 20.18 to 0.27; P = 0.69; I 2 = 0%). The results stayed robust when subgroup analysis based on causative procedure for endophthalmitis was performed.Conclusion: Intravitreal antimicrobial injection is noninferior to PPV for the treatment of postcataract operation, postinjection, and post-PPV endophthalmitis.
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