Head-to-Head Diagnostic Test Accuracy Meta-analysis of Colonoscopy and Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia.

Background: Studies on the use of fecal immunochemical test (FIT) in colorectal screening have long assumed perfect accuracy for colonoscopy. No study to date has directly compared the diagnostic accuracy of colonoscopy and FIT to detect advanced neoplasia (AN) in a head-to-head diagnostic accuracy meta-analysis. Methods: A comprehensive electronic search was performed for a head-to-head comparison of FIT and colonoscopy using a third acceptable reference standard in asymptomatic adults. Cochrane methodology was used to perform a head-to-head diagnostic test accuracy (DTA) meta-analysis. Quality assessment tool for diagnostic accuracy studies-2 (QUADAS-2) was used to assess the risk of bias in included studies. Results: Two studies met the eligibility criteria. Overall sensitivity and specificity were 98.5 (95% CI 96.3-100%) and 100% (99.9-100%) for colonoscopy and 16.4% (10.3-22.6%) and 95.4% (94.3-96.4%) for FIT. Colonoscopy was significantly better than FIT (P < 0.0001). The positive and negative likelihood ratios (LRs) were 1.75 (1.57-1.96) and 0.03 (0.01-0.08) for colonoscopy and 3.02 (2.01-4.55) and 0.88 (0.82-0.95) for FIT, respectively. Conclusion: Colonoscopy provides significantly better diagnostic accuracy to detect AN compared with FIT (GRADE: ⨁⨁◯◯). Our study provided precise sensitivity and specificity of both colonoscopy and FIT and a revision in screening policies based on an updated cost-effectiveness analysis considering the results of the head-to-head analysis.

ATYPICAL PROLIFERATIVE RETINOPATHY AS THE PRESENTING FEATURE OF CHRONIC MYELOID LEUKEMIA IN A PATIENT WITH DIABETES MELLITUS.

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.

Diagnostic accuracy of teleretinal screening for detection of diabetic retinopathy and age-related macular degeneration: a systematic review and meta-analysis.

OBJECTIVE: To 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 ANALYSIS: This 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). RESULTS: 28 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). CONCLUSION: Teleretinal screening is highly accurate for detecting any DR and DR warranting referral. Data for AMD screening is promising but warrants further investigation. PROSPERO REGISTRATION NUMBER: CRD42020191994.

Potential Modifiers and Different Cut-offs in Diagnostic Accuracy of Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia: A Diagnostic Test Accuracy Meta-analysis.

Background: Fecal immunoglobulin test (FIT) has been advocated as the first line of screening for colorectal cancer (CRC) in several jurisdictions. Most studies have focused on CRC as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different thresholds of FIT as compared with colonoscopy for detection of advanced colonic neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as the reference standard to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy (DTA) meta-analysis. Diagnostic accuracy of different cut-offs of FIT, including 25, 50, 75, 100, 150, and 200 ng/mL, were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers, including age, location of the tumor, and time from FIT to colonoscopy. Results: Twenty-four studies were included with no evidence of publication bias. The sensitivity of FIT did not decrease with lowering the cut-off, although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL, and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. Diagnostic accuracy of FIT did not significantly differ in proximal versus distal lesions or in individuals below or over the age of 50 years. The results remained robust in a meta-regression of the location of the study, time from FIT to colonoscopy, and methodological quality. Conclusion: The sensitivity of FIT might have been overestimated in previous studies focusing on CRC, and it seems to be independent of age, location of neoplasia, or cut-offs, contrary to some previous studies. Lowering the cut-off will reduce the diagnostic odds ratio (DOR) by increasing specificity but without any effect on sensitivity.

Massive Spontaneous Suprachoroidal Hemorrhage in a Patient With Type 1 Chronic Myeloid Leukemia and Lymphoplasmacytic Lymphoma: Case Report and Review of the Literature.

Purpose: This work reports a rare case of spontaneous suprachoroidal hemorrhage (SSCH) and summarizes the literature on its treatment options and outcomes. Methods: A case report and comprehensive literature review are presented on the medical and surgical management of SSCH on PubMed from 1998 to 2021. Results: The literature search revealed 58 studies, 33 of which included 52 eyes of 47 patients. Surgical treatment typically consisted of choroidal drainage with posterior sclerotomies combined with pars plana vitrectomy and silicone oil placement. Medical therapy involved intraocular pressure control with laser peripheral iridotomy and topical, oral, and intravenous medication. Conclusions: In cases of SSCH, conservative management and a prompt workup should be initiated to identify the cause before proceeding with surgery. If the initial workup does not reveal a cause, medical and surgical treatments are both viable and the decision is at the discretion of the treating physician.

Recurrent Uveitis Related to Ibrutinib for Treatment of Chronic Lymphocytic Leukemia.

PURPOSE: We describe a case vision-threatening sclerouveitis as a probable adverse drug reaction to ibrutinib. METHODS: Case report. RESULTS: Ibrutinib is an inhibitor of Bruton's kinase which has shown success in the treatment of hematological malignancies such as chronic lymphocytic leukemia. Despite being generally well tolerated, recent studies have implicated ibrutinib in several adverse events affecting organs such as the heart, intestines, and the eyes. We present the case of a patient who developed severe sclerouveitis after approximately one year of ibrutinib therapy, and suggest this is a probable adverse drug reaction associated with ibrutinib in accordance with the Naranjo algorithm, highlighting the importance of prompt management of ocular symptoms in these patients.

Intraocular calcidiol: Uncovering a role for vitamin D in the eye.

Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease. METHODS: 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D3-generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease. RESULTS: 25(OH)D3 was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D3 concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D3 did not correlate with serum levels of 25(OH)D3. There was no difference between the level of 25(OH)D3 measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001). CONCLUSIONS: Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis.

Quantitative risk of positive family history in developing colorectal cancer: A meta-analysis.

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.