Adipokine (adiponectin-rs1501299) Gene Variant and Patient Characteristics in Relation to Metabolic-associated Fatty Liver Disease.

Background: Several genetic and metabolic variables, most notably the variation in the adipokine gene rs1501298, have been linked to metabolic-associated fatty liver disease etiopathogenesis (MAFLD). Liver biopsy, the gold standard for diagnosing MAFLD, is an invasive procedure; therefore, alternative diagnostic methods are required. Consequently, the integration of these metabolic variables with some of the patients' characteristics may facilitate the development of noninvasive diagnostic methods that aid in the early detection of MAFLD, identification of at-risk individuals and planning of management strategies. Methods: This study included 224 Egyptians (107 healthy individuals and 117 MAFLD patients). Age, sex, BMI, clinical and laboratory characteristics, and rs1501299 adipokine gene polymorphisms were examined. The rs1501299 variant, insulin resistance, hypertension, obesity, blood pressure, lipid profile, hemoglobin A1C level, and hepatic fibrosis predictors were evaluated for MAFLD risk. The feasibility and effectiveness of developing non-invasive MAFLD diagnostic models will be investigated. Results: The +276G/T (rs1501299) polymorphism (GG vs GT/TT) was linked with MAFLD (OR: 0.43, CI: 0.26-0.69, P = 0.002). The GG variants had lower MAFLD rates than those of the GT and TT variants. In addition to altered lipid profiles, patients with MAFLD showed increased gamma-glutamyl transferase levels (GGT: 56 IU/L vs. 36 IU/L). Genetic diversity also affects the accuracy of hepatic fibrosis and steatosis prediction. Hepatic fibrosis and steatosis predictors had receiver operating characteristic (ROC) AUCs of 0.529%, 0.846%, and 0.700-0.825%, respectively. We examined a diagnostic model based on these variables and demonstrated its effectiveness. Conclusion: The Adipokine variant rs1501299 increased the risk of MAFLD. Identifying and genotyping this variation and other metabolic variables allow for a noninvasive diagnostic model for early MAFLD diagnosis and identification of those at risk. This study illuminates the prevention and management of MAFLD. Further research with more participants is needed to verify these models and to prove their MAFLD diagnostic efficacy.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

AIM: This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. METHODS: The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. RESULTS: Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. CONCLUSION: The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

Clinical Outcomes Following Implementation of a Formalized "Flashes and Floaters" Emergency Department Triage Protocol.

PURPOSE: To report outcomes of patients presenting to the emergency department (ED) with new-onset visual flashes and/or floaters following implementation of a formalized triage protocol allowing eligible patients to be discharged for prompt outpatient ophthalmic examination. DESIGN: Retrospective consecutive case series. METHODS: Patient characteristics, protocol eligibility, and clinical outcomes were recorded for adult patients triaged within a formal "flashes and floaters" protocol at a single academic ED. RESULTS: A total of 457 patients presented for 471 unique ED encounters with a chief complaint of visual flashes and/or floaters between October 2014 and May 2018. In all, 61% of patient encounters (287/471) met protocol criteria for prompt outpatient ophthalmic examination, of whom 94% (269/287) were examined within 48 hours. Final diagnoses of protocol-eligible patients were posterior vitreous detachment only (73%, 197/269), retinal break(s) (10%, 26/269), migraine (5%, 14/269), and no cause or new cause found (10%, 27/269). No protocol-eligible patients had retinal detachment or diagnoses requiring emergent diagnostic or therapeutic care (0%, 95% CI = 0%-1.1%). Final diagnoses following 175 encounters not meeting criteria for deferred examination included posterior vitreous detachment only (25%, 43/175), retinal break(s) (19%, 33/175), macula-involving retinal detachment (13%, 22/175), macula-sparing retinal detachment (11%, 19/175), retinal arterial occlusion (2%, 3/175), and stroke (0.6%, 1/175). The Cohen kappa for agreement on protocol eligibility between the ED physician and ophthalmologist was 0.85. CONCLUSIONS: A formalized ED "flashes and floaters" triage protocol may help identify patients for whom prompt outpatient ophthalmic examination may be more safely considered.

Epitope-Based Peptide Vaccine Design against Fructose Bisphosphate Aldolase of Candida glabrata: An Immunoinformatics Approach.

BACKGROUND: Candida glabrata is a human opportunistic pathogen that can cause life-threatening systemic infections. Although there are multiple effective vaccines against fungal infections and some of these vaccines are engaged in different stages of clinical trials, none of them have yet been approved by the FDA. AIM: Using immunoinformatics approach to predict the most conserved and immunogenic B- and T-cell epitopes from the fructose bisphosphate aldolase (Fba1) protein of C. glabrata. Material and Method. 13 C. glabrata fructose bisphosphate aldolase protein sequences (361 amino acids) were retrieved from NCBI and presented in several tools on the IEDB server for prediction of the most promising epitopes. Homology modeling and molecular docking were performed. RESULT: The promising B-cell epitopes were AYFKEH, VDKESLYTK, and HVDKESLYTK, while the promising peptides which have high affinity to MHC I binding were AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL, and YFKEHGEPL. Two peptides, LFSSHMLDL and YIRSIAPAY, were noted to have the highest affinity to MHC class II that interact with 9 alleles. The molecular docking revealed that the epitopes QTSNGGAAY and LFSSHMLDL have the lowest binding energy to MHC molecules. CONCLUSION: The epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines in that they are more specific, less time consuming, safe, less allergic, and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidate's epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cell epitopes from the Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine against C. glabrata.

Population-Based Incidence of Optic Neuritis in the Era of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies.

PURPOSE: To re-evaluate the population-based incidence of optic neuritis in the era of aquaporin-4-immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which are biomarkers of optic neuritis that is distinct from multiple sclerosis (MS). Over the past 15 years, 2 new biomarkers have been discovered that allow for further characterization of the cause of atypical optic neuritis: AQP4-IgG and MOG-IgG. DESIGN: Retrospective, population-based cohort. SETTING: population-based. PARTICIPANTS: all residents of Olmsted County, Minnesota, with optic neuritis diagnosed between January 1, 2000, and December 31, 2018. METHODS: The Rochester Epidemiology Project database was used to identify patients. Sera were tested for AQP4-IgG and MOG-IgG by using a live-cell-based flow cytometry assay. Main outcome measurements were the incidence and cause of optic neuritis. RESULTS: Optic neuritis was diagnosed in 110 patients, providing an annual incidence of 3.9 per 100,000. The final diagnosis was MS in 57%, idiopathic in 29%, MOG-IgG-associated disorder in 5%, AQP4-IgG-seropositive neuromyelitis optic spectrum disorder (NMOSD) in 3%, infectious type in 2%, sarcoidosis in 2%, seronegative NMOSD in 1%, and medication-related in 1%. All 3 patients positive for AQP4-IgG had more than 1 optic neuritis attack, 2 with residual no light perception vision in at least 1 eye. Among MOG-IgG-positive patients, 4 of 6 patients had recurrent optic neuritis, and all 6 had a final visual acuity of 20/30 or better. CONCLUSIONS: At a population level, AQP4-IgG and MOG-IgG account for 9% of optic neuritis and are associated with recurrent attacks, but MOG-IgG optic neuritis has a better visual outcome than AQP4-IgG optic neuritis.

Immediate Postoperative Alignment Following Bimedial Rectus Recession for Esotropia in Children Compared to Adults.

PURPOSE: To determine whether the immediate postoperative alignment among patients undergoing successful bilateral weakening surgery for esotropia is different in children compared to adults. METHODS: The medical records of all patients undergoing surgery for esotropia by a single surgeon at a major academic referral center between January 1, 2002, and July 1, 2014 (n = 544), were retrospectively reviewed. Exclusion criteria included those with prior strabismus surgery, unilateral surgery, strengthening procedures, vertical or superior oblique surgery, and those wearing hyperopic spectacles for accommodative esotropia. Additionally, all patients had to have a 1- and 6-week postoperative examination and 8 prism diopters (PD) or less of deviation at their 6-week examination. RESULTS: Ninety-five (17.5%) of the 544 patients met the inclusion criteria. Surgery was performed at a median age of 3.7 years (range: 7 months to 86 years) for a median esodeviation of 35 PD (range: 12 to 70 PD). Among the 73 patients younger than 11 years, the immediate mean postoperative alignment was 9 PD of exotropia (range: 14 PD esotropia to 30 PD exotropia) compared to 2 PD of exotropia (range: 9 PD esotropia to 30 PD exotropia) in the 22 patients 11 years or older (P = .001). Seventy-one percent of successfully aligned patients younger than 11 years were exotropic in the immediate postoperative week compared to 23% of those 11 years or older (P < .001). Twenty-four (32.8%) of the younger cohort had an immediate overcorrection of 15 PD or more compared to 1 (4.5%) in the older cohort (P = .006). CONCLUSIONS: Successful bilateral strabismus surgery for children with esotropia results in a significantly greater overcorrection, compared to adults, in the immediate postoperative period. [J Pediatr Ophthalmol Strabismus. 2018;55(5):299-305.].

Prevalence of Mental Health Illness among Patients with Adult-Onset Strabismus.

BACKGROUND: Children diagnosed with some forms of strabismus were recently found to have an increased risk of developing mental illness by early adulthood. The purpose of this case-controlled study was to determine if adults with non-paralytic forms of strabismus are similarly at an elevated risk for developing mental illness. METHODS: The medical records of all patients diagnosed as adults (≥ 19 years of age) with convergence insufficiency (CI) (n = 118), divergence insufficiency (DI) (n = 80), and small angle hypertropia (HT (n = 99) from January 1, 1985, through December 31, 2004, were retrospectively reviewed. Each case was compared with a sex- and birth date-matched non-strabismic control. The medical records were reviewed for mental health diagnoses, including inpatient and outpatient encounters, psychiatric ER visits, and medication use. RESULTS: Mental health disorders were diagnosed in 65 (55.1%) patients with CI compared to 54 (45.8%) controls (p = 0.15), in 51 (63.8%) patients with DI compared to 42 (52.5%) controls (p = 0.15), and in 63 (63.6%) patients with HT compared to 57 (57.6%) controls (p = 0.38). CI patients were not more likely to have mental health disorders than their controls (p = 0.15). Mental health hospitalizations (p = 0.02), psychiatric medication use (p = 0.04), and unspecified anxiety disorders (p = 0.03) were higher in DI patients compared to controls. HT patients were found to have more generalized anxiety disorders (p = 0.003) than controls. CONCLUSIONS: Adults with some forms of strabismus (DI and HT) appear to have an increased risk of mental illness and its comorbidities, compared to age- and gender-matched non-strabismic controls.

Trabeculectomy-related complications in Olmsted County, Minnesota, 1985 through 2010.

IMPORTANCE: Trabeculectomy is the surgical standard of care for patients with medically refractory glaucoma. The use of antimetabolite agents, such as mitomycin, has increased the rate of complications after trabeculectomy. OBJECTIVE: To determine the rate of trabeculectomy-related complications during a 25-year study. DESIGN, SETTING, AND PARTICIPANTS: For this retrospective, population-based study, we enrolled the residents of Olmsted County, Minnesota, who underwent a trabeculectomy from January 1, 1985, through December 31, 2010, at the Mayo Clinic and Olmsted Community Hospital. Data were collected from August 2012 to September 2013 followed by data analysis through January 2014. EXPOSURES: After reviewing the patient records, we determined the occurrence of complications, including bleb leak, hypotony, hyphema, choroidal effusion, choroidal hemorrhage, blebitis, and endophthalmitis, as they relate to the mitomycin concentration administered during the operation. We reviewed relevant publications in Ovid, MEDLINE, and PubMed to identify studies representative of the reported trabeculectomy complication rate. MAIN OUTCOMES AND MEASURES: Cumulative probabilities of short- and long-term complications, determined using the Kaplan-Meier method, and the relation to mitomycin concentration applied during trabeculectomy. RESULTS: In 334 patients, 460 eyes underwent trabeculectomy (mean [SD; range] follow-up, 7.7 [5.7; 0-27.7] years). Among them, 159 eyes had complications, with early complications (<3 months) in 100 eyes and late complications (≥3 months) in 59 eyes during the follow-up. Ten eyes had an early and a late complication. The 20-year cumulative chances of early, late, or any complication were 19.7% (95% CI, 16.2%-23.6%), 26.0% (95% CI, 15.0%-36.0%), and 45.0% (95% CI, 38.0%-52.0%), respectively. The cumulative probabilities of vision-threatening complications during 20 years were 2.0% (95% CI, 0%-4.0%) for blebitis and 5.0% (95% CI, 1.0%-9.0%) for endophthalmitis. Association between the rate of trabeculectomy complications and mitomycin dose used was P = .77. In total, 98 cases (21.3%) underwent further surgical procedures related directly to the complication. CONCLUSIONS AND RELEVANCE: The rate of trabeculectomy-related complications does not appear to be associated with mitomycin use during a mean follow-up of 7.7 years. The rate of vision-threatening complications appears to be comparable to those of previous studies of shorter duration.

Tourniquets and occlusion: the pressure of design.

UNLABELLED: Nerve injuries result from tourniquet pressure. The objective was to determine arterial occlusion and completion pressures with the 3.8-cm-wide windlass Combat Application Tourniquet (CAT) and the 10.4-cm-wide Stretch, Wrap, and Tuck Tourniquet (SWAT-T). METHODS: Sixteen volunteers self-applied and had tourniquets applied to their thighs and arms (CAT and SWAT-T, random order, then blood pressure cuffs). RESULTS: Occlusion (Doppler signal elimination) pressures were higher than predicted (p < 0.0001), highest with the CAT (p < 0.0001), and often lower than completion pressures (completion median, range: CAT 360, 147-745 mm Hg; SWAT-T 290, 136-449 mm Hg; cuff 184, 108-281 mm Hg). Three CAT thigh and 9 CAT arm completion pressures were >500 mm Hg. Pressure decreases and occlusion losses occurred over 1 minute (pressure decrease: CAT 44 ± 33 mm Hg; SWAT-T 6 ± 8 mm Hg; cuff 14 ± 19 mm Hg; p < 0.0001; loss/initially occluded: CAT 17 of 61, SWAT-T 5 of 61, cuff 40 of 64, p < 0.01). CAT pressures before turn did not have a clear relationship with turns to occlusion. CONCLUSIONS: Limb circumference/tourniquet width occlusion pressure predictions are not good substitutes for measurements. The wider SWAT-T has lower occlusion and completion pressures than the CAT. Decreases in muscle tension lead to decreases in tourniquet pressure, especially with the nonelastic CAT, which can lead to occlusion loss.