Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study.

BACKGROUND: Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. METHODS: We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine. RESULTS: One thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4-10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76-0.81(95% CI, 0.73-0.83) for cognitive regress with 4 variables and 0.79-0.83 (95% CI, 0.76-0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75-0.78 (95% CI, 0.72-0.82) for cognitive delay with 10 variables and 0.73-0.82 (95% CI, 0.72-0.85) for motor delay with 4 variables. CONCLUSIONS: Our EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Endonasal endoscopic nasolacrimal duct dissection for primary nasolacrimal duct obstruction.

PURPOSE: The purpose of this study is to describe the results of endonasal endoscopic nasolacrimal duct dissection (EE-NLDD); a surgical technique used for the treatment of primary nasolacrimal duct obstruction (NLDO). MATERIALS AND METHODS: Before the operation, the patency of the nasolacrimal duct (NLD) was evaluated through irrigation and probing. The EE-NLDD surgical procedure involved the removal of the bony structure covering the NLD. The NLD mucosa was dissected and marsupialized with nasal mucosa, creating a mucosa-covered ostium. The bone surrounding the lacrimal fossa and lacrimal sac mucosa was preserved throughout procedure. The postoperative anatomical and functional outcomes were evaluated through irrigation, endonasal endoscopic fluorescein dye test, and subjective descriptions of the patients. STUDY DESIGN: This is a retrospective chart review study which included all patients with primary NLDO treated with EE-NLDD surgical technique from February 2012 to July 2016 in Taipei Medical University Shuang Ho Hospital by a single surgeon (YD, Shen). RESULTS: The mean follow-up time for the 39 patients (43 eyes) was 14.7 months (range: 0.5-46 months). Anatomical patency was achieved in all patients. Under endonasal endoscopy, fluorescein dye was observed at the internal orifice after the dye was instilled into the conjunctival sac in all patients. The complete resolution of the epiphora was reported in 36 patients (39 eyes) and two patients (2 eyes) exhibited an improvement of the epiphora after surgery. However, one patient (2 eyes) reported persistent bilateral epiphora without improvement even under solid evidence of anatomical patency. No major complications were noted intraoperatively or postoperatively. CONCLUSIONS: The results suggested that the EE-NLDD is a safe and effective procedure and has a success rate comparable with that of conventional endonasal dacryocystorhinostomy.

Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.

PURPOSE: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. DESIGN: Cross-sectional study. PARTICIPANTS: We included 42 044 participants in the UK Biobank. The mean age was 56 years. METHODS: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. MAIN OUTCOME MEASURES: Thicknesses of mRNFL, GCC, and GCIPL. RESULTS: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 µm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10-8), greater social deprivation (most significant for GCIPL: -0.28 µm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10-5), lower educational attainment (most significant for mRNFL: -0.36 µm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10-14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 µm [95% CI, -1.86 to -1.43]; P = 2.4×10-50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 µm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10-10) and was not associated significantly with mRNFL (0.00 µm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). CONCLUSIONS: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Low mitochondrial DNA copy number of resected cecum appendix correlates with high severity of acute appendicitis.

BACKGROUND/PURPOSE: The roles of mitochondrial DNA alterations in acute appendicitis (AA) remain unclear. We evaluated the alterations of mtDNA copy number and mtDNA integrity [proportion of mtDNA templates without 8-hydroxyl-2'-deoxyguanosine (8-OHdG)] of the resected cecum appendixes in clinically suspected acute appendicitis (CSAA). METHODS: A total of 228 CSAA patients, including 50 harbored negative AA (NAA), 155 true AA (TAA) without rupture and 23 TAA with rupture, who underwent appendectomies were enrolled. Tissues of resected cecum appendixes from the paraffin-embedded pathological blocks were subjected to DNA extraction, and their mtDNA copy number and mtDNA integrity were determined by quantitative real-time polymerase chain reaction (Q-PCR). RESULTS: During the progression of disease severity from NAA to TAA without rupture and further TAA with rupture, increases of white blood cell (WBC) counts (p = 0.001), positive bacterial culture rates in turbid ascites (p = 0.016) and area (p < 0.001)/or volume (p < 0.001) indices of resected cecum appendixes were noted among CSAA patients. On the contrary, decrease of mtDNA copy number (p = 0.003) was observed during disease progression of CSAA patients, especially in female patients (p = 0.007). Furthermore, lower mtDNA copy numbers were correlated with higher WBC counts (p = 0.001) and larger area (p = 0.003) or volume (p < 0.001) indices of the resected cecum appendixes. However, such an alteration was not observed in mtDNA integrity of resected cecum appendixes. CONCLUSION: We conclude that a low mtDNA copy number of the resected cecum appendix may reflect high severity of acute appendicitis.

Association of Retinal Nerve Fiber Layer Thinning With Current and Future Cognitive Decline: A Study Using Optical Coherence Tomography.

Importance: Identifing potential screening tests for future cognitive decline is a priority for developing treatments for and the prevention of dementia. Objective: To examine the potential of retinal nerve fiber layer (RNFL) thickness measurement in identifying those at greater risk of cognitive decline in a large community cohort of healthy people. Design, Setting, and Participants: UK Biobank is a prospective, multicenter, community-based study of UK residents aged 40 to 69 years at enrollment who underwent baseline retinal optical coherence tomography imaging, a physical examination, and a questionnaire. The pilot study phase was conducted from March 2006 to June 2006, and the main cohort underwent examination for baseline measures from April 2007 to October 2010. Four basic cognitive tests were performed at baseline, which were then repeated in a subset of participants approximately 3 years later. We analyzed eyes with high-quality optical coherence tomography images, excluding those with eye disease or vision loss, a history of ocular or neurological disease, or diabetes. We explored associations between RNFL thickness and cognitive function using multivariable logistic regression modeling to control for demographic as well as physiologic and ocular variation. Main Outcomes and Measures: Odds ratios (ORs) for cognitive performance in the lowest fifth percentile in at least 2 of 4 cognitive tests at baseline, or worsening results on at least 1 cognitive test at follow-up. These analyses were adjusted for age, sex, race/ethnicity, height, refraction, intraocular pressure, education, and socioeconomic status. Results: A total of 32 038 people were included at baseline testing, for whom the mean age was 56.0 years and of whom 17 172 (53.6%) were women. A thinner RNFL was associated with worse cognitive performance on baseline assessment. A multivariable regression controlling for potential confounders showed that those in the thinnest quintile of RNFL were 11% more likely to fail at least 1 cognitive test (95% CI, 2.0%-2.1%; P = .01). Follow-up cognitive tests were performed for 1251 participants (3.9%). Participants with an RNFL thickness in the 2 thinnest quintiles were almost twice as likely to have at least 1 test score be worse at follow-up cognitive testing (quintile 1: OR, 1.92; 95% CI, 1.29-2.85; P < .001; quintile 2: OR, 2.08; 95% CI, 1.40-3.08; P < .001). Conclusions and Relevance: A thinner RNFL is associated with worse cognitive function in individuals without a neurodegenerative disease as well as greater likelihood of future cognitive decline. This preclinical observation has implications for future research, prevention, and treatment of dementia.

Influence of visual impairment and hearing impairment on functional dependence status among people in Taiwan-An evaluation using the WHODAS 2.0 score.

BACKGROUND: Visual impairment (VI) and hearing impairment (HI) are the two most common types of sensory disability encountered clinically. However, VI and HI result in different limitations in daily life. We assessed the level of functioning in patients with VI or HI based on the International Classification of Functioning, Disability, and Health. METHODS: This nationwide, cross-sectional study included 312 people with VI and 540 people with HI. Each participant's degree of functioning and disability was evaluated using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The standardized WHODAS 2.0 scores ranged from 0 (least difficulty) to 100 (most difficulty). RESULTS: Patients with VI and those with HI had a mean (±standard error) 32-item WHODAS 2.0 score of 42.4 ± 2.9 and 27.1 ± 1.6, respectively. The degree of restriction was positively related to the level of VI. Specifically, the patients with VI and a WHODAS 2.0 score of 33.7-35.3 or higher were likely to experience barriers to accessing mobility products, communication products, and education products. Furthermore, patients with a score of 42.9 or higher might experience barriers to accessing ingestion products and living products. CONCLUSION: WHODAS 2.0 scores are strongly correlated with the severity of VI. Mild VI should be targeted for treatment and referral as early as possible. Compared with the patients with HI, the patients with VI more frequently experience barriers to accessing environmental factors.

Associations with Retinal Pigment Epithelium Thickness Measures in a Large Cohort: Results from the UK Biobank.

PURPOSE: To describe associations of ocular and systemic factors with retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite community-based study. This research has been conducted using the UK Biobank Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to 69 years old received questionnaires, physical examination, and eye examination, including macular SD OCT. Systematic selection process identified 34 652 eyes with high-quality SD OCT images from normal individuals for analysis. METHODS: We included people with no self-reported ocular disease, diabetes, or neurologic disorders; visual acuity of ≥20/25; refraction between -6 diopters (D) to 6 D, and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with central, stable fixation were included. Descriptive statistics, t tests, and regression analyses were performed. Multivariate regression modeling was used to adjust for covariates and to identify relationships between RPE-BM thickness and ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium-BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields. RESULTS: Mean RPE-BM thickness was 26.3 µm (standard deviation, 4.8 µm) at central subfield. Multivariate regression with age stratification showed that RPE thinning became apparent after age 45. Among those aged ≤45, RPE-BM was significantly thicker among those of black or mixed/other race (+3.61 and +1.77 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.4 µm/D; P < 0.001), but not for other variables considered. Among those age >45, RPE-BM was significantly thinner with older age (-0.10 µm/year; P < 0.001), Asian ethnicity (-0.45 µm vs. white; P = 0.02), taller height (-0.02 µm/cm; P < 0.001), higher IOP (-0.03 µm/mmHg; P < 0.001), and regular smoking (-0.27 µm vs. nonsmokers; P = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other race (+3.29 µm and +0.81 µm vs. white, respectively; P < 0.001) and higher hyperopia (+0.28 µm/D; P < 0.001). There was no significant association with sex or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness in normal individuals, a structure that varies with age, ethnicity, refraction, IOP, and smoking. The significant association with IOP is especially interesting and may have relevance for the etiology of glaucoma, while the association between age and smoking may have relevance for the etiology of age-related macular degeneration.

Prevalence of Glaucoma in the United States: The 2005-2008 National Health and Nutrition Examination Survey.

PURPOSE: To estimate the prevalence of glaucoma in the US population based on optic nerve head photography, to estimate the prevalence of glaucoma awareness, and to identify demographic and ocular risk factors for being unaware of having glaucoma. METHODS: The study included 5746 men and women 40 years of age and older participating in the National Health and Nutrition Examination Survey (NHANES) 2005-2008. Each participant had 45° photographs of the macula and optic disc of both eyes. Fundus photographs were first graded by a reading center, and those with a cup-to-disc ratio (CDR) ≥ 0.6 were regraded by three glaucoma specialists to determine the presence or absence of glaucoma. Analyses were performed using NHANES weights to account for the complex multistage probability sampling design. RESULTS: The estimated overall prevalence of glaucoma in the US civilian, noninstitutionalized population 40 years of age and older was 2.1% (95% confidence interval [CI], 1.7%-2.6%). Glaucoma affected 2.9 million individuals, including 1.4 million women; 1.5 million men; 2.3 million people 60 years of age and older; and 0.9 million blacks, Mexican Americans, and people of other races. The prevalence of glaucoma was highest in non-Hispanic blacks, followed by non-Hispanic whites, Mexican Americans, and others. Over half of participants with glaucoma were unaware that they had the disease. CONCLUSIONS: The prevalence of glaucoma based on optic nerve fundus photography assessment in the general US population 40 years of age and older was 2.1%. Approximately half of glaucoma cases were previously undiagnosed. Studies to determine whether and how to identify undiagnosed glaucoma are an important next step.

Diabetes, Triglyceride Levels, and Other Risk Factors for Glaucoma in the National Health and Nutrition Examination Survey 2005-2008.

PURPOSE: To determine risk factors for glaucoma in a population-based study in the United States. METHODS: Participants age 40 and older from the National Health and Nutrition Examination Survey underwent questionnaires, physical examination, laboratory tests, and vision tests including fundus imaging. Glaucoma was determined based on expert grading of fundus photographs. Regression modeling of glaucoma risk factors was performed. RESULTS: Participants with glaucoma (172) were older (mean age 68.1 [95% confidence interval (CI) 65.6-70.7] vs. 56.4 years [95% CI 55.6-57.2, P < 0.001]), likely to have less than high school education (25.1% vs. 18.1%, P = 0.05), to have diabetes (23.1% vs. 10.8%, P < 0.001), to have central obesity (72.5% vs. 60.7%, P = 0.01), to have systolic hypertension (30.3% vs. 20.1%, P = 0.01), to have diastolic hypotension (30.3% vs. 13.9%, P < 0.001), and to be nonsmokers (91.0% vs. 79.3%, P = 0.002). Sex, poverty, access to health care, fasting glucose, insulin dependence, body mass index, cholesterol levels, diastolic hypertension, systolic hypotension, obstructive sleep apnea, and marijuana were not associated with glaucoma. Multivariable modeling showed associations between glaucoma and older age (odds ratio [OR] 1.09 per year, 95% CI 1.04-1.14), black race (OR 4.40, 95% CI 1.71-11.30), and poverty (OR 3.39, 95% CI 1.73-6.66). Diabetes was no longer associated with glaucoma after adjustment for triglyceride levels. Sex, education, insurance status, body mass index, blood pressure, obstructive sleep apnea, and smoking were not associated with glaucoma. CONCLUSIONS: People who are older, of black race, and with lower income levels have a higher prevalence of glaucoma. A novel association between diabetes, triglyceride levels, and glaucoma is also identified.

Spectral-Domain Optical Coherence Tomography Imaging in 67 321 Adults: Associations with Macular Thickness in the UK Biobank Study.

PURPOSE: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. DESIGN: Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. PARTICIPANTS: Adults from the United Kingdom aged 40 to 69 years. METHODS: Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II; Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS]; Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (<0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty. MAIN OUTCOME MEASURES: Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. RESULTS: The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) µm, with 95% confidence limits of 220.8 and 311.5 µm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P < 0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia. CONCLUSIONS: We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.

Evaluation of Frequency-Doubling Technology Perimetry as a Means of Screening for Glaucoma and Other Eye Diseases Using the National Health and Nutrition Examination Survey.

IMPORTANCE: Glaucoma is a significant cause of global blindness and there are, as yet, no effective means of screening. OBJECTIVE: To assess the potential role of frequency-doubling technology (FDT) perimetry in screening for glaucoma using data collected as part of the National Health and Nutrition Examination Survey (NHANES). DESIGN, SETTING, AND PARTICIPANTS: Reanalysis of cross-sectional data of 6797 participants in the 2005-2008 cycles of the NHANES, which evaluated a sample of the noninstitutionalized US population with at least light-perception vision. A subset of optic nerve photographs were regraded by 3 glaucoma specialists in December 2012. Each participant underwent visual field testing, including FDT perimetry screening, and had fundus photographs taken. MAIN OUTCOMES AND MEASURES: Sensitivity and specificity of FDT perimetry to detect glaucoma, macular disease, or decreased visual acuity. RESULTS: A total of 5746 NHANES participants had optic images originally graded. We regraded 1201 images of 1073 eyes of 548 participants with initial cup-disc ratio (CDR) of 0.6 or greater and 423 images of 360 eyes of 180 randomly selected participants with initial CDR less than 0.6. Diagnoses of glaucoma by disc photograph were 1.6% (3 of 180) in the CDR less than 0.6 group and 31.4% (172 of 548) in the CDR of 0.6 or greater group. The sensitivity of FDT was 33% (95% CI, 0%-87%) and specificity was 77% (95% CI, 71%-84%). For the group with at least 1 CDR of 0.6 or greater, sensitivity of FDT was 66% (95% CI, 59%-73%) and specificity was 70% (95% CI, 66%-75%). When analyzed to give FDT credit for identifying glaucoma, macular disease, or decreased visual acuity, the sensitivity of the test was 80% (95% CI, 77%-83%) and the specificity was 83% (95% CI, 82%-84%). Approximately 25% of the NHANES population was not able to successfully complete FDT testing, representing screening failures and decreasing specificity. CONCLUSIONS AND RELEVANCE: Using the 2005-2008 waves of the NHANES as a model of population-based screening for eye disease, FDT perimetry lacks both sensitivity and specificity as a means of screening for glaucoma, the presence of retinal disease, or decreased acuity in a population-based setting. Given that no single test of glaucoma has yet been shown to be appropriate in a screening setting, to our knowledge, investigators should consider novel methods of detecting glaucoma or combinations of tests that might work better in a screening setting.

Primary congenital glaucoma.

Primary congenital glaucoma (PCG) is the most common nonsyndromic glaucoma in infancy, which can lead to blindness, or a lifetime of vision when diagnosed and treated properly. PCG is more common in populations with a higher prevalence of consanguinity and is associated with CYP1B1 gene mutations which show variable expressivity and phenotypes. The immature angle appearance of PCG likely results from arrested development of tissues of neural crest origin in the third trimester, with the severity of abnormality varying according to the stage at which arrested development occurred. Classic symptoms at presentation include tearing, photophobia, blepharospasm, eye rubbing, and irritability. Examination may reveal elevated intraocular pressure, corneal edema, increased corneal diameter, Haab striae, or enlarged axial length. Angle surgery remains the first line treatment for PCG with a recent advance being circumferential trabeculotomy with the potential to incise the whole angle during one operation as oppose to an incremental approach and the associated multiple anesthetics. Once angle surgery fails, either trabeculectomy or glaucoma drainage device surgery may be appropriate.

Association of CD8 T cells with depression and anxiety in patients with liver cirrhosis.

OBJECTIVE: Depression and anxiety frequently co-occur in patients with. cirrhosis, but their underlying biological substrates are unclear. There is now evidence to suggest that depression is accompanied by signs of an immune response. This study investigated the correlation between depression/anxiety and T-lymphocyte subsets in liver cirrhosis patients. METHODS: A total of 59 patients (37 males and 22 females; aged between 26-81 years) with cirrhosis were enrolled in the study. Severity of depression and anxiety were assessed through the Hamilton depressive scale (HAMD, the 24-item version) and the Hamilton anxiety scale (HAMA). T-lymphocyte subsets (CD3, CD4, and CD8) in peripheral blood were determined by flow cytometry. The relationship between lymphocyte subsets and depression/anxiety scores was studied by correlation analysis. RESULTS: The mean total HAMD and HAMA scores for the 59 subjects were 12.8 +/- 10.4 (range = 0-46) and 7.0 +/- 5.7 (range = 0-26), respectively. Fourteen of 59 subjects (23.7%) had HAMD scores equal to or above 20, indicative of depression. The percentage of CD8, but not CD3 or CD4, in T-lymphocyte subsets was positively correlated with depression (HAMD) (r = 0.268, P = 0.043) and anxiety severity (HAMA) (r = 0.321, P = 0.013). After controlling for age and Child-Pugh scores, the correlations were still significant. CONCLUSION: Around one-fourth of cirrhosis patients may have depression, although depression is not related to cirrhosis severity. Our findings are the first to show that depression and anxiety may be associated with increased levels of CD8 in T-lymphocyte subsets in cirrhosis patients, suggesting that an imbalance of T-lymphocyte subsets may be a factor facilitating depression and anxiety in cirrhotic patients. Examination of CD8 T-lymphocytes may prove useful in assessing the potential relationship between depression, anxiety, immunity, and liver cirrhosis.

Physiologic and laboratory correlates of depression, anxiety, and poor sleep in liver cirrhosis.

BACKGROUND: Studies have shown psychological distress in patients with cirrhosis, yet no studies have evaluated the laboratory and physiologic correlates of psychological symptoms in cirrhosis. This study therefore measured both biochemistry data and heart rate variability (HRV) analyses, and aimed to identify the physiologic correlates of depression, anxiety, and poor sleep in cirrhosis. METHODS: A total of 125 patients with cirrhosis and 55 healthy subjects were recruited. Each subject was assessed through routine biochemistry, 5-minutes ECG monitoring, and psychological ratings of depression, anxiety, and sleep. HRV analysis were used to evaluate autonomic functions. The relationship between depression, sleep, and physiologic correlates was assessed using a multiple regression analysis and stepwise method, controlling for age, duration of illness, and severity of cirrhosis. RESULTS: Reduced vagal-related HRV was found in patients with severe liver cirrhosis. Severity of cirrhosis measured by the Child-Pugh score was not correlated with depression or anxiety, and only had a weak correlation with poor sleep. The psychological distress in cirrhosis such as depression, anxiety, and insomnia were correlated specifically to increased levels of aspartate aminotransferase (AST), increased ratios of low frequency to high frequency power, or reduced nonlinear properties of HRV (α1 exponent of detrended fluctuation analysis). CONCLUSIONS: Increased serum AST and abnormal autonomic nervous activities by HRV analysis were associated with psychological distress in cirrhosis. Because AST is an important mediator of inflammatory process, further research is needed to delineate the role of inflammation in the cirrhosis comorbid with depression.

Bevacizumab presurgical treatment for proliferative sickle-cell retinopathy-related retinal detachment.

PURPOSE: To report the use of presurgical intravitreal bevacizumab in the context of proliferative sickle-cell retinopathy with retinal detachment. METHODS: Intravitreal bevacizumab was injected 3 days before the surgical procedure for traction retinal detachment. Vitrectomy, membrane peeling, endolaser, and SF6 gas tamponade were performed. A 37-year-old African American woman presented with hemoglobin sickle-cell disease and temporal retinal detachment with bullous subretinal fluid extending through the fovea associated with an area of active sea-fan retinal neovascularization with preretinal hemorrhage and retinal traction, with 3 associated retinal breaks. RESULTS: The sea-fan neovascularization associated with the traction retinal detachment and the resultant retinal breaks appeared more fibrotic and les vascular than was noted prior to the pre-operative bevacizumab injection. Segmentation and dissection were performed with minimal bleeding, and retinal traction was relieved without difficulty. This was believed to be atypical in the experience of the surgeons. One month postoperatively, vision measured 20/50, and the retina remained attached. CONCLUSION: Further study is necessary to clarify the role of anti-vascular endothelial growth factor in the treatment of proliferative sickle cell retinopathy associated retinal detachment.

Prevalence of nonrefractive visual impairment in US adults and associated risk factors, 1999-2002 and 2005-2008.

CONTEXT: Over the past decade, chronic illnesses with ophthalmic sequelae such as diabetes and diabetic retinopathy have increased. OBJECTIVES: To estimate prevalence of nonrefractive visual impairment and to describe its relationship with demographic and systemic risk factors including diagnosed diabetes. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) examined a representative sample of the US noninstitutionalized population. In 1999-2002 and 2005-2008, 9471 and 10,480 participants aged 20 years or older received questionnaires, laboratory tests, and physical examinations. Visual acuity of less than 20/40 aided by autorefractor was classified as nonrefractive visual impairment. MAIN OUTCOME MEASURE: Nonrefractive visual impairment. RESULTS: Weighted prevalence of nonrefractive visual impairment increased 21% among US adults aged 20 years and older from 1.4% in 1999-2002 to 1.7% in 2005-2008 (P = .03); and increased 40% among non-Hispanic whites aged 20-39 years from 0.5% to 0.7% (P = .008). In multivariable analyses, statistically significant risk factors for nonrefractive visual impairment in 1999-2002 included age (per year odds ratio [OR], 1.07; 95% CI, 1.05-1.09), poverty (OR, 2.18; 95% CI, 1.31-3.64), lack of insurance (OR, 1.85; 95% CI, 1.16-2.95), and diabetes with 10 or more years since diagnosis (OR, 1.93; 95% CI, 1.15-3.25). In 2005-2008, risk factors included age (OR, 1.05; 95% CI, 1.04-1.07), poverty (OR, 2.23; 95% CI, 1.55-3.22), education less than high school (OR, 2.11; 95% CI, 1.54-2.90), and diabetes with 10 or more years since diagnosis (OR, 2.67; 95% CI, 1.64-4.37). Prevalence of diabetes with 10 or more years since diagnosis increased 22% overall from 2.8% to 3.6% (P = .02); and 133% among non-Hispanic whites aged 20-39 years from 0.3% to 0.7% (P < .001). CONCLUSION: Prevalence of nonrefractive visual impairment was significantly higher in 2005-2008 than in 1999-2002 and may be attributable, in part, to higher prevalence of diabetes, an associated risk factor that increased in prevalence during this time period.

Norcantharidin triggers cell death and DNA damage through S-phase arrest and ROS-modulated apoptotic pathways in TSGH 8301 human urinary bladder carcinoma cells.

Norcantharidin (NCTD) is one of the ingredients of blister beetles which have been used in Chinese medicine for a long time. The purpose of this study was to investigate the inhibitory effects of NCTD on TSGH 8301 human bladder cancer cells in vitro and the mechanisms through which it exerts its anticancer action. Cell morphological analysis was performed using a phase-contrast microscope. The percentage of viable cells, cell cycle distribution, sub-G1 phase (apoptosis), reactive oxygen species (ROS) production and the levels of mitochondrial membrane potential (∆Ψ(m)) were analyzed by flow cytometry. DNA condensation and damage were determined by DAPI staining and comet assay. Apoptosis-associated protein level changes in TSGH 8301 cells following exposure to NCTD were examined, measured and determined by western blotting. Analysis of protein translocation was conducted by immunostaining and confocal laser microscopy. The results indicated that NCTD promoted cytotoxic effects, including the induction of cell morphological changes and the decrease in the percentage of viability, the induction of S-phase arrest as well as sub-G1 phase (apoptosis) in TSGH 8301 cells. The activities of caspase-3 and -9 were upregulated following NCTD treatment. Western blotting indicated that NCTD upregulated Fas, FasL, Bax, Bid, cytochrome c, caspase-3, -8 and -9 that led to the induction of apoptosis through the Fas extrinsic pathway. Furthermore, NCTD induced AIF and Endo G that were released from mitochondria to induce apoptosis through the mitochondrial-independent pathway. NCTD upregulated ROS production, downregulated ∆Ψ(m) and ERK, JNK, p38 protein kinases in TSGH 8301 cells. These findings suggest that NCTD triggers apoptosis in TSGH 8301 human bladder cancer cells via the Fas receptor, activation of the caspse-8, -9 and -3, mitochondrial-dependent and -independent pathways. NCTD may be useful for developing new therapeutic regimens for the treatment of bladder cancer.

Willingness to pay for potential enhancements to a low-cost cataract surgical package in rural southern China.

PURPOSE: To assess determinants of patients' willingness to pay (WTP) for potential components of a multi-tiered cataract surgical package offered by a non-governmental organization (NGO) in rural China. DESIGN: Cross-sectional study. METHODS: Demographic and clinical data were collected from 505 patients presenting for cataract screening or surgery in Yangjiang, China. Willingness to pay for potential enhancements to the current surgery package was assessed using a bidding format with random payment cards. RESULTS: Among 426 subjects (84.4%) completing interviews, the mean age was 73.9 ± 7.3 years, 67.6% were women and 73% (n = 310) would pay for at least one offering, with 33-38% WTP for each item. Among those who would pay, the mean WTP for food was US$1.68 ± 0.13, transportation US$3.24 ± 0.25, senior surgeon US$50.0 ± 3.36 and US$89.4 ± 4.19 for an imported intra-ocular lens (IOL). The estimated total recovery from these enhancements under various assumptions would be US$20-50 (compared to the current programme price of US$65). In multivariate models, WTP for the senior surgeon increased with knowledge of a person previously operated for cataract (OR = 2.13, 95% CI 1.42-3.18, p < 0.001). Willingness to pay for the imported IOL increased with knowledge of a previously operated person (OR = 1.85, 95% CI 1.24-2.75, p < 0.01) and decreased with age >75 years (OR = 0.61, 0.40-0.93, p < 0.05). CONCLUSIONS: Opportunities exist to increase cataract programme revenues through multi-tiered offerings in this setting, allowing greater subsidization of low-income patients. Personal familiarity with cataract surgery is important in determining WTP.

Confirmation of and differentiation among primary vascular lesions using ultrasonography.

PURPOSE: To demonstrate the utility of orbital ultrasound in the evaluation and management of suspected orbital vascular lesions. METHODS: Clinical case series of 15 patients with suspected orbital vascular lesions seen in the Neuro-ophthalmology clinic of the Wilmer Eye Institute. The techniques of standardized echography (combined use of a contact B-scan and standardized A-scan) were performed by an experienced echographer, and data obtained were compared with other available imaging modalities to determine appropriate management. Patients were monitored for improvement, stability, or worsening of symptoms and signs. RESULTS: Based on echographic data obtained, 6 patients underwent surgery, 9 were observed over a follow-up period of 0-14 (mean 3.3) years. All patients demonstrated improvement or remained stable, and no complications developed from misdiagnosis during subsequent follow-up. CONCLUSIONS: Orbital ultrasound provides reliable imaging parameters and can be used as the primary imaging modality when evaluating suspected orbital vascular lesions.

Orbital and Cavernous Sinus Lymphoma Masquerading as Post-Herpetic Neuralgia.

We report an unusual case of adult-onset B-cell lymphoma in the cavernous sinus presenting as post-herpetic neuralgia; additionally, we review the literature regarding primary B-cell lymphomas of the cavernous sinus. This case demonstrates the importance of maintaining a suspicion for malignancy when an atypical clinical course is seen, even when presented with seemingly common or innocuous disease.