Glaucoma is a leading cause of blindness worldwide. Purpose of this study was to identify molecular markers that were significantly correlated with presence of glaucoma and outcome of glaucoma surgery. To accomplish this, we determined the profiles of pro-inflammatory cytokines in the aqueous humor of 101 glaucoma patients; 31 primary open angle glaucoma (POAG), 38 pseudoexfoliation glaucoma (PEG), and 32 neovascular glaucoma (NVG). We also studied 100 normal subjects as controls. In eyes with POAG or PEG, the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and CCL2 were significantly elevated. In the NVG eyes, many inflammatory cytokines were also highly elevated. IL-8 had the highest odds ratio, and levels of IL-8 and CCL2 were significantly correlated with preoperative IOP or visual field defects in PEG eyes. Principal component analysis showed that IL-8 had the highest association to the IOP-cytokine component, and Cox proportional hazard model indicated that an elevation of IL-8 was a significant risk of filtering surgery failure. Together with modeling of their interactions and prognosis, IL-8 elevation is a significant risk factor both for detecting and managing glaucoma and may serve as a therapeutic target candidate to improve the prognosis of glaucoma surgery.
Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fracture. However, the association between diabetes-related osteoporosis and mortality in T2DM remains unknown. This historical cohort study assessed the endpoint of all-cause mortality in patients with T2DM. According to our hospital record, bone parameters were examined in 797 patients from 1997 to 2009. We excluded 78 because of diseases affecting bone metabolism and could not follow-up 308 patients. Finally, in 411 patients, the associations of bone turnover markers, bone mineral density (BMD), and the prevalence of vertebral fractures with mortality were investigated by Cox regression analyses adjusted for confounding factors. Of 411 patients, 56 died during the follow-up period of almost 7 years. Cox regression analyses showed that reduced BMD at the lumbar spine (LS) and femoral neck (FN) (T-score ≤ -2.5) and severe vertebral fractures were associated with higher mortality (hazard ratio [HR] 3.25, 95% confidence interval [CI] 1.48-7.16, p = 0.003 for LS-T score ≤ -2.5; HR 5.19, 95% CI 1.83-14.75, p = 0.002 for FN-T score ≤ -2.5; HR 2.93, 95% CI 1.42-6.02, p = 0.004 for multiple vertebral fractures; HR 7.64, 95% CI 2.13-27.42, p = 0.002 for grade 3 vertebral fracture). Separate analysis in men and women showed that decreased serum osteocalcin was associated with mortality in women (HR 3.82, 95% CI 1.01-14.46 per SD decrease, p = 0.048). The present study is the first to show the association of reduced BMD and severe vertebral fractures with increased all-cause mortality in patients with T2DM. Moreover, higher serum osteocalcin was significantly associated with decreased mortality in women with T2DM.
Corneal opacities are important causes of blindness, and their major etiology is infectious keratitis. Slit-lamp examinations are commonly used to determine the causative pathogen; however, their diagnostic accuracy is low even for experienced ophthalmologists. To characterize the “face” of an infected cornea, we have adapted a deep learning architecture used for facial recognition and applied it to determine a probability score for a specific pathogen causing keratitis. To record the diverse features and mitigate the uncertainty, batches of probability scores of 4 serial images taken from many angles or fluorescence staining were learned for score and decision level fusion using a gradient boosting decision tree. A total of 4306 slit-lamp images including 312 images obtained by internet publications on keratitis by bacteria, fungi, acanthamoeba, and herpes simplex virus (HSV) were studied. The created algorithm had a high overall accuracy of diagnosis, e.g., the accuracy/area under the curve for acanthamoeba was 97.9%/0.995, bacteria was 90.7%/0.963, fungi was 95.0%/0.975, and HSV was 92.3%/0.946, by group K-fold validation, and it was robust to even the low resolution web images. We suggest that our hybrid deep learning-based algorithm be used as a simple and accurate method for computer-assisted diagnosis of infectious keratitis.
Background: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of muscle mass reduction. However, the association between muscle mass and mortality in T2DM remains unknown. Methods: This was a historical cohort study with the endpoint of all-cause mortality. This study included 163 Japanese men and 141 postmenopausal women with T2DM whose body compositions were evaluated using dual-energy X-ray absorptiometry. Low muscle mass was defined as a skeletal muscle mass index (SMI) of <7.0 kg/m 2 for men and <5.4 kg/m 2 for women. Results: During the 6-year follow-up period, 32 men and 14 women died. In a Cox regression analysis adjusted for age, T2DM duration, glycated hemoglobin, serum creatinine, fasting C-peptide, body mass index, and lean body mass were associated with the risk of mortality in men [hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 1.00–3.28 per standard deviation (SD) decrease, p = 0.049] and women (HR = 4.53, 95% CI = 1.14–17.96 per SD decrease, p = 0.032). Neither fat mass nor bone mineral content was associated with mortality. Low SMI was associated with increased mortality in women (HR = 5.97, 95% CI = 1.04–34.37, p = 0.045), while the association between low SMI and mortality was marginal in men (HR = 2.38, 95% CI = 0.92–6.14, p = 0.074). Conclusions: Low muscle mass was independently associated with all-cause mortality in patients with T2DM. The preservation of skeletal muscle mass is important to protect patients with T2DM from increased mortality risk.
Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.
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