Plasma metabolomics identifies key metabolites and improves prediction of diabetic retinopathy: development and validation across multi-national cohorts.

PURPOSE: To identify longitudinal metabolomic fingerprints of diabetic retinopathy (DR) and evaluate their utility in predicting DR development and progression. DESIGN: Multicenter, multi-ethnic cohort study. PARTICIPANTS: This study included 17,675 participants with baseline pre-diabetes/diabetes, in accordance with the 2021 American Diabetes Association guideline, and free of baseline DR from the UK Biobank (UKB); and an additional 638 diabetic participants from the Guangzhou Diabetic Eye Study (GDES) for external validation. METHODS: Longitudinal DR metabolomic fingerprints were identified through nuclear magnetic resonance assay in UKB participants. The predictive value of these fingerprints for predicting DR development were assessed in a fully withheld test set. External validation and extrapolation analyses of DR progression and microvascular damage were conducted in the GDES cohort. Model assessments included the C-statistic, net classification improvement (NRI), integrated discrimination improvement (IDI), calibration, and clinical utility in both cohorts. MAIN OUTCOME MEASURES: DR development, progression, and retinal microvascular damage. RESULTS: Of 168 metabolites, 118 were identified as candidate metabolomic fingerprints for future DR development. These fingerprints significantly improved the predictability for DR development beyond traditional indicators (C-statistic: 0.802, 95% CI, 0.760-0.843 vs. 0.751, 95% CI, 0.706-0.796; P = 5.56×10-4). Glucose, lactate, and citrate were among the fingerprints validated in the GDES cohort. Using these parsimonious and replicable fingerprints yielded similar improvements for predicting DR development (C-statistic: 0.807, 95% CI, 0.711-0.903 vs. 0.617, 95% CI, 0.494, 0.740; P = 1.68×10-4) and progression (C-statistic: 0.797, 95% CI, 0.712-0.882 vs. 0.665, 95% CI, 0.545-0.784; P = 0.003) in the external cohort. Improvements in NRIs, IDIs, and clinical utility were also evident in both cohorts (all P <0.05). In addition, lactate and citrate were associated to microvascular damage across macular and optic disc regions (all P <0.05). CONCLUSIONS: Metabolomic profiling has proven effective in identifying robust fingerprints for predicting future DR development and progression, providing novel insights into the early and advanced stages of DR pathophysiology.

Three Ru(II) complexes modulate the antioxidant transcription factor Nrf2 to overcome cisplatin resistance.

Here, we designed, synthesized and characterized three new cyclometalated Ru(II) complexes, [Ru(phen)2(1-(4-Ph-Ph)-IQ)]+ (phen = 1,10-phenanthroline, IQ = isoquinoline, RuIQ9), [Ru(phen)2(1-(4-Ph-Ph)-7-OCH3-IQ)]+ (RuIQ10), and [Ru(phen)2(1-(4-Ph-Ph)-6,7-(OCH3)2-IQ)]+ (RuIQ11). The cytotoxicity experiments conducted on both 2D and 3D multicellular tumor spheroids (MCTSs) indicated that complexes RuIQ9-11 exhibited notably higher cytotoxicity against A549 and A549/DDP cells when compared to the ligands and precursor compounds as well as clinical cisplatin. Moreover, the Ru(II) complexes displayed low toxicity when tested on normal HBE cells in vitro and exposed to zebrafish embryos in vivo. In addition, complexes RuIQ9-11 could inhibit A549 and A549/DDP cell migration and proliferation by causing cell cycle arrest, mitochondrial dysfunction, and elevating ROS levels to induce apoptosis in these cells. Mechanistic studies revealed that RuIQ9-11 could suppress the expression of Nrf2 and its downstream antioxidant protein HO-1 by inhibiting Nrf2 gene transcription in drug-resistant A549/DDP cells. Simultaneously, they inhibited the expression of efflux proteins MRP1 and p-gp in drug-resistant cells, ensuring the accumulation of the complexes within the cells. This led to an increase in intracellular ROS levels in drug-resistant cells, ultimately causing damage and cell death, thus overcoming cisplatin resistance. More importantly, RuIQ11 could effectively inhibit the migration and proliferation of drug-resistant cells within zebrafish, addressing the issue of cisplatin resistance. Accordingly, the prepared Ru(II) complexes possess significant potential for development as highly effective and low-toxicity lung cancer therapeutic agents to overcome cisplatin resistance.

Integrated image-based deep learning and language models for primary diabetes care.

Primary diabetes care and diabetic retinopathy (DR) screening persist as major public health challenges due to a shortage of trained primary care physicians (PCPs), particularly in low-resource settings. Here, to bridge the gaps, we developed an integrated image-language system (DeepDR-LLM), combining a large language model (LLM module) and image-based deep learning (DeepDR-Transformer), to provide individualized diabetes management recommendations to PCPs. In a retrospective evaluation, the LLM module demonstrated comparable performance to PCPs and endocrinology residents when tested in English and outperformed PCPs and had comparable performance to endocrinology residents in Chinese. For identifying referable DR, the average PCP's accuracy was 81.0% unassisted and 92.3% assisted by DeepDR-Transformer. Furthermore, we performed a single-center real-world prospective study, deploying DeepDR-LLM. We compared diabetes management adherence of patients under the unassisted PCP arm (n = 397) with those under the PCP+DeepDR-LLM arm (n = 372). Patients with newly diagnosed diabetes in the PCP+DeepDR-LLM arm showed better self-management behaviors throughout follow-up (P < 0.05). For patients with referral DR, those in the PCP+DeepDR-LLM arm were more likely to adhere to DR referrals (P < 0.01). Additionally, DeepDR-LLM deployment improved the quality and empathy level of management recommendations. Given its multifaceted performance, DeepDR-LLM holds promise as a digital solution for enhancing primary diabetes care and DR screening.

Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community-based prospective study.

AIM: The paradoxical protective association between overweight/obesity and diabetic microvascular complications (DMC), a phenomenon well-known as the obesity paradox, has been considered a non-causal association based on methodological influences. We aimed to investigate the association of generalized and abdominal obesity, as measured by body mass index (BMI) and waist circumference (WC), respectively, with DMC in patients with type 2 diabetes (T2D), using a causal inference approach. MATERIALS AND METHODS: We enrolled 1436 patients with clinically diagnosed T2D but not DMC at baseline in a community-based prospective cohort in China between 2017 and 2019 and followed them annually until 2022 with new-onset DMC recorded. Marginal structural Cox models with inverse probability weighting were constructed to determine the causal association. Subgroup analyses were performed to identify potential effect modifiers. RESULTS: We observed 360 incident DMC cases, including 109 cases of diabetic nephropathy (DN) and 277 cases of diabetic retinopathy (DR) during four follow-up visits. Multivariable-adjusted hazard ratios (95% confidence intervals) for overall DMC, DN and DR were 1.037 (1.005-1.071), 1.117 (1.062-1.175) and 1.018 (0.980-1.059) for 1 kg/m2 increase in BMI, and 1.005 (0.994-1.017), 1.034 (1.018-1.051) and 1.000 (0.987-1.014) for 1 cm increase in WC, respectively. Similar patterns were observed across the BMI and WC categories, while the positive association appeared to be more pronounced in women. CONCLUSIONS: Generalized but not abdominal obesity was associated with an increased risk for the overall DMC, whereas both obesities were causally related to DN, albeit not DR, in T2D. Routine weight management should not be neglected in diabetes care, particularly in women.

Abnormal expression of LCA and CD43 in SCLC: a rare case report and brief literature review.

BACKGROUND: To present an unusual case of abnormal LCA expression and CD43 in SCLC and to review the reported literature to avoid potential diagnostic pitfalls. CASE PRESENTATION: A 73-year-old male patient suffered from persistent back pain for more than one month. MRI revealed a compression fracture of the L1-L5 vertebra. A CT scan revealed multiple nodules and masses at the left root of the neck, lung hilum and mediastinum, and multiple areas of bony destruction of the ribs. Histology of the tumor revealed that small and round cells were arranged in nests with areas of necrosis. The tumor cells were round to ovoid with scant cytoplasm and indistinct cell borders. The nuclear chromatin was finely granular, and the nucleoli were absent or inconspicuous. Immunohistochemically, the tumor cells were positive for cytokeratin, TTF-1, POU2F3, LCA, and CD43. CONCLUSION: This report highlights a potential diagnostic pitfall in the diagnosis of SCLC, urges pathologists to exercise caution in cases of LCA and CD43 positivity and illustrates the need for further immunohistochemical studies to avoid misdiagnosis.

Myopia and Rate of Peripapillary Retinal Nerve Fiber Layer Thickness in Diabetic Patients Without Retinopathy: A 2-Year Longitudinal Study.

PURPOSE: The aim of this study was to investigate the association between myopia and longitudinal changes in peripapillary retinal nerve fiber layer (pRNFL) thickness in type 2 diabetic patients without diabetic retinopathy (DR). METHODS: A total of 1069 participants with a median follow-up time of 1.9 years were included in this study. The participants were categorized into four groups based on the presence of myopia (≤ -0.5 diopter [D]) and diabetes without DR, including a control group (n = 412), diabetes group (n = 416), myopia group (n = 115), and diabetes + myopia group (n = 126). Peripapillary average and sectoral RNFL measurements were obtained using 6 × 6 mm swept-source optical coherence tomography (SS-OCT) scans centered at the optic disc. The change rate of pRNFL, adjusted for age and sex, was calculated and compared among the four groups to investigate the impact of myopia and diabetes. RESULTS: The baseline estimated pRNFL thickness after adjustment for covariates was 113.7 µm, 116.2 µm, 108.0 µm, and 105.6 µm in the control, diabetes, myopia, and diabetes + myopia group, respectively (diabetes > control > myopia = diabetes + myopia, p < 0.001). The respective average pRNFL loss in the four groups was -0.48 µm/year, -1.11 µm/year, -1.23 µm/year, and -2.62 µm/year (all p < 0.01). The diabetes + myopia group exhibited a greater rate of average pRNFL reduction compared to the other groups (all p < 0.001). Multivariate analysis using a linear mixed-effects model showed that age, diabetes, axial length (AL), and baseline pRNFL thickness were significantly associated with the rate of average pRNFL reduction. CONCLUSIONS: The diabetes group showed a faster rate of average pRNFL thickness reduction compared to healthy controls, regardless of the presence of myopia. The average pRNFL thickness decreased more rapidly when diabetes and myopia were present simultaneously than in the individual diabetes or myopia group. Both diabetes and myopia were associated with accelerated pRNFL loss.

POU2F3-positive small cell carcinoma of the bladder: A clinicopathologic analysis of 4 cases and literature review.

POU class 2 homeobox 3 (POU2F3)-positive small cell bladder carcinoma (SCBC) is an extremely rare entity, and its clinicopathologic features have not been fully described. Here, we investigated the clinicopathologic features of 4 cases of POU2F3-positive small cell bladder carcinoma (SCBC) and reviewed the literature. We collected 12 cases of SCBC from our departmental archives and detected the expression of POU2F3 by immunohistochemical (IHC) staining. Selected cases with or without POU2F3 expression were subjected to gene expression analysis between two different groups using DESeq2 software. We identified 4 POU2F3-positive SCBC patients, 2 males and 2 females, with a mean age of 77 years. Three patients had hematuria, and 1 patient had dysuria. Radiologic findings showed a bladder mass. Pathologic diagnosis showed that 3 cases were pure SCBC and 1 was mixed urothelial cancer (UC). Histopathologically, four POU2F3-positive SCBC tumors were composed of small round cells with sparse cytoplasm, the nuclei were salt-and-pepper-like or finely granular. Tumor cells showed characteristic cytoplasmic staining with punctate positive signals for cytokeratin. Syn and CD56 were diffusely positive in all the 4 patients. CgA was positive in only one patient. POU2F3-positive SCBC showed higher expression levels of POU2F3, HMGA2 and PLCG2 genes by RNA-Seq. Our data showed the specific clinicopathologic features of 4 rare POU2F3-positive SCBC cases, and the distinct molecular feature was observed between POU2F3-positive and negative SCBC in the limited number of cases.

Association of Visceral Obesity Indices With Incident Diabetic Retinopathy in Patients With Diabetes: Prospective Cohort Study.

BACKGROUND: Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. OBJECTIVE: This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. METHODS: This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. RESULTS: The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariable­adjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). CONCLUSIONS: Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.

Melan-A expression in non-melanocytic carcinoma: A potential diagnostic pitfall.

BACKGROUND: Melan-A/MART-1 is a melanocytic differentiation marker recognized as an antigen on melanoma cells. It is a useful diagnostic marker for pathologists in the diagnosis of melanocytic tumors. However, we recently found that Melan-A can be expressed in some non-melanocytic carcinomas that are rarely reported in the literature. METHODS: We analyzed the expression of Melan-A in 87 non-melanocytic carcinoma tissue samples by immunohistochemistry. Marker positivity was defined as ≥10% positive tumor cells. RESULTS: In 87 non-melanocytic carcinoma tissue samples, Melan-A was positive in six (6.89%) cases, of which four (66.7%) were male and two (33.3%) were female, with a mean age of 60 years (range 21-82 years). Five (83.3%) of the Melan-A-positive cases had distant metastases. Compared with Melan-A negative cases, Melan-A positive non-melanocytic carcinomas were significantly associated with poor prognosis (P=0.0023). CONCLUSIONS: Melan-A expression is relatively rare in non-melanocytic carcinoma cases. This report highlights a potential diagnostic pitfall in the diagnosis of melanoma, urges pathologists to exercise caution in cases of Melan-A positivity, and illustrates the need for an immunohistochemical marker panel to avoid misdiagnosis.

Frailty and risk of microvascular disease in adults with prediabetes.

BACKGROUND AND AIMS: To assess the relationship between frailty phenotypes and the risk of MVD among prediabetics in two prospective cohorts. METHODS: The study included 66,068 and 226 participants with prediabetes from the UK Biobank (UKB) and Chinese Ocular Imaging Project (COIP) in Guangzhou, China, respectively. Frailty was evaluated using the Fried phenotype, which includes weight loss, fatigue, low grip strength, low physical activity, and slow walking pace. The outcome was incident microvascular diseases, including diabetic retinopathy, nephropathy, and neuropathy in UKB, and decline rate of retinal capillary density in COIP. Cox models were used to calculate hazard ratios (HRs) and 95 % confidential intervals (CIs), and mixed linear model was used to determine the ß and 95 % CIs. RESULTS: At baseline, 27,491 (41.6 %) and 3332 (5.0 %) prediabetics were classified as pre-frail and frail, respectively in UKB. During a median follow-up of 8.9 years, 3784 cases of incident microvascular diseases were identified. Pre-frailty and frailty were significantly associated with a higher risk of microvascular diseases (HR 1.21 [1.12, 1.30] for pre-frailty; HR 1.60 [1.42, 1.81] for frailty). Compared to no frailty, the adjusted HRs for frailty were 1.42 (0.73, 2.76) for retinopathy, 1.49 (1.31, 1.70) for nephropathy, and 2.37 (1.69, 3.33) for neuropathy. Fatigue and walking pace were the strongest mediators of frailty and microvascular diseases. In the COIP, the lowest handgrip strength group exhibited 62%-63 % faster annually decline in retinal capillary density compared with the highest group (all P<0.05). CONCLUSIONS: Each frailty point is important for prediabetics because both pre-frailty and frailty phenotypes are strongly associated with an increased risk of microvascular diseases and its subtypes. Lower handgrip strength presents with faster decline in retinal capillary density.

Optimizing hepatocellular carcinoma disease staging systems by incorporating tumor micronecrosis: A multi-institutional retrospective study.

Tumor micronecrosis is a pathological feature that reflects malignant biological behavior in hepatocellular carcinoma (HCC). However, whether micronecrosis can optimize HCC staging systems remains unilluminated. A total of 1632 HCC patients who underwent curative hepatectomy in four institutions from January 2014 to December 2021 were enrolled in this study. Independent prognostic factors were identified, and optimized staging models were established using a training cohort (n = 934). The performance of optimized staging models was validated using an external cohort consisting of cases from three other institutions (n = 232). In addition, patients from our prospectively collected database (n = 379) tested the application effectiveness of the models. Harrel's c-statistics and the corrected Akaike information criterion (AICc) were used to assess the performance of staging models. In most of Barcelona Clinic Liver Cancer (BCLC) and tumor (T) stages, HCC patients with tumor micronecrosis showed poorer prognosis than those without. Tumor micronecrosis, microvascular invasion, multiple tumors and tumor size >2 cm were independent prognostic-related factors. The BCLC and T staging models incorporating tumor micronecrosis showed better performance than the original systems (c-statistic, 0.712 and 0.711 vs. 0.664 and 0.679; AICc, 2314.8 and 2322.3 vs. 2338.2 and 2338.1; respectively). Furthermore, the external validation cohort confirmed that the optimized staging models had improved efficiency compared with the original ones. Moreover, the prospective cohort demonstrated the applicability of the optimized staging systems. Tumor micronecrosis plays a stage-ascending role in HCC patients. The BCLC and T staging systems incorporating tumor micronecrosis can improve the prognosis stratification efficiency of patients.

Iris volume change with physiologic mydriasis to identify development of angle closure: the Zhongshan Angle Closure Prevention Trial.

AIMS: To assess dynamic change of iris area (Iarea) and volume (VOL) with physiologic pupil dilation for progression of primary angle closure suspects. METHODS: Participants underwent baseline examinations including gonioscopy and anterior segment OCT (AS-OCT) as part of the Zhongshan Angle Closure Prevention Trial. The AS-OCT images were obtained both in the dark and light. Progression was defined as development of primary angle closure or an acute angle closure attack. Static ocular biometrics and dynamic changes were compared between progressors and non-progressors and multivariable logistic regression was developed to assess risk factors for progression. RESULTS: A mean 16.8% decrease in Iarea and a mean 6.26% decrease in VOL occurred with pupil dilation, while 22.96% non-progressors and 40% progressors presented VOL increases with pupil dilation. Iarea in light and dark and VOL in light were significantly smaller in progressors. In a multivariable logistic model, older age (p=0.008), narrower horizontal angle opening distance (AOD) 250 µm from the scleral spur (AOD250, p=0.001), flatter iris curvature (IC, p=0.006) and lower loss of iris volume (ΔVOL, p=0.04) were significantly associated with progression. With receiver operating characteristic analysis, the area under the curve for ΔVOL alone was 0.621, while that for the combined index (age, AOD250, IC and ΔVOL) was 0.824. Eyes with elevated intraocular pressure had less VOL loss compared with progressors developing peripheral anterior synechiae alone (p=0.055 for ΔVOL adjusted for pupil enlargement). CONCLUSION: A smaller change in ΔVOL is an additive risk factor to identify eyes more likely to develop angle closure disease. TRIAL REGISTRATION NUMBER: ISRCTN45213099.

Associations between retinal microvascular flow, geometry, and progression of diabetic retinopathy in type 2 diabetes: a 2-year longitudinal study.

PURPOSE: To determine the association between retinal blood vessel flow and geometric parameters and the risk of diabetic retinopathy (DR) progression through a 2-year prospective cohort study. METHODS: Patients with type 2 diabetes mellitus (T2DM) were recruited from a diabetic registry between November 2017 and March 2019. All participants underwent standardized examinations at the baseline and 2-year follow-up visit, and the presence and severity of DR were assessed based on standard seven-field color fundus photographs. They also underwent swept-source optical coherence tomography angiography (OCTA) imaging to obtain measurements of foveal avascular zone area, blood vessel density (VD), fractal dimension (FD), blood vessel tortuosity (BVT) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). RESULTS: A total of 233 eyes of 125 patients were included, and 40 eyes (17.17%) experienced DR progression within 2 years. DR progression was significantly associated with lower baseline VD (odds ratio [OR] 2.323 per SD decrease; 95% confidence interval [CI] 1.456-3.708; P < 0.001), lower FD (OR, 2.484 per SD decrease; 95% CI 1.268-4.867; P = 0.008), and higher BVT (OR, 2.076 per SD increase; 95% CI 1.382-3.121; P < 0.001) of the DCP after adjusting for confounding factors. The addition of OCTA metrics improved the predictive ability of the original model for DR progression (area under the curve [AUC] from 0.725 to 0.805; P = 0.022). CONCLUSIONS: OCTA-derived VD, FD and BVT in the DCP were independent predictors of DR progression and showed additive value when added to established risk models predicting DR progression.

Impacts of Chronic Kidney Disease on Retinal Neurodegeneration: A Cross-Cohort Analysis.

PURPOSE: To assess the cross-sectional and longitudinal associations between chronic kidney disease (CKD) and ganglion cell-inner plexiform layer (GCIPL) thickness in a UK Biobank population and a Chinese cohort. DESIGN: Prospective observational cohort study and cross-sectional study. METHOD: This study included 23,014 individuals without neurodegenerative diseases from the UK Biobank, and 3 years of annual follow-up data of 2197 individuals from a Chinese cohort. Three groups were defined by estimated glomerular filtration rate (eGFR) based on serum creatinine classifying CKD severity as no CKD, mild CKD, and moderate to severe CKD (MS-CKD). GCIPL thickness, measured using optical coherence tomography, was analyzed through linear regression over time to determine its decline rate in micrometers per year. Linear regression models were used to assess the correlation between renal function and both the baseline GCIPL thickness and the GCIPL decline rate. RESULTS: The cross-sectional analysis in a largely white population showed that poorer renal function negatively correlated with GCIPL thickness with a mean of 0.15 µm thinner (95% confidence interval [CI] -0.30 to -0.01; P = .042) in mild CKD and 0.83 µm thinner (95% CI -1.34 to -0.32; P = .001) in MS-CKD compared with that of control subjects without CKD. Longitudinal analysis in the Chinese cohort showed that the GCIPL decreased more rapidly in persons with poorer renal function. After correcting for all confounding factors, the rate of GCIPL thinning was 0.30 µm/year (95% CI -0.41 to -0.19; P < .001) more in the mild CKD group and 0.52 µm/year (95% CI -0.79 to -0.26; P < .001) more in the MS-CKD group compared with control subjects without CKD. This relationship also occurred in individuals with diabetes or hypertension. CONCLUSIONS: Poor renal function was associated with a lower baseline GCIPL thickness in the UK population and a faster decline rate in Chinese participants. However, the detailed underlying mechanisms still need further exploration.

The action logic of the older adults about health-seeking in South Rural China.

BACKGROUND: The Chinese government has invested significant resources to build many rural healthcare stations. However, in the face of convenient medical paths and accessible medical resources, the utilization rate of health services for older adults in rural areas is surprisingly low. This study explored why health-seeking behavior among older adults in rural China was not active. METHODS: Data were collected through participatory rural appraisal (PRA) with 108 participants in 12 villages in southern China. Daily schedule and social and resource mapping were employed to outline the range of activities and the routine of the older adults, as well as in-depth interviews to understand the logic of their healthcare choices. Data collected were analyzed by content analysis. RESULTS: Three themes were generated: (1) perceptions of health status (being healthy or sick): the rural older adults used the ability to handle routine chores as a measure of health status; (2) prioritization of solving symptoms over curing diseases: the older adults preferred the informal self-medication to cope with diseases, as long as there were no symptoms and no pain; (3) 'unpredictable' troubles: they tended to favor the 'optimal' solution of keeping their lives in order rather than the best medical treatment options. CONCLUSION: This study showed that the medical practices of the rural elderly were profoundly influenced by their perceptions of health and their life experiences. In the face of diseases, they tended to keep their lives in order, preferring self-treatment practices that address symptoms or selectively following medical advice rather than medical and science-based clinical solutions. In the future, the construction of rural health care should focus on changing the 'inaccessibility' of healthcare resources at the subjective level of the rural elderly and develop culturally adaptable health education.

Six-Year Change in Cataract Surgical Coverage and Postoperative Visual Outcomes in Rural Southern China: The Yangxi Eye Study.

PURPOSE: The purpose of this study was to investigate a 6-year change in cataract surgical coverage (CSC), effective cataract surgical coverage (eCSC), and visual outcomes in an elderly population in rural southern China. DESIGN: This is a prospective population-based study with a 6-year follow-up. METHODS: The study included rural residents aged 50 years and above in southern China with comprehensive eye examinations at baseline and follow-up in 2014 and 2020, respectively. RESULTS: Five thousand six hundred thirty-eight participants underwent baseline examinations (mean age 66.1±10.2 y, 50.8% women); and 3141 (64.9%) of 4841 eligible survivors attended the 6-year follow-up. Cataract surgical coverage was 41.7% and 40.6% at baseline and follow-up, respectively, while eCSC were 32.6% and 26.6%. In multivariate models, the 6-year likelihood of cataract surgery decreased with older age [odds ratio (OR)=0.97 per year, 95% confidence interval (CI): 0.94, 0.99, P =0.012] and worse baseline presenting uncorrected visual acuity (PVA) in the worse-seeing eye (OR=0.35 per unit logarithm of the minimum angle of resolution (logMAR), 95% CI: 0.25, 0.48, P <0.001), and increased with prior cataract surgical history at baseline (OR=3.88, 95% CI: 1.91, 7.09, P <0.001). The likelihood of receiving effective cataract surgery decreased with worse baseline PVA in the worse eye (OR=0.49 per unit logMAR, 95% CI: 0.24, 0.97, P =0.042) and better-seeing eye (OR=0.68 per unit logMAR, 95% CI: 0.48, 0.95, P =0.026). Posterior capsular opacification was the main reason for PVA <6/18, reporting it in logMAR (0.5) in operated eyes (38.4% at baseline; 28.1% at follow-up). CONCLUSIONS: World Health Organization has established a global target of increasing eCSC by 30% before 2030, but no increase was found in rural southern China between 2014 and 2020, let alone reaching the World Health Organization target of 56.3%. Strategies to improve surgery incidence should focus on older persons and those with worse preoperative PVA.

Serum cystatin C for risk stratification of prediabetes and diabetes populations.

BACKGROUND: The association between serum cystatin C level and vascular outcomes has not been fully elucidated in diabetes and is unclear in prediabetes. We aim to evaluate whether cystatin C level predicts future risk for mortality and vascular outcomes in prediabetes and diabetes. METHODS: A total of 85,371 participants with prediabetes and diabetes, and available baseline cystatin C in the UK biobank were included with a 14-year follow-up. Cox hazards models were used to calculate the associations between cystatin C level, mortality (all-cause, cause-specfic mortality) and vascular outcomes (myocardial infarction [MI], stroke, end-stage renal disease [ESRD] and diabetic retinopathy [DR]). The 1136 diabetes subjects in Guangzhou Diabetic Eye Study (GDES) were included for examing the impact of cystatin C on in vivo retinal degeneration and microvascular changes by using SS-OCT and OCTA. RESULTS: The highest cystatin C quartile had increased risks of all-cause (hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.86-2.19), cardiovascular (HR, 2.29; 95% CI 1.97-2.67), cancer (HR, 1.86; 95% CI 1.65-2.10) and other-cause mortality (HR, 2.24; 95% CI 1.90-2.64), MI (HR, 1.40; 95% CI 1.26-1.55), stroke (HR, 1.88; 95% CI, 1.57-2.26), ESRD (HR, 7.33; 95% CI, 5.02-10.71), DR (HR, 1.17; 95% CI 1.03-1.32) than those in the lowest quartile. Adding cystatin C to the conventional model improved C-statistic for all-cause (0.699-0.724), cardiovascular (0.762-0.789), cancer (0.661-0.674) and other-cause mortality (0.675-0.715), MI (0.748-0.750), stroke (0.712-0.718), and ESRD (0.808-0.827). The GDES analysis identified a strong association between increased cystatin C levels and diminished retinal neural layers, as well as microvascular rarefaction in both macular and optic disc regions (all P < 0.05). CONCLUSIONS: Serum cystatin C refines the risk stratification for mortality and vascular outcomes among patients with prediabetes or diabetes.

Evaluation of a self-imaging OCT for remote diagnosis and monitoring of retinal diseases.

OBJECTIVES: To evaluate the feasibility and accuracy of a portable, self-imaging optical coherence tomography (OCT) for measuring central subfield thickness (CST) and achieving diagnostic concordance for retinal lesions compared with clinic-based spectral-domain OCT (SD-OCT). METHODS: This comparative, cross-sectional study was conducted between August 2020 and February 2021. Two groups of adult participants were recruited: (1) a selected cohort of 160 participants with confirmed diagnosis and (2) a consecutive cohort of 315 participants recruited randomly. All participants underwent self-imaging OCT examination, as well as standard OCT examination. CST was automatically calculated for comparisons between the two OCT devices. Diagnostic concordance for retinal lesions and the success rate of self-imaging were assessed within the consecutive cohort. RESULTS: In the selected cohort, self-imaging OCT images yielded consistent CST with SD-OCT, with a mean difference of 0.1±7.7 µm for normal eyes, 4.9±10.6 µm for macular oedema, -1.3±9.5 µm for choroidal neovascularisation, 5.0±7.8 µm for epiretinal membrane. The self-imaging OCT also demonstrated good repeatability, with a mean test-retest difference in CST of 0.7±3.9 µm and limits of agreement ranging from -6.9 to 8.3 µm. Additionally, within the consecutive cohort, interdevice κ values ranged for detecting various retinal lesions ranged from 0.8 to 1.0, except in the cases of retinal detachment (κ=0.5). All eyes (100%) in the selected cohort and 242 eyes (76.8%) in the consecutive cohort successfully completed self-imaging. Participants spent less time on self-imaging compared with SD-OCT operated by a technician (66.7±20.1 vs 73.3±32.5, p<0.01). A majority of participants (90%) found the self-imaging process 'easy' and 'comfortable'. CONCLUSIONS AND RELEVANCE: This study demonstrates that our self-imaging OCT and clinical-used SD-OCT are highly consistent not only in measuring the CST but also in identifying most retinal lesions.

Deep Learning Performance of Ultra-Widefield Fundus Imaging for Screening Retinal Lesions in Rural Locales.

Importance: Retinal diseases are the leading cause of irreversible blindness worldwide, and timely detection contributes to prevention of permanent vision loss, especially for patients in rural areas with limited medical resources. Deep learning systems (DLSs) based on fundus images with a 45° field of view have been extensively applied in population screening, while the feasibility of using ultra-widefield (UWF) fundus image-based DLSs to detect retinal lesions in patients in rural areas warrants exploration. Objective: To explore the performance of a DLS for multiple retinal lesion screening using UWF fundus images from patients in rural areas. Design, Setting, and Participants: In this diagnostic study, a previously developed DLS based on UWF fundus images was used to screen for 5 retinal lesions (retinal exudates or drusen, glaucomatous optic neuropathy, retinal hemorrhage, lattice degeneration or retinal breaks, and retinal detachment) in 24 villages of Yangxi County, China, between November 17, 2020, and March 30, 2021. Interventions: The captured images were analyzed by the DLS and ophthalmologists. Main Outcomes and Measures: The performance of the DLS in rural screening was compared with that of the internal validation in the previous model development stage. The image quality, lesion proportion, and complexity of lesion composition were compared between the model development stage and the rural screening stage. Results: A total of 6222 eyes in 3149 participants (1685 women [53.5%]; mean [SD] age, 70.9 [9.1] years) were screened. The DLS achieved a mean (SD) area under the receiver operating characteristic curve (AUC) of 0.918 (0.021) (95% CI, 0.892-0.944) for detecting 5 retinal lesions in the entire data set when applied for patients in rural areas, which was lower than that reported at the model development stage (AUC, 0.998 [0.002] [95% CI, 0.995-1.000]; P < .001). Compared with the fundus images in the model development stage, the fundus images in this rural screening study had an increased frequency of poor quality (13.8% [860 of 6222] vs 0%), increased variation in lesion proportions (0.1% [6 of 6222]-36.5% [2271 of 6222] vs 14.0% [2793 of 19 891]-21.3% [3433 of 16 138]), and an increased complexity of lesion composition. Conclusions and Relevance: This diagnostic study suggests that the DLS exhibited excellent performance using UWF fundus images as a screening tool for 5 retinal lesions in patients in a rural setting. However, poor image quality, diverse lesion proportions, and a complex set of lesions may have reduced the performance of the DLS; these factors in targeted screening scenarios should be taken into consideration in the model development stage to ensure good performance.

Cardiovascular and microvascular outcomes according to vitamin D level and genetic variants among individuals with prediabetes: a prospective study.

BACKGROUND: Whether serum vitamin D mediate vascular diseases in prediabetic populations remains unclear. This study aimed to determine the associations between circulating 25-hydroxyvitamin D [25(OH)D] levels and vitamin D receptor (VDR) polymorphisms with the risk of macrovascular complications, including myocardial infarction and stroke, and microvascular complications such as diabetic nephropathy and retinopathy, among adults with prediabetes. METHODS: Participants with prediabetes in UK Biobank were included (N = 56,387). Multivariable dose-response and Cox proportion models were used to explore the relationship of serum 25(OH)D status and the risks of vascular complications. The interaction of VDR polymorphisms with serum 25(OH)D level on risks of vascular events was also assessed. RESULTS: During a median follow-up of 12 years, higher levels of 25(OH)D were significantly and nonlinearly associated with a lower risk of macrovascular diseases among prediabetic individuals. The adjusted hazard ratios (95% confidential interval) of serum 25(OH)D levels of ≥ 75.0 nmol/L versus < 25 nmol/L were 0.75 (0.63-0.88) for myocardial infarction, 0.74 (0.55-1.00) for stroke, 1.02 (0.60-1.74) for diabetic nephropathy, and 1.30 (0.92-1.84) for diabetic retinopathy, respectively. The rs2228570 (FokI) polymorphisms significantly interacted with 25(OH)D on incident myocardial infarction (P-interaction = 0.042) and stroke (P-interaction = 0.033). The individuals with serum 25(OH)D level of 50.0-74.9 nmol/L and rs2228570 (FokI) homozygotes had the lowest risks of vascular complications. CONCLUSIONS: Lower serum 25(OH)D levels are significantly and nonlinearly associated with an increased risk of cardiocerebrovascular diseases in prediabetic individuals, with VDR polymorphisms of rs2228570 (FokI) modify such associations. Monitoring a safe 25(OH)D concentration is suggested to prevent the vascular complications for prediabetes.