Targeted therapy in glomerular diseases.

Targeted therapy has emerged as a more precise approach to treat glomerular diseases, focusing on specific molecular or cellular processes that contribute to disease development or progression. This approach complements or replaces traditional immunosuppressive therapy, optimizes supportive care, and provides a more personalized treatment strategy. In this review, we summarize the evolving understanding of pathogenic mechanisms in immune-mediated glomerular diseases and the developing targeted therapies based on these mechanisms. We begin by discussing pan-B-cell depletion, anti-CD20 rituximab, and targeting B-cell survival signaling through the BAFF/APRIL pathway. We also exam specific plasma cell depletion with anti-CD38 antibody. We then shift our focus to complement activation in glomerular diseases, which is involved in antibody-mediated glomerular diseases, such as IgA nephropathy, membranous nephropathy, ANCA-associated vasculitis, and lupus nephritis. Non-antibody-mediated complement activation occurs in glomerular diseases, including C3 glomerulopathy, complement-mediated atypical hemolytic uremic syndrome, and focal segmental glomerulosclerosis. We discuss specific inhibition of terminal, lectin, and alternative pathways in different glomerular diseases. Finally, we summarize current clinical trials targeting the final pathways of various glomerular diseases, including kidney fibrosis. We conclude that targeted therapy based on individualized pathogenesis should be the future of treating glomerular diseases.

Colletotrichum keratitis: A rare yet important fungal infection of human eyes.

BACKGROUND: Colletotrichum is a rare cause of human infection. Previous reports about Colletotrichum keratitis were limited, and most diagnoses from past reports were based on morphological distinction, which could have led to underestimation of the prevalence of Colletotrichum species. OBJECTIVE: We reported phylogenetic analysis, clinical feature and treatment outcome of molecularly diagnosed Colletotrichum keratitis in our hospital. PATIENTS/METHODS: We recruited 65 patients with culture-proven filamentous fungal keratitis between January 1, 2015 and December 30, 2018. Through molecular sequencing including internal transcribed spacer (ITS) and multi-locus phylogenetic analysis of fungal DNA, seven patients were verified as infected with Colletotrichum species, and their medical records were reviewed to determine the clinical characteristics. RESULTS: Six of seven patients had predisposing factors including trauma (5) and immunosuppressive status (1). Six isolates were initially misidentified as other fungi through morphological identification. ITS sequencing identified the isolates belonged to two species complex (SC): C. truncatum and C. gloeosporioides; multi-locus phylogenetic analysis enabled species identification including C. tropicale (3), C. fructicola (2), C. truncatum (1) and C. fusiforme (1). Five patients with C. gloeosporioides SC responded well to medical treatment and two patients with C truncatum SC underwent evisceration because of either no visual potential or intractable pain. CONCLUSIONS: The molecular approach provides accurate diagnosis and raises epidemiological awareness of Colletotrichum keratitis. Through multi-locus phylogenetic analysis, we report the human infections caused by C. tropicale, C. fructicola and C. fusiforme. We also highlight the different clinical outcomes between C. gloeosporioides SC and C. truncatum SC.

Comparison of corneal endothelial cell loss in FLACS: impact on endothelial cells in different regions.

PURPOSE: To compare changes in corneal endothelial parameters after femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification surgery (CPS) in different corneal regions. SETTING: Chang Gung Memorial Hospital, Linkou, Taiwan. DESIGN: Single-center, retrospective. METHODS: Before and 1, 3, and 6 months postoperatively, specular microscopy was performed to measure endothelial cell density (ECD), corneal thickness, hexagonal cell rate (Hex), and coefficient of variation (CoV). Position 1 referred to the central cornea, position 2 was nearest to the main wound, and position 3 was at the peripheral zone diagonal to the main wound. RESULTS: This study analyzed 96 eyes in the FLACS group and 110 eyes in the CPS group. Preoperatively, position 1 had lower ECD and CoV and higher Hex compared with the peripheral regions. FLACS patients had a significantly less phacoemulsification time and cumulative dissipated energy. At 1 month, FLACS patients showed a significantly smaller increase in corneal thickness at positions 1 and 2. At 3 months, FLACS patients had lower endothelial cell loss (ECL) at positions 1 and 3. ECL remained lower in FLACS patients at 6 months. The highest ECL was observed at position 2 in both groups and was progressive up to 6 months. CONCLUSIONS: After phacoemulsification, ECL varied in different corneal regions. At 3 months, the FLACS group exhibited significantly less ECL at the central cornea; however, the continued ECL at 6 months near the main wound suggested ongoing endothelial remodeling in the region.

Fusarium Keratitis in Taiwan: Molecular Identification, Antifungal Susceptibilities, and Clinical Features.

We performed molecular identification and antifungal susceptibilities of pathogens and investigated clinical features of 43 culture-proven Fusarium keratitis cases from 2015-2020 in Taiwan. The pathogens were identified by sequencing of their internal transcribed spacer regions of ribosomal DNA and translation elongation factor 1α gene; their antifungal susceptibilities (to seven agents) were determined by broth microdilution method. We also collected clinical data to compare the drug susceptibilities and clinical features of Fusarium solani species complex (FSSC) isolates with those of other Fusarium species complexes (non-FSSC). The FSSC accounted for 76.7% pathogens, among which F. falciforme (32.6%) and F. keratoplasticum (27.9%) were the most common species. Among clinically used antifungal agents, amphotericin B registered the lowest minimal inhibitory concentration (MIC), and the new azoles efinaconazole, lanoconazole and luliconazole, demonstrated even lower MICs against Fusarium species. The MICs of natamycin, voriconazole, chlorhexidine, lanoconazole, and luliconazole were higher for the FSSC than the non-FSSC, but no significant differences were noted in clinical outcomes, including corneal perforation and final visual acuity. In Taiwan, the FSSC was the most common complex in Fusarium keratitis; its MICs for five tested antifungal agents were higher than those of non-FSSC, but the clinical outcomes did not differ significantly.

Self-assembly of an antireflective moth-like structure using antibody-functionalized nanowires and nanopore arrays.

A novel framework to fabricate moth-like nanopillar arrays was proposed. In this scheme, nanowires were first cross-linked with anti-gold nanoparticle (GNP) antibodies and mixed with the nanopore array pre-deposited by GNP, which was then followed by centrifugation. An optimal success rate of 95% was finally obtained by choosing nanorods with an aspect ratio of 5:1 by modifying with 10 ng mL⁻¹ antibodies, and by inserting them into a pore array pre-deposited with 54.4 µM GNP. The nanopillar arrays thus fabricated showed high levels of antireflective efficiency across a broad wavelength. Here we demonstrate the assembly of nanowires and nanopores into nanopillar arrays by the assistance of antibody-antigen binding. The application of bio-nano-interaction provides an economic, time-saving, and throughput approach to manipulating objects on the nanoscale.

The Risks of Corneal Surface Damage in Aqueous-Deficient Dry Eye Disease: A 17-Year Population-Based Study in Taiwan.

PURPOSE: To investigate the epidemiologic characteristics and risk of corneal surface damage in patients with aqueous-deficient dry eye disease (DED) in Taiwan. DESIGN: Retrospective, population-based cohort study. METHODS: We used claims data in the Taiwan National Health Insurance Research Database from 1997 to 2013 of patients with DED, defined according to diagnoses, drug codes, and clinical follow-up. A comparison cohort without DED was selected through propensity score matching. The main outcome measures were corneal surface damage, including corneal erosion, corneal ulcers, or corneal scars. RESULTS: Patients with DED had a significantly higher rate of corneal surface damage (hazard ratio [HR]: 2.70; 95% confidence interval [CI] 2.38-3.06, P < .001), especially higher in patients aged <18 years (HR 6.66; 95% CI 3.58-12.41) than in older patients and in women (HR 2.98; 95% CI 2.57-3.46) than in men (HR 2.22; 95% CI 1.78-2.77), compared to those in the non-DED cohort. DED with diabetes mellitus (P = .002), rheumatoid arthritis (P = .029), or systemic lupus erythematosus (P = .005) was positively associated with corneal surface damage. The overall prevalence of DED was 7.85%, higher among women (10.49%) than men (4.92%), and increased with age (0.53%, 3.94%, 10.08%, and 20.72% for ages <18, 18-39, 40-64, and >65 years, respectively). The prevalence increased gradually during the study period. CONCLUSIONS: The younger age group (<18 years) had the highest risk of corneal surface damage in aqueous-deficient DED. Other predisposing factors included female sex, diabetes, and autoimmune diseases. To improve clinical care, special attention is required for patients with DED with these risk factors.

Using Slit-Lamp Images for Deep Learning-Based Identification of Bacterial and Fungal Keratitis: Model Development and Validation with Different Convolutional Neural Networks.

In this study, we aimed to develop a deep learning model for identifying bacterial keratitis (BK) and fungal keratitis (FK) by using slit-lamp images. We retrospectively collected slit-lamp images of patients with culture-proven microbial keratitis between 1 January 2010 and 31 December 2019 from two medical centers in Taiwan. We constructed a deep learning algorithm consisting of a segmentation model for cropping cornea images and a classification model that applies different convolutional neural networks (CNNs) to differentiate between FK and BK. The CNNs included DenseNet121, DenseNet161, DenseNet169, DenseNet201, EfficientNetB3, InceptionV3, ResNet101, and ResNet50. The model performance was evaluated and presented as the area under the curve (AUC) of the receiver operating characteristic curves. A gradient-weighted class activation mapping technique was used to plot the heat map of the model. By using 1330 images from 580 patients, the deep learning algorithm achieved the highest average accuracy of 80.0%. Using different CNNs, the diagnostic accuracy for BK ranged from 79.6% to 95.9%, and that for FK ranged from 26.3% to 65.8%. The CNN of DenseNet161 showed the best model performance, with an AUC of 0.85 for both BK and FK. The heat maps revealed that the model was able to identify the corneal infiltrations. The model showed a better diagnostic accuracy than the previously reported diagnostic performance of both general ophthalmologists and corneal specialists.

Filamentous Fungal Keratitis in Taiwan: Based on Molecular Diagnosis.

Purpose: To analyze the epidemiological pattern, demographics, risk factors, and treatment outcomes of filamentous fungal keratitis at a tertiary hospital in Taiwan. Methods: We recruited 65 patients (65 eyes) with culture-proven filamentous fungal keratitis who received diagnosis and treatment at Chang Gung Memorial Hospital between 2015 and 2018. All isolates were examined through conventional morphological identification and subjected to molecular identification with internal transcribed spacer sequencing. Data on patient demographics, predisposing factors, and treatment outcomes were collected. Results: In total, filamentous fungi belonged to 16 genera were identified. Fusarium spp. (29 cases [44.6%]) was the most commonly isolated organism overall, followed by Colletotrichum spp. and Purpureocillium linacinum (seven cases [10.8% for each]), and Aspergillus spp. (six cases [9.2%]). Some fungi that have not been regarded as human pathogens were also identified, such as Paracremonium and Phellinum. Among 52 (80%) patients with predisposing factors, 30 (46.2%) had trauma. The ulcers of 33 (50.8%) patients resolved with medical treatment only. Additionally, six patients (9.2%) had corneal perforation, and nine patients (13.9%) required therapeutic/destructive surgical interventions including therapeutic penetrating keratoplasty (seven patients) or evisceration (two patients). Only 16 patients (24.6%) had final visual acuity of 20/40 or better. Conclusions: Through molecular diagnosis, a high diversity of fungal pathogens was revealed along with an increasing incidence of Colletotrichumspp. and Purpureocilliumspp. in Taiwan. The most common risk factor for filamentous fungal keratitis was trauma. The visual outcomes were guarded. Translational Relevance: The molecular diagnosis provides insight into accurate identification, which affects the epidemiology and diversity of pathogens of filamentous fungal keratitis.

Risk of cancer in patients with iron deficiency anemia: a nationwide population-based study.

OBJECTIVE: This study evaluated the risk of cancer among patients with iron deficiency anemia (IDA) by using a nationwide population-based data set. METHOD: Patients newly diagnosed with IDA and without antecedent cancer between 2000 and 2010 were recruited from the Taiwan National Health Insurance Research Database. The standardized incidence ratios (SIRs) of cancer types among patients with IDA were calculated. RESULTS: Patients with IDA exhibited an increased overall cancer risk (SIR: 2.15). Subgroup analysis showed that patients of both sexes and in all age groups had an increased SIR. After we excluded patients diagnosed with cancer within the first and first 5 years of IDA diagnosis, the SIRs remained significantly elevated at 1.43 and 1.30, respectively. In addition, the risks of pancreatic (SIR: 2.31), kidney (SIR: 2.23), liver (SIR: 1.94), and bladder cancers (SIR: 1.74) remained significantly increased after exclusion of patients diagnosed with cancer within 5 years after IDA diagnosis. CONCLUSION: The overall cancer risk was significantly elevated among patients with IDA. After we excluded patients diagnosed with IDA and cancer within 1 and 5 years, the SIRs remained significantly elevated compared with those of the general population. The increased risk of cancer was not confined to gastrointestinal cancer when the SIRs of pancreatic, kidney, liver, and bladder cancers significantly increased after exclusion of patients diagnosed with IDA and cancer within the first 5 years. This finding may be caused by immune activities altered by IDA. Further study is necessary to determine the association between IDA and cancer risk.