Citrullus mucosospermus Extract Exerts Protective Effects against Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Steatohepatitis in Mice.

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Bioorthogonal non-canonical amino acid tagging to track transplanted human induced pluripotent stem cell-specific proteome.

BACKGROUND: Human induced pluripotent stem cells (hiPSCs) and their differentiated cell types have a great potential for tissue repair and regeneration. While the primary focus of using hiPSCs has historically been to regenerate damaged tissue, emerging studies have shown a more potent effect of hiPSC-derived paracrine factors on tissue regeneration. However, the precise contents of the transplanted hiPSC-derived cell secretome are ambiguous. This is mainly due to the lack of tools to distinguish cell-specific secretome from host-derived proteins in a complex tissue microenvironment in vivo. METHODS: In this study, we present the generation and characterization of a novel hiPSC line, L274G-hiPSC, expressing the murine mutant methionyl-tRNA synthetase, L274GMmMetRS, which can be used for tracking the cell specific proteome via biorthogonal non-canonical amino acid tagging (BONCAT). We assessed the trilineage differentiation potential of the L274G-hiPSCs in vitro and in vivo. Furthermore, we assessed the cell-specific proteome labelling in the L274G-hiPSC derived cardiomyocytes (L274G-hiPSC-CMs) in vitro following co-culture with wild type human umbilical vein derived endothelial cells and in vivo post transplantation in murine hearts. RESULTS: We demonstrated that the L274G-hiPSCs exhibit typical hiPSC characteristics and that we can efficiently track the cell-specific proteome in their differentiated progenies belonging to the three germ lineages, including L274G-hiPSC-CMs. Finally, we demonstrated cell-specific BONCAT in transplanted L274G-hiPSC-CMs. CONCLUSION: The novel L274G-hiPSC line can be used to study the cell-specific proteome of hiPSCs in vitro and in vivo, to delineate mechanisms underlying hiPSC-based cell therapies for a variety of regenerative medicine applications.

Clinical Staging of Prostaglandin-Associated Periorbitopathy Syndrome in Glaucoma: A Review from Asia.

PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.

Can Baseline Parapapillary Atrophy Morphology Predict Future Glaucoma Progression?- An OCT Glaucoma Imaging Study.

PURPOSE: To investigate glaucoma progression based on Optical Coherence Tomography (OCT) Guided Progression Analysis (GPA) according to baseline ß-zone parapapillary atrophy (PPA) morphology in glaucoma patients. DESIGN: Retrospective cohort study. METHODS: Patients over 20 years of age who had been diagnosed with primary open-angle glaucoma (POAG) at Seoul National University Hospital, Seoul, Korea between 2010 and 2020. This study included POAG patients with a minimum of 5 years of follow-up. We quantitatively measured the baseline ß-zone PPA parameters, classified ß-zone PPA morphology according to new classification standard we created and analyzed the corresponding GPA progression of the retinal nerve fiber layer (RNFL). RESULTS: A total of 210 patients with POAG (mean age: 53.8 years) were enrolled in the study. The mean follow-up period was 9.8 years. The average value of the baseline mean deviation in visual field perimetry was -2.48 dB. Longer radial extent and larger angular extent of ß-zone PPA were significantly associated with progression on GPA, as was the presence of disc hemorrhage. Among the 4 classified ß-zone PPA morphologies (Crescent type 1 & 2, Solar-eclipse type 1 & 2), the Solar-eclipse type 2 group showed the highest progression. A Kaplan-Meier survival analysis demonstrated significant differences among the 4 types. CONCLUSIONS: The larger the radial and angular extents of ß-zone PPA, the more progression that was shown on OCT GPA. Furthermore, significant differences in progression were noted based on the morphological type of ß-zone PPA. Our findings indicate that baseline ß-zone PPA parameters and morphology are valuable predictors of future glaucoma progression.

Efficacy and Safety of Surgical Peripheral Iridectomy, Goniosynechialysis, and Goniotomy for Advanced Primary Angle-closure Glaucoma without Cataract: One-year Results of a Multicenter Study.

PRCIS: The combination of surgical peripheral iridectomy, goniosynechialysis, and goniotomy is a safe and effective surgical approach for advanced primary angle-closure glaucoma without cataract. PURPOSE: To evaluate the efficacy and safety of surgical peripheral iridectomy (SPI), goniosynechialysis (GSL), and goniotomy (GT) in advanced primary angle-closure glaucoma (PACG) eyes without cataract. PATIENTS AND METHODS: A prospective multicenter observational study was performed for patients who underwent combined SPI, GSL, and GT for advanced PACG without cataract. Patients were assessed before and after the operation. Complete success was defined as achieving intraocular pressure (IOP) between 6-18 mm Hg with at least a 20% reduction compared to baseline, without the use of ocular hypotensive medications or reoperation. Qualified success adopted the same criteria but allowed medication use. Factors associated with surgical success were analyzed using logistic regression. RESULTS: A total of 61 eyes of 50 advanced PACG were included. All participants completed 12 months of follow-up. Thirty-six eyes (59.0%) achieved complete success, and 56 eyes (91.8%) achieved qualified success. Preoperative and postsurgical at 12 months mean IOPs were 29.7±7.7 and 16.1±4.8 mm Hg, respectively. The average number of ocular hypotensive medications decreased from 1.9 to 0.9 over 12 months. The primary complications included IOP spike (n=9), hyphema (n=7), and shallow anterior chamber (n=3). Regression analysis indicated that older age (odds ratio [OR]=1.09; P=0.043) was positively associated with complete success, while a mixed angle closure mechanism (OR=0.17; P=0.036) reduced success rate. CONCLUSIONS: The combination of SPI, GSL, and GT is a safe and effective surgical approach for advanced PACG without cataract. It has great potential as a first-line treatment option for these patients.

Age-related changes of intraocular pressure in Dutch belted rabbits.

This study investigated intraocular pressure (IOP) in Dutch belted rabbits using two different tonometers, rebound tonometry (TonoVet Plus; TVP) and a Tonopen (Tono-Pen AVIA Vet; TPA). Post-pubescent male Dutch belted rabbits aged 36 weeks (n = 10 animals) were used in the study. IOP measurements were conducted every 2 weeks for 22 weeks using TVP and TPA on both eyes of each rabbit. The average IOP measurements were compared by the paired Student's t-test. Pairwise Pearson's correlation coefficients and Bland-Altman statistics were used. The overall mean IOP measured with TPA was significantly higher than that with TVP (23.5 ± 4.9 vs. 21.8 ± 2.4 mmHg for the right eyes; P = 0.045, and 23.0 ± 4.7 vs. 21.5 ± 2.4 mmHg for the left eyes; P = 0.047). Both tonometers tended to show increased IOP readings with age, and positive correlations between IOP and age were observed with both TPA (r = 0.95, P < 0.001 for right eyes; r = 0.95, P < 0.001 for left eyes) and TVP (r = 0.91, P < 0.001 for right eyes; r = 0.64, P = 0.024 for left eyes). The average bias calculated by subtracting TPA from TVP was - 1.60 (95% confidence intervals - 1.927, - 1.281) mmHg. IOP in post-pubescent Dutch belted rabbits tended to increase with age throughout the 22 week study.

Long-term prognosis of acute primary angle closure in an east asian cohort.

PURPOSE: To provide an updated analysis of the long-term outcomes of patients with acute primary angle closure (APAC) and to investigate the risk factors for visual field (VF) loss progression. STUDY DESIGN: Retrospective, clinical cohort study METHODS: One hundred and forty-six APAC patients with a minimum of 1-year follow-up were included. The presenting features and the treatment utilized were recorded. The visual and intraocular pressure (IOP) outcomes were analyzed. The main outcome measures were the proportion of blindness and IOP at the final visit. A subset of patients with sufficient VF results was divided into a stable and progressive group based on mean deviation (MD) loss rate. Univariate and multivariate logistic regression analyses were performed to identify predictors of progression. RESULTS: Nine patients (6.2%) were blind, and 76.0% (111/146) had final decimal visual acuity greater than or equal to 0.5. All patients had normal final IOP, and 65.1% (95/146) were medication-free. 64.4% (94/146) underwent cataract surgery at a median 4 months after their APAC attack. The use of topical hypotensive medications (OR = 8.029, P = 0.012) was the only significant predictor of fast MD loss in the multivariate regression. CONCLUSIONS: The long-term outcomes of APAC in recent years have been more promising. All patients maintained normal IOP several years following their APAC attack, and fewer than half required hypotensive agents. The incidence of blindness was low. These findings suggest that current practice patterns in the management of APAC are beneficial.

Impact of peripheral anterior synechiae on the outcome of combined phacoemulsification, goniosynechialysis and goniotomy for primary angle-closure glaucoma and cataract: a multicenter observational study.

PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle-closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataract who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into three groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mmHg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred and four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery (P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the three groups (P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared to 180°≤PAS<270° (P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataract over one year period. However, the outcome was not correlated with preoperative extent of PAS. PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle-closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae.

Effects of sub-inhibitory concentrations of nafcillin, vancomycin, ciprofloxacin, and rifampin on biofilm formation of clinical methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class. IMPORTANCE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

3-O-Substituted Quercetin: an Antibiotic-Potentiating Agent against Multidrug-Resistant Gram-Negative Enterobacteriaceae through Simultaneous Inhibition of Efflux Pump and Broad-Spectrum Carbapenemases.

The discovery of safe and efficient inhibitors against efflux pumps as well as metallo-ß-lactamases (MBL) is one of the main challenges in the development of multidrug-resistant (MDR) reversal agents which can be utilized in the treatment of carbapenem-resistant Gram-negative bacteria. In this study, we have identified that introduction of an ethylene-linked sterically demanding group at the 3-OH position of the previously reported MDR reversal agent di-F-Q endows the resulting compounds with hereto unknown multitarget inhibitory activity against both efflux pumps and broad-spectrum ß-lactamases including difficult-to-inhibit MBLs. A molecular docking study of the multitarget inhibitors against efflux pump, as well as various classes of ß-lactamases, revealed that the 3-O-alkyl substituents occupy the novel binding sites in efflux pumps as well as carbapenemases. Not surprisingly, the multitarget inhibitors rescued the antibiotic activity of a carbapenem antibiotic, meropenem (MEM), in NDM-1 (New Delhi Metallo-ß-lactamase-1)-producing carbapenem-resistant Enterobacteriaceae (CRE), and they reduced MICs of MEM more than four-fold (synergistic effect) in 8-9 out of 14 clinical strains. The antibiotic-potentiating activity of the multitarget inhibitors was also demonstrated in CRE-infected mouse model. Taken together, these results suggest that combining inhibitory activity against two critical targets in MDR Gram-negative bacteria, efflux pumps, and ß-lactamases, in one molecule is possible, and the multitarget inhibitors may provide new avenues for the discovery of safe and efficient MDR reversal agents.

Long-Term Follow-Up of Myopic Glaucoma: Progression Rates and Associated Factors.

PRCIS: In the group of glaucoma patients with myopia, the more severe the degree of myopia, the faster the loss of visual acuity and central visual field defect. DESIGN: Longitudinal observational study. OBJECTIVE: To investigate the progression rate of myopic glaucoma and associated factors by long-term analysis of its clinical course. METHODS: Patients who had had at least 5 years of follow-up and a spherical equivalent of -0.5 diopters or less were included in this study. They were divided into 3 myopia groups according to myopic grade, namely mild myopia (-0.5 to -3.0 diopters), moderate myopia (-3.0 to -6.0 diopters), and high myopia (-6.0 diopters or more), and the clinical course, progression rate, and associated factors were compared among the groups and analyzed. RESULTS: A total of 121 eyes of 121 patients with glaucoma with myopia were included in the study. The average follow-up period was 10.4 ± 2.9 years. In the analysis of progression rate, the change rate of average retinal nerve fiber layer (RNFL) thickness (-0.75 µm/y in mild myopia, -0.82 µm/y in moderate myopia, -0.84 µm/y in high myopia) and the mean deviation change (-0.30 dB/y in mild myopia, -0.37 dB/y in moderate myopia, -0.39 dB/y in high myopia) both tended to be faster as the myopic grade increased. In a Kaplan-Meier survival analysis, the high myopia groups demonstrated a significantly faster VA loss (of more than 3 lines) and a higher incidence of newly developed central visual field defect (CVFD) than did the mild and moderate myopia groups. Longer axial length (odds ratio: 1.72, CI: 1.03-3.07, P = 0.047) and RNFL defect extending to the macula (odds ratio: 4.14, CI: 1.54-12.30, P = 0.007) were significantly associated with newly developed CVFD. CONCLUSIONS: In patients with myopic glaucoma, the higher the degree of myopia, the faster the rate of visual acuity loss and CVFD occurrence. Occurrence of CVFD was associated with longer axial length and widening of RNFLr defect to the macula.

Hemifield-based analysis of pattern electroretinography in normal subjects and patients with preperimetric glaucoma.

This prospective cross-sectional study investigated the visual function of preperimetric glaucoma (PPG) patients based on hemifield (HF) pattern electroretinogram (PERG) amplitudes. Thirty-two (32) normal subjects and 33 PPG patients were enrolled in control and PPG groups, respectively. All of the participants had undergone full ophthalmic examinations, including spectral-domain optical coherence tomography (SD-OCT), visual field (VF) examination and pattern electroretinography (PERG). The PERG parameters along with the HF ratios of SD-OCT and PERG were compared between the control and PPG groups. Pairwise Pearson's correlation coefficients and linear regression models were fitted to investigate the correlations. The PERG N95 amplitudes were significantly lower in the PPG group (P < 0.001). The smaller/larger HF N95 amplitude ratio of the PPG group was found to be smaller than that of the control group (0.73 ± 0.20 vs. 0.86 ± 0.12; P = 0.003) and showed positive correlations with affected HF average ganglion cell-inner plexiform layer (GCIPL) thickness (r = 0.377, P = 0.034) and with average GCIPL thickness (r = 0.341, P = 0.005). The smaller/larger HF N95 amplitude ratio did not significantly change with age (ß = - 0.005, P = 0.195), whereas the full-field N95 amplitude showed a negative correlation with age (ß = - 0.081, P < 0.001). HF analysis of PERG N95 amplitudes might be particularly useful for patients with early glaucoma.

Clinical Significance of Optic Disc Hemorrhage Size in Visual Field Progression in Glaucoma.

PURPOSE: To investigate the correlation between optic disc hemorrhage (DH) size and glaucoma progression. DESIGN: A retrospective observational cohort study METHODS:   SETTING: A single tertiary hospital in South Korea STUDY POPULATION: Two hundred and fifty (250) open-angle glaucoma (OAG) patients with DH. Participants were followed for 5 years or longer, with a minimum of 5 visual field (VF) tests. OBSERVATION PROCEDURE: The DH area was calculated by comparing the pixel numbers of the DH area with the disc area based on optical coherence tomography (OCT). For recurrent DH cases, we calculated the average DH area. DH size was classified as large or small based on the median value. Rates of mean deviation (MD) loss were determined using guided progression analysis (GPA). Univariable and multivariable regression analyses were performed to identify significant predictors of MD loss. MAIN OUTCOME MEASURES: DH size and longitudinal VF progression RESULTS: The mean follow-up period was 11.1 ± 3.6 years. The group with large DH showed faster global MD loss relative to the group with small DH (-0.51±0.48 dB/y vs -0.36 ± 0.42 dB/y, P = .01). In the multivariable model, mean DH size, maximum DH size, and initial MD were all significantly associated with the overall rate of MD loss (all P < .05). CONCLUSIONS: DH size was associated with the rate of VF deterioration. Eyes with larger DH showed more pronounced VF progression.

Potentiation of Antibiotic Activity of Aztreonam against Metallo-ß-Lactamase-Producing Multidrug-Resistant Pseudomonas aeruginosa by 3-O-Substituted Difluoroquercetin Derivatives.

The combination of aztreonam (ATM) and ceftazidime-avibactam (CAZ-AVI; CZA) has shown therapeutic potential against serine-ß-lactamase (SBL)- and metallo-ß-lactamase (MBL)-producing Enterobacterales. However, the ability of CZA to restore the antibiotic activity of ATM is severely limited in MBL-producing multidrug-resistant (MDR) Pseudomonas aeruginosa strains because of the myriad of intrinsic and acquired resistance mechanisms associated with this pathogen. We reasoned that the simultaneous inhibition of multiple targets associated with multidrug resistance mechanisms may potentiate the antibiotic activity of ATM against MBL-producing P. aeruginosa. During a search for the multitarget inhibitors through a molecular docking study, we discovered that di-F-Q, the previously reported efflux pump inhibitor of MDR P. aeruginosa, binds to the active sites of the efflux pump (MexB), as well as various ß-lactamases, and these sites are open to the 3-O-position of di-F-Q. The 3-O-substituted di-F-Q derivatives were thus synthesized and showed hereto unknown multitarget MDR inhibitory activity against various ATM-hydrolyzing ß-lactamases (AmpC, KPC, and New Delhi metallo-ß-lactamase (NDM)) and the efflux pump of P. aeruginosa, presumably by forming additional hydrophobic contacts with the targets. The multitarget MDR inhibitor 27 effectively potentiated the antimicrobial activity of ATM and reduced the MIC of ATM more than four-fold in 19 out of 21 MBL-producing P. aeruginosa clinical strains, including the NDM-producing strains which were highly resistant to various combinations of ATM with ß-lactamase inhibitors and/or efflux pump inhibitors. Our findings suggest that the simultaneous inhibition of multiple MDR targets might provide new avenues for the discovery of safe and efficient MDR reversal agents which can be used in combination with ATM against MBL-producing MDR P. aeruginosa.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Intraocular pressure reduction and progression of highly myopic glaucoma: a 12-year follow-up cohort study.

AIMS: To investigate any association between intraocular pressure (IOP) reduction amount and open-angle glaucoma (OAG) progression in highly myopic eyes and to determine the associated risk factors. METHODS: One hundred and thirty-one (131) eyes of 131 patients with highly myopic OAG, all of whom had received topical medications and been followed for 5 years or longer, were enrolled. Based on the IOP reduction percentage, patients were categorised into tertile groups, and subsequently, the upper-tertile and lower-tertile groups were compared for the cumulative probability of glaucoma progression. Kaplan-Meier survival analysis and log-rank testing were applied in the comparison, and multivariate analysis with Cox's proportional hazard model, additionally, was performed to identify progression risk factors. RESULTS: Throughout the average 11.6±4.4 year follow-up on the 131 eyes (mean age, 41.2 years at initial visit; baseline IOP, 16.4 mm Hg), 72 eyes (55.0%) showed glaucoma progression. The upper-tertile group (IOP reduction percentage>23.7%) showed a high cumulative probability of non-progression relative to the lower-tertile group (IOP reduction percentage<11.0%; p=0.034), according to the Kaplan-Meier analysis. Presence of disc haemorrhage (DH; HR=2.189; p=0.032) was determined by the multivariate Cox's proportional hazard model to be significantly associated with glaucoma progression. For progressors, the average rate of retinal nerve fibre layer thickness thinning was -0.88±0.74 µm/year, while the MD change was -0.42±0.36 dB/year. CONCLUSIONS: Glaucoma progression is associated with amount of IOP reduction by topical medications in highly myopic eyes, and DH occurrence is a glaucoma progression risk factor.

Longitudinal evaluation of advanced glaucoma: ten year follow-up cohort study.

This study focused on patients with advanced open-angle glaucoma (OAG) and aimed to identify key factors for monitoring them. We included 127 such patients who were followed for seven years or more, undergoing annual ophthalmic examinations. Glaucoma progression was defined as a deterioration in either structure or function. The progression rates and risk factors were evaluated. The patients were divided into upper- and lower-half subgroups based on the reduction in intraocular pressure (IOP) from the baseline. Over an 11-year period, glaucoma progression was detected in 59 eyes (46.5%). The rate of change in mean deviation (MD) was - 0.43 dB/year for the entire population; - 0.67 dB/year for progressors; and - 0.20 dB/year for non-progressors. Hypertension and disc hemorrhage (DH) were more common in progressors compared to non-progressors (45.8 vs. 23.5%, 11.9 vs. 1.5%; P = 0.008 and P = 0.016). Multivariate Cox's proportional hazard model revealed that the presence of DH and a better baseline MD were associated with glaucoma progression. Additionally, patients with a higher percentage reduction in IOP (> 20.94%) had a lower risk of progression compared to those with less reduction. Inadequate IOP reduction, better baseline MD, presence of DH, and lower central corneal thickness were identified as risk factors for progression in advanced OAG patients.

Incidence of and Risk Factors for Fellow-Eye Involvement in Sturge-Weber Syndrome Children With Unilateral Glaucoma.

PRCIS: Among children with unilateral glaucoma associated with Sturge-Weber syndrome (SWS), 7 of 47 demonstrated involvement in the fellow eye, and that group had had earlier first-eye surgery relative to the noninvolvement group. PURPOSE: The aim of this study was to determine the incidence of and risk factors for fellow-eye involvement in children with unilateral SWS-associated glaucoma. MATERIALS AND METHODS: Children diagnosed with a unilateral facial port-wine stain and ipsilateral glaucoma before the age of 5 and followed up for at least 5 years were enrolled. The incidence rates of fellow-eye glaucoma involvement were estimated per 100 person-years, and factors associated with a higher incidence of fellow-eye involvement were investigated. RESULTS: A total of 47 children [24 (51.1%) girls] with unilateral SWS-associated glaucoma were included. All of them had facial port-wine stain involving ophthalmic division of the trigeminal nerve, and 18 (38.3%) had neurological comorbidities. The mean age at glaucoma diagnosis was 0.8±1.2 years [range, 0.08 (1 mo)-4.0 y]. Over a median follow-up of 8.4 years, glaucoma was diagnosed in the fellow eye of 7 of the children (14.9%; incidence rate of 1.8 per 100 person-years), 6 of whom were girls ( P =0.097) and 5 of whom were diagnosed before the age of 4 years ( P =0.508). The fellow-eye-involvement group showed significantly higher mean follow-up intraocular pressure in the fellow eye, older age at first-eye surgery (both P <0.005), and higher frequency of choroidal hemangioma both at first onset and in fellow eyes ( P =0.026 and 0.019, respectively). CONCLUSIONS: In this cohort of SWS children diagnosed with unilateral glaucoma, the risk of fellow-eye involvement was higher in girls, within the first 4 years, and in cases with choroidal hemangioma. The fellow-eye-involved children underwent surgery on the first eye earlier than those without fellow-eye involvement.