COVID-19 pandemic and trends in clinical outcomes and medication use for patients with established atrial fibrillation: A nationwide analysis of claims data.

Study objective: The COVID-19 pandemic disrupted multiple aspects of the health care system, including the diagnosis and control of chronic conditions. This study aimed to quantify pandemic-related changes in the rates of clinical events among patients with atrial fibrillation (AF). Design/setting/participants: In this retrospective cohort study, we identified individuals with established AF at any time before 2019 using de-identified Optum's Clinformatics® Data Mart, and followed them from 3/18/2019 to death, or disenrollment, or the end of the study (09/30/2021). Main outcome: Rates of clinical event, including all-cause hospitalization, ischemic stroke, and bleeding. We constructed interrupted time series to test changes in outcomes after the onset of the COVID-19 pandemic (3/11/2020, date of pandemic declaration). We then identified the first month after the start of the pandemic in which outcomes returned to pre-pandemic levels. Results: A total of 561,758 patients, with a mean age of 77 ± 9.9 years, were included in the study. The monthly incidence rate of all-cause hospitalization decreased from 2.8 % in the period immediately before the pandemic declaration to 1.7 % in the period immediately after, with p-value for level change<0.001. The rate of new ischemic stroke diagnoses decreased from 0.28 % in the period immediately before pandemic declaration to 0.20 % in the period immediately after, and the rate of major bleeding diagnoses from 0.81 % to 0.59 %, both p-values for level change<0.01. The incidence rate of ischemic stroke and bleeding events returned to pre-pandemic levels in October and November 2020, respectively. Conclusions: The COVID-19 pandemic was associated with a decrease in health care visits for ischemic stroke and bleeding in a nationwide cohort of patients with established AF.

Preparation of RDX/F2311/Fe2O3/Al Composite Hollow Microspheres by Electrospray and Synergistic Energy Release during Combustion between Components.

Nanothermites and high-energy explosives have significantly improved the performance of high-energy composites and have broad application prospects. Therefore, in this study, RDX/F2311/Fe2O3/Al composite hollow microspheres were successfully prepared utilizing the electrospray method using F2311 as a binder between components. The results show that the combustion time of the composite hollow microspheres is shortened from 2400 ms to 950 ms, the combustion process is more stable, and the energy release is more concentrated. The H50 of the composite hollow microspheres increased from 14.49 cm to 24.57 cm, the explosion percentage decreased from 84% to 72%, and the sensitivity of the composite samples decreased significantly. This is mainly the result of the combination of homogeneous composition and synergistic reactions. The combustion results show that F2311 as a binder affects the tightness of the contact between the components. By adjusting its content, the combustion time and the intensity of the combustion of the composite microspheres can be adjusted, which provides a feasible direction for its practical application.

CorNet: Autonomous feature learning in raw Corvis ST data for keratoconus diagnosis via residual CNN approach.

PURPOSE: To ascertain whether the integration of raw Corvis ST data with an end-to-end CNN can enhance the diagnosis of keratoconus (KC). METHOD: The Corvis ST is a non-contact device for in vivo measurement of corneal biomechanics. The CorNet was trained and validated on a dataset consisting of 1786 Corvis ST raw data from 1112 normal eyes and 674 KC eyes. Each raw data consists of the anterior and posterior corneal surface elevation during air-puff induced dynamic deformation. The architecture of CorNet utilizes four ResNet-inspired convolutional structures that employ 1 × 1 convolution in identity mapping. Gradient-weighted Class Activation Mapping (Grad-CAM) was adopted to visualize the attention allocation to diagnostic areas. Discriminative performance was assessed using metrics including the AUC of ROC curve, sensitivity, specificity, precision, accuracy, and F1 score. RESULTS: CorNet demonstrated outstanding performance in distinguishing KC from normal eyes, achieving an AUC of 0.971 (sensitivity: 92.49%, specificity: 91.54%) in the validation set, outperforming the best existing Corvis ST parameters, namely the Corvis Biomechanical Index (CBI) with an AUC of 0.947, and its updated version for Chinese populations (cCBI) with an AUC of 0.963. Though the ROC curve analysis showed no significant difference between CorNet and cCBI (p = 0.295), it indicated a notable difference between CorNet and CBI (p = 0.011). The Grad-CAM visualizations highlighted the significance of corneal deformation data during the loading phase rather than the unloading phase for KC diagnosis. CONCLUSION: This study proposed an end-to-end CNN approach utilizing raw biomechanical data by Corvis ST for KC detection, showing effectiveness comparable to or surpassing existing parameters provided by Corvis ST. The CorNet, autonomously learning comprehensive temporal and spatial features, demonstrated a promising performance for advancing KC diagnosis in ophthalmology.

Mendelian Randomisation Analysis of Causal Association between Lifestyle, Health Factors, and Keratoconus.

Keratoconus (KC), a leading cause of vision impairment, has an unclear aetiology. This study used Mendelian randomization (MR) to explore the causal links between various factors (smoking, asthma, Down syndrome, inflammatory bowel disease, atopic dermatitis, and serum 25-hydroxyvitamin D levels) and KC. A two-sample MR design, grounded in genome-wide association study (GWAS) summary statistics, was adopted using data from FinnGen, UK Biobank, and other GWAS-related articles. The inverse-variance weighted (IVW) method was employed, complemented by the Wald ratio method for factors with only one single-nucleotide polymorphism (SNP). Sensitivity and stability were assessed through Cochrane's Q test, the MR-Egger intercept test, MR-PRESSO outlier test, and the leave-one-out analysis. The IVW results for the ORA (Ocular Response Analyzer) biomechanical parameters indicated significant associations between tobacco smoking (CH: p < 0.001; CRF: p = 0.009) and inflammatory bowel disease (CH: p = 0.032; CRF: p = 0.001) and corneal biomechanics. The Wald ratio method showed tobacco smoking was associated with a lower risk of KC (p = 0.024). Conversely, asthma (p = 0.009), atopic dermatitis (p = 0.012), inflammatory bowel disease (p = 0.017), and serum 25-hydroxyvitamin D levels (p = 0.039) were associated with a higher risk of KC by IVW, and the same applied to Down syndrome (p = 0.004) using the Wald ratio. These results underscore the role of corneal biomechanics as potential mediators in KC risk, warranting further investigation using Corvis ST and Brillouin microscopy. The findings emphasise the importance of timely screening for specific populations in KC prevention and management.

Geographic variation and racial disparities in adoption of newer glucose-lowering drugs with cardiovascular benefits among US Medicare beneficiaries with type 2 diabetes.

BACKGROUND: Prior studies have shown disparities in the uptake of cardioprotective newer glucose-lowering drugs (GLDs), including sodium-glucose cotranwsporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1a). This study aimed to characterize geographic variation in the initiation of newer GLDs and the geographic variation in the disparities in initiating these medications. METHODS: Using 2017-2018 claims data from a 15% random nationwide sample of Medicare Part D beneficiaries, we identified individuals diagnosed with type 2 diabetes (T2D), who had ≥1 GLD prescriptions, and did not use SGLT2i or GLP1a in the year prior to the index date,1/1/2018. Patients were followed up for a year. The cohort was spatiotemporally linked to Dartmouth hospital-referral regions (HRRs), with each patient assigned to 1 of 306 HRRs. We performed multivariable Poisson regression to estimate adjusted initiation rates, and multivariable logistic regression to assess racial disparities in each HRR. RESULTS: Among 795,469 individuals with T2D included in the analyses, the mean (SD) age was 73 (10) y, 53.3% were women, 12.2% were non-Hispanic Black, and 7.2% initiated a newer GLD in the follow-up year. In the adjusted model including clinical factors, compared to non-Hispanic White patients, non-Hispanic Black (initiation rate ratio, IRR [95% CI]: 0.66 [0.64-0.68]), American Indian/Alaska Native (0.74 [0.66-0.82]), Hispanic (0.85 [0.82-0.87]), and Asian/Pacific islander (0.94 [0.89-0.98]) patients were less likely to initiate newer GLDs. Significant geographic variation was observed across HRRs, with an initiation rate spanning 2.7%-13.6%. CONCLUSIONS: This study uncovered substantial geographic variation and the racial disparities in initiating newer GLDs.

COVID-19 pandemic and initiation of treatment for atrial fibrillation: a nationwide analysis of claims data.

BACKGROUND: The COVID-19 pandemic profoundly disrupted the delivery of medical care. It remains unclear whether individuals diagnosed with new onset disease during the pandemic were less likely to initiate treatments after diagnosis. We sought to evaluate changes in the treatment initiation of patients newly diagnosed with atrial fibrillation (AF) after the onset of the COVID-19 pandemic. METHODS: In this retrospective cohort study, we identified individuals with incident AF from 01/01/2016-09/30/2021 using Optum's de-identified Clinformatics® Data Mart Database. The primary outcome was initiation of oral anticoagulation (OAC) within 30 days of AF diagnosis. Secondary outcomes included initiation of OAC within 180 days of diagnosis, initiation of warfarin, direct oral anticoagulants (DOACs), rhythm control medications and electrical cardioversion within 30 days of diagnosis. We constructed interrupted time series analyses to examine changes in the outcomes following the onset of the pandemic. RESULTS: A total of 573,524 patients (age 73.0 ± 10.9 years) were included in the study. There were no significant changes in the initiation of OAC, DOAC, and rhythm control medications associated with the onset of the pandemic. There was a significant decrease in initiation of electrical cardioversion associated with the onset of the pandemic. The rate of electronic cardioversion within 30 days of diagnosis decreased by 4.9% per 1,000 patients after the onset of the pandemic and decreased by about 35% in April 2020, compared to April 2019, from 5.53% to 3.58%. CONCLUSION: The COVID-19 pandemic did not affect the OAC initiation within 30 days of AF diagnosis but was associated with a decline in the provision of procedures for patients newly diagnosed with AF.

A protocol for a single center, randomized, controlled trial comparing the clinical efficacy of 3% diquafosol and 0.1% hyaluronic acid in diabetic patients with dry eye disease.

BACKGROUND: The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. METHODS: This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS (n = 101) and HA (n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. TRIAL REGISTRATION: ClinicalTrials.govNCT05682547. Registered on December 05, 2022.

Effects of Diquafosol Sodium Ophthalmic Solution on Tear Film Matrix Metallopeptidase-9 and Corneal Nerve Density in Patients with Type 2 Diabetic Dry Eye.

Purpose: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED's pathology. This preliminary short-term study aimed to evaluate the effects of 3% Diquafosol Sodium ophthalmic solution (DQS) on ocular surface inflammation and corneal nerve density in diabetic dry eye (DDE) patients. Methods: In this perspective, participants used 1 drop of 3% DQS (Diquas; Santen Pharmaceutical Co., Ltd., Osaka, Japan) 6 times daily for 8 weeks. Non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctival hyperemia [redness score (RS)], corneoconjunctival staining (CFS), corneal sensitivity (CS), Meibomian gland quality (MGQ) and Meibomian gland expressibility (MGEx), corneal nerve fiber density (CNFD), and Standard Patient Evaluation Eye Dryness (SPEED) questionnaire were assessed at baseline, at weeks 4, and up to 8 weeks. Matrix metalloproteinase-9 (MMP-9) of tear samples was measured at baseline and weeks 8. Results: The mean age was 61.27 ± 11.68 years. At baseline NITBUT = 5.89 ± 2.81 s, tear meniscus height = 0.17 ± 0.05 mm, TFLL = 2.74 ± 0.51, CFS = 4.35 ± 0.68, CS = 53.83 ± 9.63 mm, MMP-9 = 49.10 ± 10.42 ng/mL, RS = 1.65 ± 0.44, MGEx = 1.85 ± 0.72, MGQ = 2.65 ± 0.50, CNFD = 20.36 ± 8.20 no./mm2, and SPEED = 12.62 ± 3.91. At week 4, significant improvements were found in all parameters except RS (1.59 ± 0.46, P = 0.172) and CNFD (21.46 ± 8.41, P = 0.163). Finally, at week 8, all parameters had significant improvements. Conclusion: Preliminary short-term findings suggest that treatment of DDE patients with DQS was found to be safe and efficacious in improving dry eye parameters. In addition, inflammatory marker and corneal nerve density were significantly improved. This study was registered with ClinicalTrials.gov (NCT05193331).

Individual and social determinants of adherence to sodium-glucose cotransporter 2 inhibitor therapy: A trajectory analysis.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are known to improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). Understanding the longitudinal patterns of adherence and the associated predictors is critical to addressing the suboptimal use of this outcome-improving treatment. OBJECTIVE: To characterize the distinct trajectories of adherence to SGLT2is in patients with T2D and to identify patient characteristics and social determinants of health (SDOHs) associated with SGLT2i adherence. METHODS: In this retrospective cohort study, we identified patients with T2D who initiated and filled at least 1 SGLT2i prescription according to 2012-2016 national Medicare claims data. The monthly proportion of days covered with SGLT2is for each patient was incorporated into group-based trajectory models to identify groups with similar adherence patterns. A multinomial logistic regression model was constructed to examine the association between patient characteristics and group membership. In addition, the association between context-specific SDOHs (eg, neighborhood median income and neighborhood employment rate) and adherence to an SGLT2i regimen was explored in both the overall cohort and the racial and ethnic subgroups. RESULTS: The final sample comprised 6,719 patients with T2D. Four trajectories of SGLT2i adherence were identified: continuously adherent users (49.6%), early discontinuers (27.5%), late discontinuers (14.5%), and intermediately adherent users (8.4%). Patient age, sex, race, diabetes duration, and Medicaid eligibility were significantly associated with trajectory group membership. Areas with a higher unemployment rate, lower income level, lower high school education rate, worse nutrition environment, fewer health care facilities, and greater Area Deprivation Index scores were found to be associated with low adherence to SGLT2is. CONCLUSIONS: Four distinct trajectories of adherence to SGLT2is were identified, with only half of the patients remaining continuously adherent to their treatment regimen during the first year after initiation. Several contextual SDOHs were associated with suboptimal adherence to SGLT2is.

Relationship between ocular surface pain and corneal nerve loss in dry eye diabetics: a cross-sectional study in Shenyang, China.

BACKGROUND: Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED pathology. OBJECTIVE: To investigate the potential relationship between corneal nerve loss and ocular pain among diabetic patients with dry eye (DE). DESIGN: A cross-sectional study. SETTING: He Eye Specialist Hospital, Shenyang, China. PARTICIPANTS: This study recruited 124 eyes of 62 diabetic patients diagnosed with DED between August and October 2022. MAIN OUTCOME MEASURES: Best-corrected visual acuity, intraocular pressure, non-invasive tear breakup time, tear meniscus height, tear film lipid layer, conjunctival hyperaemia (redness score), conjunctivocorneal epithelial staining (CS score), central corneal sensitivity and vitro confocal corneal microscopy was assessed in all subjects. The Ocular Surface Disease Index Questionnaire assessed DE symptoms and ocular pain. RESULTS: The study's final analysis included 26 patients (52 eyes) without ocular pain and 36 patients (72 eyes) with ocular pain. The corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) in patients with ocular pain were significantly lower than those without (p<0.001, p=0.004, and p<0.001, respectively). CNFD, CNBD and CNFL negatively correlated with ocular pain (r=-0.385, r=-0.260, r=-0.358, respectively). Moreover, CNFD, CNBD and CNFL have a significant (p<0.05) positive correlation with corneal sensitivity (r=0.523, r=0.330, r=0.421, respectively). CONCLUSIONS: Corneal nerve loss was associated with ocular pain and decreased corneal sensitivity in diabetic patients with DE. Further studies into the neurological role of ocular surface diseases can elaborate diagnostics, prognosis and treatment of diabetic patients with DE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05193331).

The Combined Impact of Intense Pulsed Light Combined and 3% Diquafosol Ophthalmic Solution on Evaporative Dry Eye: A Randomized Control Study.

INTRODUCTION: The primary objective of this study is to assess whether the combination of intense pulsed light (IPL) with 3% diquafosol (DQS) ophthalmic solution is more effective than intense pulsed light in alleviating signs and symptoms of dry eye disease (DED). METHODS: This randomized study included 66 participants with evaporative dry eye (EDE) who received IPL + DQS therapy (n = 44 eyes), IPL therapy (n = 44 eyes), or sham therapy (n = 44 eyes). All participants were examined at baseline (D0), day 14 (D14), and day 28 (D28) for non-invasive break-up time (NITBUT), tear-film lipid layer (TFLL), corneal conjunctival staining (CS), meibomian gland quality (MGQ), meibomian gland expression (MGEx), and ocular surface disease index (OSDI). RESULTS: At day 28, comparison among the IPL + DQS therapy, IPL therapy, and sham therapy found significant differences in the mean NITBUT (12.03 ± 1.27 versus 10.47 ± 3.48 versus 4.57 ± 0.46; p < 0.001), TFLL (2.09 ± 0.29 versus 2.27 ± 0.45 versus 2.89 ± 0.65; p < 0.001), CS (1.43 ± 0.82 versus 1.93 ± 1.32 versus 3.52 ± 1.00; p < 0.001), MGQ (1.55 ± 0.66 versus 1.91 ± 0.77 versus 2.66 ± 0.53; p < 0.001), MGEx (1.27 ± 0.45 versus 1.75 ± 0.44 versus 2.41 ± 0.50; p < 0.001), and OSDI score (19.36 ± 7.01 versus 24.77 ± 4.68 versus 42.61 ± 7.49; p < 0.001); significant improvements in NITBUT, TFLL, CS, MGQ, MGEx, and OSDI were found in the IPL + DQS therapy and IPL therapy, while the sham therapy had no significant improvements. CONCLUSION: Combining 3% diquafosol ophthalmic solution with intense pulsed light was superior to IPL therapy alone in relieving the signs and symptoms of patients with severe evaporative DED. TRIAL REGISTRATION: Clinical Trials Identifier: NCT05694026.

Protocol for a parallel assignment prospective, randomised, comparative trial to evaluate the safety and efficacy of intense pulsed light (IPL) combined with 3% diquafosol (DQS) ophthalmic solution in dry eye syndrome.

INTRODUCTION: Evaporative dry eye (EDE) is common and can lead to ocular pain, decreased visual quality and reduced quality of life. Intense pulsed light (IPL) and 3% diquafosol ophthalmic solution have been found to be beneficial in reducing signs and symptoms of dry eye. METHODS AND ANALYSIS: A randomised clinical trial will be performed at He Eye Specialist Hospital in Shenyang. 360 dry eye disease patients will be equally divided randomly into the IPL group, DQS group (3% diquafosol ophthalmic solution eye-drops) and IPL+group (IPL combined with 3% diquafosol eye-drops). All groups will be followed up for 4 weeks. The primary outcome measures will be the non-invasive tear break-up time and the Ocular Surface Disease Index change from the baseline. The secondary outcome measures willincludeconjunctival and cornea staining with fluorescein and lissamine, meibomian gland function and secretion quality, tear film lipid layer score, tear meniscus height, conjunctival hyperemia (redness score) changes . Adverse events also will be monitored and documented. DISCUSSION: This study aimed to assess whether the combination of IPL with 3% diquafosol ophthalmic solution (study group), IPL+ (study group), is more effective than IPL (active control group) or DQS (active control group) in participants with EDE. ETHICS AND DISSEMINATION: Management of dry eye with IPL combined with 3% diquafosol ophthalmic solution, registered on 23 January 2023. Ethics approval number: IRB (2022) K029.01. The study's findings will be shared regardless of the effect's direction. TRIAL REGISTRATION NUMBER: NCT05694026.

Preparation of quasi-core/shell structured composite energetic materials to improve combustion performance.

Composite explosives with fast reaction rate, high energy release efficiency, and remarkable combustion performance can be obtained by the interaction between homogeneous energetic materials and heterogeneous energetic materials and have broad application prospects. However, ordinary physical mixtures can easily cause separation between the components in the preparation process, which is not conducive to reflecting the advantages of composite materials. In this study, high-energy composite structured explosives with RDX modified by polydopamine as the core and PTFE/Al as the shell were prepared using a simple ultrasonic method. The study of morphology, thermal decomposition, heat release, and combustion performance demonstrated that the quasi-core/shell structured samples have higher exothermic energy, faster combustion rate, more stable combustion characteristics, and lower mechanical sensitivity than the physical mixture.

In-vivo high-speed biomechanical imaging of the cornea using Corvis ST and digital image correlation.

In-vivo corneal biomechanical characterization has gained significant clinical relevance in ophthalmology, especially in the early diagnosis of eye disorders and diseases (e.g. keratoconus). In clinical medicine, the air-puff-based tonometers such as Ocular Response Analyzer (ORA) and Corvis ST have been used in the in-vivo biomechanical testing. In the test, the high-speed dynamic deformation of the cornea under air-puff excitation is analyzed to identify the abnormities in the morphological and biomechanical properties of the cornea. While most existing measurements reflect the overall corneal biomechanical properties, in-vivo high-speed strain and strain rate fields at the tissue level have not been assessed. In this study, 20 subjects were classified into two different groups: the normal (NORM, N = 10) group and the keratoconus (KC, N = 10) group. Image sequences of the horizontal cross-section of the human cornea under air puff were captured by the Corvis ST tonometer. The macroscale mechanical response of the cornea was determined through image analysis. The high-speed evolution of full-field corneal displacement, strain, velocity, and strain rate was reconstructed using the incremental digital image correlation (DIC) approach. Differences in the parameters between the NORM and KC groups were statistically analyzed and compared. Statistical results indicated that compared with the NORM group, the KC corneas absorbed more energy (KC: 8.98 ± 2.76 mN mm; NORM: 4.79 ± 0.62 mN mm; p-value <0.001) with smaller tangent stiffness (KC: 22.49 ± 2.62 mN/mm; NORM: 24.52 ± 3.20 mN/mm; p-value = 0.15) and larger maximum deflection (KC: 0.99 ± 0.07 mN/mm; NORM: 0.92 ± 0.06 mN/mm; p-value <0.05) on the macro scale. Further, we also observed that The maximum displacement (KC: 1.17 ± 0.06 mm; NORM: 1.06 ± 0.07 mm; p-value <0.005), velocity (KC: 236 ± 29 mm/s; NORM: 203 ± 17 mm/s; p-value <0.01), shear strain (KC: 24.43 ± 2.59%; NORM: 20.26 ± 1.54%; p-value <0.001), and shear strain rate (KC: 69.74 ± 11.99 s-1; NORM: 54.84 ± 3.03 s-1; p-value <0.005) in the KC group significantly increased at the tissue level. This is the first time that the incremental DIC method was applied to the in-vivo high-speed corneal deformation measurement in combination with the Corvis ST tonometer. Through the image registration using incremental DIC analysis, spatiotemporal dynamic strain/strain rate maps of the cornea can be estimated at the tissue level. This is constructive for the clinical recognition and diagnosis of keratoconus at a more underlying level.

Managing Severe Evaporative Dry Eye with Intense Pulsed Light Therapy.

INTRODUCTION: This study assessed the efficacy and safety of intense pulsed light (IPL) therapy in participants with severe evaporative dry eye disease (DED). METHODS: This randomized, controlled, single-center study included 49 adult participants (≥ 18 years) with severe evaporative DED who received either IPL therapy (n = 56 eyes) or sham therapy (n = 42 eyes) three times. The primary efficacy parameters were ocular surface disease index (OSDI) score, non-invasive tear breakup time (NITBUT), tear film lipid layer (TFLL), conjunctivocorneal staining score (CS), MG Score, meibomian gland (MG) quality, and MG expression score. RESULTS: The mean ages for the IPL group and the control group were 28.05 ± 3.41 years (57.1% female) and 28.14 ± 3.53 years (52.4% female), respectively. Comparison between the IPL group and the control group found significant differences in the mean OSDI score (22.16 ± 6.08 vs. 42.38 ± 6.60; P < 00.01), NITBUT (6.27 ± 0.84 vs. 3.86 ± 0.68; P < 0.001), TFLL (2.14 ± 0.44 vs. 3.45 ± 0.50; P < 0.001), MG Score (1.34 ± 0.55 vs. 1.88 ± 0.33; P < 0.001), MG quality (1.59 ± 0.07 vs. 2.67 ± 0.08), and MG expression (1.54 ± 0.57 vs. 2.45 ± 0.55) at 12 weeks follow-up; however, there was no significant difference in CS (3.32 ± 1.11 vs. 3.74 ± 1.04; P = 0.063). CONCLUSION: The findings suggest that IPL therapy is clinically beneficial in ameliorating the signs and symptoms of severe evaporative dry eye disease.

Platelet Internalization Mediates Ferroptosis in Myocardial Infarction.

BACKGROUND: Myocardial cell death is the hallmark of myocardial infarction. In the process of myocardial injury, platelets contribute to the pathogenesis by triggering intense inflammatory responses. Yet, it is still unclear if platelets regulate cardiomyocyte death directly, thereby exacerbating myocardial injury in myocardial infarction. METHODS: We describe a mechanism underlying the correlative association between platelets accumulation and myocardial cell death by using myocardial infarction mouse model and patient specimens. RESULTS: Myocardial infarction induces platelets internalization, resulting in the release of miR-223-3p, a platelet-enriched miRNA. By targeting the ACSL3, miR-223-3p delivered by internalized platelets cause the reduction of stearic acid-phosphatidylcholine in cardiomyocytes. The presence of stearic acid-phosphatidylcholine protects cardiomyocytes against ferroptosis. CONCLUSIONS: Our work reveals a novel mechanism of platelet-mediated myocardial injury, highlighting antiplatelet therapies could potentially represent a multimechanism treatment of myocardial infarction, and implying ferroptosis being considered as novel target for therapeutics.

Glutathione prevents high glucose-induced pancreatic fibrosis by suppressing pancreatic stellate cell activation via the ROS/TGFß/SMAD pathway.

The activation of pancreatic stellate cells (PSCs) is the key mechanism of pancreatic fibrosis, which can lead to ß-cell failure. Oxidative stress is an important risk factor for PSC activation. There is no direct evidence proving if administration of glutathione can inhibit fibrosis and ß-cell failure. To explore the role of glutathione in pancreatic fibrosis and ß-cell failure induced by hyperglycaemia, we established a rat model of pancreatic fibrosis and ß-cell failure. The model was founded through long-term oscillating glucose (LOsG) intake and the setup of a sham group and a glutathione intervention group. In vitro, rat PSCs were treated with low glucose, high glucose, or high glucose plus glutathione to explore the mechanism of high glucose-induced PSC activation and the downstream effects of glutathione. Compared with sham rats, LOsG-treated rats had higher reactive oxygen species (ROS) levels in peripheral leukocytes and pancreatic tissue while TGFß signalling was upregulated. In addition, as the number of PSCs and pancreatic fibrosis increased, ß-cell function was significantly impaired. Glutathione evidently inhibited the upregulation of TGFß signalling and several unfavourable outcomes caused by LOsG. In vitro treatment of high glucose for 72 h resulted in higher ROS accumulation and potentiated TGFß pathway activation in PSCs. PSCs showed myofibroblast phenotype transformation with upregulation of α-SMA expression and increased cell proliferation and migration. Treatment with either glutathione or TGFß pathway inhibitors alleviated these changes. Together, our findings suggest that glutathione can inhibit PSC activation-induced pancreatic fibrosis via blocking ROS/TGFß/SMAD signalling in vivo and in vitro.

Identifying Patients at Risk of Acute Kidney Injury Among Medicare Beneficiaries With Type 2 Diabetes Initiating SGLT2 Inhibitors: A Machine Learning Approach.

Introduction: To predict acute kidney injury (AKI) risk in patients with type 2 diabetes (T2D) prescribed sodium-glucose cotransporter two inhibitors (SGLT2i). Methods: Using a 5% random sample of Medicare claims data, we identified 17,694 patients who filled ≥1 prescriptions for canagliflozin, dapagliflozin and empagliflozin in 2013-2016. The cohort was split randomly and equally into training and testing sets. We measured 65 predictor candidates using claims data from the year prior to SGLT2i initiation. We then applied three machine learning models, including random forests (RF), elastic net and least absolute shrinkage and selection operator (LASSO) for risk prediction. Results: The incidence rate of AKI was 1.1% over a median 1.5 year follow up. Among three machine learning methods, RF produced the best prediction (C-statistic = 0.72), followed by LASSO and elastic net (both C-statistics = 0.69). Among individuals classified in the top 10% of the RF risk score (i.e., high risk group), the actual incidence rate of AKI was as high as 3.7%. In the logistic regression model including 14 important risk factors selected by LASSO, use of loop diuretics [adjusted odds ratio (95% confidence interval): 3.72 (2.44-5.76)] had the strongest association with AKI incidence. Disscusion: Our machine learning model efficiently identified patients at risk of AKI among Medicare beneficiaries with T2D undergoing SGLT2i treatment.

Non-coding RNAs in Kawasaki disease: Molecular mechanisms and clinical implications.

Kawasaki disease (KD) is an acute self-limiting vasculitis with coronary complications, usually occurring in children. The incidence of KD in children is increasing year by year, mainly in East Asian countries, but relatively stably in Europe and America. Although studies on KD have been reported, the pathogenesis of KD is unknown. With the development of high-throughput sequencing technology, growing number of regulatory noncoding RNAs (ncRNAs) including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) have been identified to involved in KD. However, the role of ncRNAs in KD has not been comprehensively elucidated. Therefore, it is significative to study the regulatory role of ncRNA in KD, which might help to uncover new and effective therapeutic strategies for KD. In this review, we summarize recent studies on ncRNA in KD from the perspectives of immune disorders, inflammatory disorders, and endothelial dysfunction, and highlight the potential of ncRNAs as therapeutic targets for KD.