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This article discusses the use of an axillary implanted micro-axial blood pump to facilitate off-pump coronary artery bypass grafting (OPCAB) in patients with severely reduced left ventricular function. The study involved nine male patients with multivessel coronary artery disease and a mean age of 67.8 years. The implantation of the axillary pump was successful in all patients, and complete revascularization was achieved. The patients experienced a low rate of complications, and hospital and mid-term survival rates were 100%. The study concludes that protected OPCAB using an axillary implanted micro-axial ventricular assist device is feasible and safe for patients with severely reduced left ventricular function. [Extracted from the article]

This article, titled "Coronary Artery Bypass Grafting in the Elderly: Analysis of a 12 Year-Experience in a Single Center," examines the surgical treatment of coronary heart disease in patients over the age of 75. The study analyzes data from 4,931 coronary artery bypass grafting (CABG) procedures performed between 2010 and 2021. The results show that elderly patients had a higher prevalence of female gender and left main stenoses. They also had a higher incidence of central neurological disease and extracardiac arteriopathy. The study suggests that a less complex surgical approach and the use of hybrid revascularization techniques may result in shorter operation times and lower postoperative cardiovascular morbidity in elderly patients. However, older patients had an increased risk of postoperative renal failure and 30-day mortality due to more comorbidities. [Extracted from the article]

Background: Dry eye disease (DED) is commonly caused by excessive tear film evaporation due to Meibomian gland dysfunction (MGD). There is a need for DED treatment options that address tear evaporation and benefit patients across a broad range of demographic and disease characteristics. This study evaluated treatment effects of perfluorohexyloctane ophthalmic drop (formerly NOV03) in the pooled dataset from 2 pivotal clinical trials in patients with DED associated with MGD, both in the overall population and in patient subgroups based on sex, age, and baseline severity of eye dryness., Methods: Pooled data from 2 similarly designed, phase 3, randomized controlled trials (GOBI, MOJAVE) were analyzed. Patients aged ≥18 years with DED administered perfluorohexyloctane (n=614) or hypotonic (0.6% solution) saline control (n=603) four times daily for 8 weeks. Primary endpoints were total corneal fluorescein staining (tCFS) score (National Eye Institute scale, 0-15) and eye dryness visual analog scale (VAS) score (0-100). Efficacy was evaluated using analysis of covariance among patient subgroups (male and female, older [≥65 years] and younger [18 to <65 years], tCFS score <7 and ≥7, VAS eye dryness score <70 and ≥70, MGD score <7 and ≥7, Schirmer I test <10 mm and ≥10 mm)., Results: Reductions in tCFS and VAS eye dryness scores were greater for perfluorohexyloctane versus control. In the overall patient population, least-squares mean treatment difference was -1.1 (95% CI: -1.41 to -0.79; p<0.0001) for tCFS and -9.0 (95% CI: -11.90 to -6.00; p<0.0001) for VAS eye dryness. Treatment favored perfluorohexyloctane over control in all patient subgroup analyses of tCFS and VAS eye dryness. Overall, the most common adverse event with perfluorohexyloctane was blurred vision (2.1% of patients), which was mild and transient., Conclusions: Compared with a hypotonic saline control, perfluorohexyloctane improved both the signs and symptoms of DED, including in patients with greater self-reported severity of eye dryness., Clinical Trial Registration: This study represents an integrated analysis of 2 previous clinical trials: GOBI (ClinicalTrials.gov, NCT04139798) and MOJAVE (ClinicalTrials.gov, NCT04567329)., Competing Interests: AF was employed by company Minnesota Eye Consultants. DE was employed by company Total Eye Care. JT was employed by company Tauber Eye Center. JS was employed by company Virginia Eye Consultants. AF reports serving on advisory boards, speakers bureaus, or as a consultant for Allergan, BioTissue, Dompé, Lumenis Be, NovaBay, Oyster Point Pharma, and Sight Sciences. JH reports serving on advisory boards or as an investigator for Bausch + Lomb, Novartis, Johnson & Johnson, Kala Pharmaceuticals, and Ocular Therapeutix. DE reports serving on advisory board for Visus Therapeutics and reports presently serving as an investigator for Alcon Research, Bausch + Lomb, Glaukos, Johnson & Johnson Vision, Kowa, Mimetogen Pharmaceuticals, Novartis, Ocular Therapeutix, Oculis, Stuart Therapeutics, and Visus Therapeutics. JG reports presently serving as an investigator for Allergan, Bausch + Lomb, Calm Water Therapeutics, LENZ Therapeutics, Mimetogen Pharmaceuticals, and Sylentis. JT reports serving as an investigator for Alcon, Aramis Biosciences, Bausch + Lomb, Claris Bio, Novaliq, Novartis, Oyster Point Pharma, Sylentis, Tarsus, TearSolutions, Trefoil Therapeutics, and Visus Therapeutics. JS reports serving on advisory boards, speakers bureaus, or as a consultant for 1-800-DOCTORS, AbbVie, Aerie, Alcon, Aldeyra Therapeutics, Allergan, ArcScan, Avedro, Bausch + Lomb, Bio-Tissue/TissueTech, BioLayer, Bruder Healthcare, Claris Bio, Clearside Biomedical, Clearview, Clementia Pharmaceuticals, Dompé, Eleven Optical, Eyedetec Medical, EyeGate, Eyevance Pharmaceuticals, Fortress Biotech, Glaukos, Hovione, Imprimis Pharmaceuticals, Inspire Pharmaceuticals/Merck & Co, Inc, Isis (Ionis) Pharmaceuticals, Johnson & Johnson/TearScience/Vistakon, Kala Pharmaceuticals, Kowa Pharmaceuticals America, LacriSciences Vision, LayerBio, Lenstatin, Lumenis Be, Lux Biosciences, Mallinckrodt, Mati Therapeutics, MedEdicus, Mitotech, SA, Nicox, NovaBay Pharmaceuticals, Novaliq GmbH, Novartis Pharmaceuticals, Noveome Biotherapeutics/Stemnion, OcuCure Therapeutics, Ocular Therapeutix, Oculis, Okogen, Omeros, Oyster Point Pharma, Parion Sciences, PentaVision, Pfizer, Portage, Quidel, Rapid Pathogen Screening, Santen Pharmaceutical, ScienceBased Health, Shire, Sun Pharmaceutical Industries, Surrozen, Synergel, Takeda Pharmaceutical, Talia Technology, TearLab, TearSolutions, Topcon Healthcare, and TopiVert Pharma; conducting clinical research for AbbVie, Alcon, Aldeyra Therapeutics, Allergan, ArcScan, Avedro, Bausch + Lomb, Clearside Biomedical, Clearview, Clementia Pharmaceuticals, Dompé, EyeGate Research, EyeRx Research, Fortress Biotech, Glaukos, Hovione, InSite Vision, Inspire Pharmaceuticals/Merck & Co, Inc, Ionis Pharmaceuticals, Johnson & Johnson/TearScience/Vistakon, Kala Pharmaceuticals, LacriSciences Vision, Lux Biosciences, Mimetogen Pharmaceuticals, Mitotech, SA, NeoMedix Corporation, Novaliq GmbH, Novartis Pharmaceuticals, Ocular Therapeutix, Okogen, Oyster Point Pharma, Parion Sciences, Pfizer, Rapid Pathogen Screening, Rutech, Santen Pharmaceutical, Senju Pharmaceutical, Shire, TearSolutions, Topcon Healthcare, and XOMA/Servier; investor, shareholder, or stock interests in 1-800-DOCTORS, Alphaeon (parent company: Strathspey Crown), BioLayer, Eyedetec Medical, EyeGate Research, EyeRx Research, Eyevance Pharmaceuticals, LacriSciences Vision, LayerBio, Mati Therapeutics, NovaBay Pharmaceuticals, Noveome Biotherapeutics/Stemnion, OccuHub, OcuCure Therapeutics, Okogen, Oyster Point Pharma, Rapid Pathogen Screening, Shire, and TearLab. SK is an employee of Novaliq GmbH. JV is an employee of Bausch + Lomb., (Copyright © 2024 Fahmy, Harthan, Evans, Greiner, Tauber, Sheppard, Krösser and Vittitow.)

Background: Deep brain stimulation of the central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT)., Objectives: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice., Methods: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording electroencephalogram (EEG). We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration., Results: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, including currents as low as 20 μA., Conclusion: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings., Competing Interests: Declaration of competing interest Emery N. Brown holds patents on anesthetic state monitoring and control; holds founding interest in PASCALL, a start-up developing physiological monitoring systems; receives royalties from intellectual property through Massachusetts General Hospital licensed to Masimo. The interests of Emery N. Brown were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. The rest of the authors do not have any interest to report., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We asked whether acute redox signaling from mitochondria exists concomitantly to fatty acid- (FA-) stimulated insulin secretion (FASIS) at low glucose by pancreatic β-cells. We show that FA β-oxidation produces superoxide/H 2 O 2 , providing: i) mitochondria-to-plasma-membrane redox signaling, closing K ATP -channels synergically with elevated ATP (substituting NADPH-oxidase-4-mediated H 2 O 2 -signaling upon glucose-stimulated insulin secretion); ii) activation of redox-sensitive phospholipase iPLA 2 γ/PNPLA8, cleaving mitochondrial FAs, enabling metabotropic GPR40 receptors to amplify insulin secretion (IS). At fasting glucose, palmitic acid stimulated IS in wt mice; palmitic, stearic, lauric, oleic, linoleic, and hexanoic acids also in perifused pancreatic islets (PIs), with suppressed 1st phases in iPLA 2 γ/PNPLA8-knockout mice/PIs. Extracellular/cytosolic H 2 O 2 -monitoring indicated knockout-independent redox signals, blocked by mitochondrial antioxidant SkQ1, etomoxir, CPT1 silencing, and catalase overexpression, all inhibiting FASIS, keeping ATP-sensitive K + -channels open, and diminishing cytosolic [Ca 2+ ]-oscillations. FASIS in mice was a postprandially delayed physiological event. Redox signals of FA β-oxidation are thus documented, reaching the plasma membrane, essentially co-stimulating IS., Competing Interests: Declaration of competing interest There are no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Mitochondria (mt) represent the vital hub of the molecular physiology of the cell, being decision-makers in cell life/death and information signaling, including major redox regulations and redox signaling. Now we review recent advances in understanding mitochondrial redox homeostasis, including superoxide sources and H2O2 consumers, i.e., antioxidant mechanisms, as well as exemplar situations of physiological redox signaling, including the intramitochondrial one and mt-to-cytosol redox signals, which may be classified as acute and long-term signals. This review exemplifies the acute redox signals in hypoxic cell adaptation and upon insulin secretion in pancreatic beta-cells. We also show how metabolic changes under these circumstances are linked to mitochondrial cristae narrowing at higher intensity of ATP synthesis. Also, we will discuss major redox buffers, namely the peroxiredoxin system, which may also promote redox signaling. We will point out that pathological thresholds exist, specific for each cell type, above which the superoxide sources exceed regular antioxidant capacity and the concomitant harmful processes of oxidative stress subsequently initiate etiology of numerous diseases. The redox signaling may be impaired when sunk in such excessive pro-oxidative state.

Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability-the ability of the brain to balance excitability with the need to be stable and controllable. To test this hypothesis, we developed a method for quantifying changes in population-level dynamic stability in complex systems: delayed linear analysis for stability estimation (DeLASE). Propofol was used to transition animals between the awake state and anesthetized unconsciousness. DeLASE was applied to macaque cortex local field potentials (LFPs). We found that neural dynamics were more unstable in unconsciousness compared with the awake state. Cortical trajectories mirrored predictions from destabilized linear systems. We mimicked the effect of propofol in simulated neural networks by increasing inhibitory tone. This in turn destabilized the networks, as observed in the neural data. Our results suggest that anesthesia disrupts dynamical stability that is required for consciousness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this report is to describe atypical corneal complications associated with dupilumab use., Methods: This is a series of four cases of adult patients with infiltrative or ulcerative keratitis secondary to dupilumab use., Results: All four patients in this series were prescribed dupilumab for the treatment of atopic dermatitis and developed infiltrative or ulcerative corneal lesions. In all cases, corneal disease was successfully managed with immediate discontinuation of dupilumab and topical steroid treatment. In two cases, the patient also received antibiotic eye drops for infection precautions., Conclusions: Although dupilumab is most commonly associated with conjunctivitis, physicians should be aware of potential severe corneal complications for early identification and intervention., Competing Interests: J. J. Kang: Sanofi (C); All other authors: No conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Introduction: The study aimed to evaluate multi-symptom relief of dry eye manifestations with the use of propylene glycol-hydroxypropyl-guar (PG-HPG) nanoemulsion lubricant eye drops, among subjects with dry eye disease (DED)., Methods: This was a post-marketing, prospective, single-arm study conducted in the USA. Subjects aged ≥ 18 years, with tear breakup time (TBUT) ≤ 10 s for both eyes, dry eye questionnaire-5 (DEQ-5) "watery eyes" symptom score 1-4, symptoms of burning/stinging, sore and tired eyes as determined by impact of dry eye on everyday living-symptom bother (IDEEL-SB) questionnaire, and IDEEL-SB score 16-65 were included. Subjects were required to complete IDEEL-SB and DEQ-5 at days 0, 14 ± 2, and 28 ± 2, and self-administer one drop of PG-HPG four times daily for 28 ± 2 days. Primary endpoints were change from baseline at day 28 in symptoms of sore, stinging/burning, and tired eyes on IDEEL-SB; and symptom of watery eyes on DEQ-5. Other endpoints evaluated were corneal staining and TBUT at baseline and day 28 ± 2; symptom relief (5-point Likert scale) at day 28 ± 2, and safety., Results: Of 119 subjects enrolled, 95 completed the study (mean ± SD age 61.2 ± 13.0 years; female 69.5%). Mean IDEEL-SB scores reduced significantly from baseline at day 28 for symptoms of aching/sore eyes (change from baseline - 1.0 ± 1.1), burning/stinging eyes (change from baseline - 1.1 ± 0.9), and tired eyes (change from baseline - 1.1 ± 1.0) (all p < 0.0001). Mean DEQ-5 score for watery eye symptoms significantly reduced from baseline at day 28 (change from baseline - 0.9 ± 1.0, p < 0.0001). Corneal staining at day 28 was comparable to baseline. TBUT improved from baseline to day 28. On a Likert scale, more than 50% of subjects reported relief from symptoms of sore, stinging, and burning eyes. Three (3.1%) subjects reported treatment-emergent adverse events (non-ocular)., Conclusions: PG-HPG nanoemulsion lubricant eye drops significantly improved multiple dry eye symptoms in subjects with DED over 28 days, with no new safety concerns., Trial Registration: ClinicalTrials.gov Identifier, NCT05056155., (© 2023. The Author(s).)

Objective: Patients who are intubated and sedated are at risk for developing exposure keratopathy, which can lead to permanent vision loss. This retrospective study assesses the incidence of exposure keratopathy (EK) in intensive care unit (ICU) patients before and after implementation of an EK Prevention Order Set., Methods: At one tertiary care hospital (Bronx, NY), an "Exposure Keratopathy Prevention Order Set" was implemented to ameliorate this risk which included the application of white petrolatum-mineral oil lubricating ointment every 6 hours in both eyes. This retrospective chart review study analyzed the incidence of EK diagnosis before and after implementation of this EK Prevention Order Set. Patients who were on mechanical ventilation at the time of ophthalmology consult request between January 1, 2021, and December 31, 2021, were included. Ophthalmology consult notes of patients with EK diagnosis were reviewed for details regarding the consult request, examination findings, diagnosis, and treatment plan., Results: There were 247 and 361 ventilated ICU patients before and after the order set, respectively. The number of ophthalmology consults decreased slightly after the order set from 15 of 247 to 20 of 361 ventilated patients. In addition, the rate of EK among ventilated patients decreased from 4.5% (11 of 247 patients over 151 days) to 2.2% (8 of 361 patients over 212 days; P =0.154) with a risk ratio of 0.50 (95% CI 0.20-1.22)., Conclusion: The number of patients diagnosed with EK trended down after implementation of the EK Prevention Order Set., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Contact Lens Association of Ophthalmologists.)

Objective: By exposing mice carrying a deletion of NADPH oxidase isoform 4, NOX4, specifically in pancreatic β cells (βNOX4-/-) to nutrient excess stimulated by a high-fat diet (HFD), this study aimed to elucidate the role of β-cell redox status in the development of meta-inflammation within the diabetic phenotype., Methods: The authors performed basic phenotyping of βNOX4-/- mice on HFD involving insulin and glycemic analyses, histochemistry of adipocytes, indirect calorimetry, and cytokine analyses. To characterize local inflammation, the study used caspase-1 activity assay, interleukin-1β immunochemistry, and real-time polymerase chain reaction during coculturing of β cells with macrophages., Results: The phenotype of βNOX4-/- mice on HFD was not associated with hyperinsulinemia and hyperglycemia but showed accumulation of excessive lipids in epididymal fat and β cells. Surprisingly, mice showed significantly reduced systemic inflammation. Decreased interleukin-1β protein levels and downregulated NLRP3-inflammasome activity were observed on chronic glucose overload in βNOX4-/- isolated islets and NOX4-silenced INS1-E cells resulting in attenuated proinflammatory polarization of macrophages/monocytes in vitro and in situ and reduced local islet inflammation., Conclusions: Experimental evidence suggests that NOX4 pro-oxidant activity in β cells is involved in NLRP3-inflammasome activation during chronic nutrient overload and participates in local inflammatory signaling and perhaps toward peripheral tissues, contributing to a diabetic inflammatory phenotype., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)