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Current Opinion in Critical Care Aug 2023Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse... (Review)
Review
PURPOSE OF REVIEW
Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse outcomes related to high Omega-6 content in soybean oil (SO) ILE's. This review summarizes recent literature on improved clinical outcomes with new Omega-6 lipid-sparing ILE's in PN management.
RECENT FINDINGS
Although there is a paucity of large-scale studies directly comparing Omega-6 lipid sparing ILE's with SO-based lipid emulsion use in PN in ICU patients, there is strong translational and meta-analysis evidence to suggest that lipid formulations containing fish oil (FO) and/or olive oil (OO) have favorable effects on immune function and improve clinical outcomes in ICU populations.
SUMMARY
More research is needed to directly compare omega-6-sparing PN formulas with FO and/or OO versus traditional SO ILE's. However, current evidence is promising for improved outcomes using newer ILE's including reduced infections, shorter lengths of stay, and reduced costs.
Topics: Humans; Fat Emulsions, Intravenous; Fish Oils; Olive Oil; Parenteral Nutrition; Soybean Oil
PubMed: 37306538
DOI: 10.1097/MCC.0000000000001058 -
Japanese Journal of Ophthalmology Sep 2023Having previously demonstrated the efficacy of 0.01% atropine eye drops for inhibiting progression of childhood myopia, we conducted additional analyses to assess... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Having previously demonstrated the efficacy of 0.01% atropine eye drops for inhibiting progression of childhood myopia, we conducted additional analyses to assess post-treatment changes in myopia progression.
STUDY DESIGN
Analysis of follow-up data from a previously reported randomized controlled trial METHODS: A mixed-effects model was used to compare intergroup changes in spherical equivalent (SE) and axial length (AL) at 1 month and 12 months after discontinuation of 2-year treatment with atropine or placebo in 167 school-age children.
RESULTS
Follow-up measurements were available for 149 participants at 1 month after discontinuation of treatment and for 51 participants at 12 months after discontinuation. At 1 month post-treatment, differences between the atropine and placebo groups in least squares (LS) mean changes in SE and AL, respectively, from 24 months were -0.06 diopters (D) (95% CI: -0.21, 0.08; P = .39) and 0.02 mm (95% CI: -0.05, 0.08; P = .60). At 12 months post-treatment, intergroup differences (atropine vs placebo) in LS mean changes in SE and AL, respectively, were -0.13 D (95% CI: -0.35, 0.10; P = .26) and -0.02 mm (95% CI: -0.12, 0.09; P = .75). LS mean changes in SE and AL from treatment discontinuation did not differ between the groups at 1 or 12 months post-treatment.
CONCLUSION
Axial elongation was significantly less in the atropine group than in the placebo group. The suppression effect obtained at 2 years was maintained after 12 months. The absence of intergroup differences in myopia progression since treatment cessation suggests that myopic rebound did not occur.
Topics: Humans; Child; Atropine; Ophthalmic Solutions; East Asian People; Disease Progression; Myopia; Refraction, Ocular; Axial Length, Eye
PubMed: 37548816
DOI: 10.1007/s10384-023-01012-8 -
Perfusion Nov 2023A basic prerequisite for a good surgical outcome in heart surgery is optimal myocardial protection. However, cardioplegia strategies used in adult cardiac surgery are...
INTRODUCTION
A basic prerequisite for a good surgical outcome in heart surgery is optimal myocardial protection. However, cardioplegia strategies used in adult cardiac surgery are not directly transferable to infant hearts. Paediatric microplegia, analogous to Calafiore cardioplegia used in adult cardiac surgery, offers the advantage of safe myocardial protection without haemodilution. The use of concentration-dependent paediatric microplegia is new in clinical implementation.
MATERIAL AND METHODS
Paediatric microplegia has been in clinical use in our institution since late 2014. It is applied via an 1/8 inch tube of a S5-HLM roller pump (LivaNova, Italy). As cardioplegic additive, a mixture of potassium (K) 20 mL (2 mmol/mL potassium chloride 14.9% Braun) and magnesium (Mg) 10 mL (4 mmol/mL Mg-sulphate Verla® i. v. 50%) is fixed into a syringe-pump (B. Braun, Germany). This additive is mixed with arterial patient blood from the oxygenator in different flowdependent ratios to form an effective cardioplegia.
TECHNIQUE
After microplegia application of initially 25 mmol/L K with 11 mmol/L Mg for 2 min, a safe cardioplegic cardiac arrest is achieved, which after release of the coronary circulation, immediately returns to a spontaneous cardiac-rhythm. In the case of prolonged aortic clamping, microplegia is repeated every 20 min with a reduction of the application dose of K by 20% and Mg by 30% (20 mmol/L K; 8.5 mmol/L Mg) and a further reduction down to a maintenance dose (15 mmol/L K; 6 mmol/L Mg) after additional 20 min.
SUMMARY
The microplegia adapted to the needs of paediatric myocardium is convincing due to its simple technical implementation for the perfusionist while avoiding haemodilution. However, the required intraoperative interval of microplegia of approx. 20 min demands adapted intraoperative management from the surgeon.
Topics: Adult; Humans; Child; Heart Arrest, Induced; Cardiac Surgical Procedures; Myocardium; Italy; Cardioplegic Solutions
PubMed: 36121780
DOI: 10.1177/02676591221127926 -
American Journal of Physiology. Cell... Dec 2023Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative...
Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K, low K, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K. Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by HO treatment. Our data support that high K concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage. Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.
Topics: Humans; Cardioplegic Solutions; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Myocytes, Cardiac; Potassium; Coronary Artery Disease; Antioxidants; Hydrogen Peroxide; Heart Arrest, Induced; Oxidative Stress; Reperfusion Injury; Aldehyde Reductase
PubMed: 37842750
DOI: 10.1152/ajpcell.00436.2022 -
Efficacy and safety of atropine in myopic children: A meta-analysis of randomized controlled trials.Journal Francais D'ophtalmologie Oct 2023To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for... (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the safety and efficacy of atropine for childhood myopia and further explore the optimal concentration of atropine, so as to provide more reference for clinical application.
METHODS
PubMed, Embase, Cochrane Library and ClinicalTrials.gov were comprehensively searched for randomized controlled trials (RCTs) up to October 14, 2021. The efficacy outcomes were progression of spherical equivalent (SE) and axial length (AL). The safety outcomes included accommodation amplitude, pupil size and adverse effects. The meta-analysis was performed using Review Manager 5.3.
RESULTS
Eighteen RCTs involving 3002 eyes were included. The results showed that at 6-36 months of treatment, atropine was effective in slowing the progression of myopia in children. At 12 months, the WMD of SE and AL of low-dose atropine was 0.25 diopters (D) and 0.1 millimeter (mm), moderate-dose atropine was 0.44 D and 0.16mm, high-dose atropine was 1.21 D and 0.82mm, respectively, compared with the control group. Similarly, at 24 months, low-dose atropine was 0.22 D and 0.14mm, moderate-dose atropine was 0.60 D, high-dose atropine was 0.66 D and 0.24mm, respectively. Interestingly, we also found that there was no significant difference in the effects of low-dose atropine on accommodation amplitude and photopic pupil size compared with the control group, and the rate of photophobia, allergy, blurred vision and other side effects was similar between the low-dose atropine group and the control group. In addition, atropine appears to be more effective in myopic children in China than in other countries.
CONCLUSIONS
Atropine in various concentrations can effectively slow myopia progression in children, and its effect is dose-dependent, while low-dose atropine (0.01% atropine) appears to be safer.
Topics: Child; Humans; Atropine; Ophthalmic Solutions; Randomized Controlled Trials as Topic; Myopia; Refraction, Ocular; Disease Progression
PubMed: 37147148
DOI: 10.1016/j.jfo.2023.01.030 -
Die Ophthalmologie Mar 2024In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and... (Review)
Review
BACKGROUND
In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief.
OBJECTIVE
Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given.
MATERIAL AND METHODS
Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented.
RESULTS
In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T‑helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC).
CONCLUSION
A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Tacrolimus; Immunologic Factors; Adjuvants, Immunologic; Ophthalmic Solutions
PubMed: 38363381
DOI: 10.1007/s00347-024-01996-9 -
Journal of the American Society of... Feb 2024This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance... (Observational Study)
Observational Study
SIGNIFICANCE STATEMENT
This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance hemodialysis patients. Using a large multinational cohort of 68,196 patients, we found that lower dialysate sodium concentrations (≤138 mmol/L) were independently associated with higher mortality compared with higher dialysate sodium concentrations (>138 mmol/L). The risk of death was lower among patients exposed to higher dialysate sodium concentrations, regardless of plasma sodium levels. These results challenge the prevailing assumption that lower dialysate sodium concentrations improve outcomes in hemodialysis patients. The study confirms that until robust evidence from randomized trials that are underway is available, nephrologists should remain cautious in reconsideration of dialysate sodium prescribing practices to optimize cardiovascular outcomes and reduce mortality in this population.
BACKGROUND
Excess mortality in hemodialysis (HD) patients is largely due to cardiovascular disease and is associated with abnormal fluid status and plasma sodium concentrations. Ultrafiltration facilitates the removal of fluid and sodium, whereas diffusive exchange of sodium plays a pivotal role in sodium removal and tonicity adjustment. Lower dialysate sodium may increase sodium removal at the expense of hypotonicity, reduced blood volume refilling, and intradialytic hypotension risk. Higher dialysate sodium preserves blood volume and hemodynamic stability but reduces sodium removal. In this retrospective cohort, we aimed to assess whether prescribing a dialysate sodium ≤138 mmol/L has an effect on survival outcomes compared with dialysate sodium >138 mmol/L after adjusting for plasma sodium concentration.
METHODS
The study population included incident HD patients from 875 Fresenius Medical Care Nephrocare clinics in 25 countries between 2010 and 2019. Baseline dialysate sodium (≤138 or >138 mmol/L) and plasma sodium (<135, 135-142, >142 mmol/L) concentrations defined exposure status. We used multivariable Cox regression model stratified by country to model the association between time-varying dialysate and plasma sodium exposure and all-cause mortality, adjusted for demographic and treatment variables, including bioimpedance measures of fluid status.
RESULTS
In 2,123,957 patient-months from 68,196 incident HD patients with on average three HD sessions per week dialysate sodium of 138 mmol/L was prescribed in 63.2%, 139 mmol/L in 15.8%, 140 mmol/L in 20.7%, and other concentrations in 0.4% of patients. Most clinical centers (78.6%) used a standardized concentration. During a median follow-up of 40 months, one third of patients ( n =21,644) died. Dialysate sodium ≤138 mmol/L was associated with higher mortality (multivariate hazard ratio for the total population (1.57, 95% confidence interval, 1.25 to 1.98), adjusted for plasma sodium concentrations and other confounding variables. Subgroup analysis did not show any evidence of effect modification by plasma sodium concentrations or other patient-specific variables.
CONCLUSIONS
These observational findings stress the need for randomized evidence to reliably define optimal standard dialysate sodium prescribing practices.
Topics: Humans; Dialysis Solutions; Retrospective Studies; Kidney Failure, Chronic; Renal Dialysis; Sodium
PubMed: 37967469
DOI: 10.1681/ASN.0000000000000262 -
Indian Journal of Ophthalmology May 2024
Topics: Humans; Drug Labeling; Presbyopia; Ophthalmic Solutions
PubMed: 38648444
DOI: 10.4103/IJO.IJO_1476_23 -
International Journal of Nanomedicine 2024Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including... (Review)
Review
Cataract is a leading cause of blindness globally, and its surgical treatment poses a significant burden on global healthcare. Pharmacologic therapies, including antioxidants and protein aggregation reversal agents, have attracted great attention in the treatment of cataracts in recent years. Due to the anatomical and physiological barriers of the eye, the effectiveness of traditional eye drops for delivering drugs topically to the lens is hindered. The advancements in nanomedicine present novel and promising strategies for addressing challenges in drug delivery to the lens, including the development of nanoparticle formulations that can improve drug penetration into the anterior segment and enable sustained release of medications. This review introduces various cutting-edge drug delivery systems for cataract treatment, highlighting their physicochemical properties and surface engineering for optimal design, thus providing impetus for further innovative research and potential clinical applications of anti-cataract drugs.
Topics: Humans; Cataract; Nanomedicine; Drug Delivery Systems; Nanoparticles; Animals; Lens, Crystalline; Cataract Extraction; Nanoparticle Drug Delivery System; Ophthalmic Solutions
PubMed: 38736657
DOI: 10.2147/IJN.S463679 -
Expert Opinion on Drug Delivery Mar 2024Research on nanotechnology in medicine has also involved the ocular field and nanomicelles are among the applications developed. This approach is used to increase both... (Review)
Review
INTRODUCTION
Research on nanotechnology in medicine has also involved the ocular field and nanomicelles are among the applications developed. This approach is used to increase both the water solubility of hydrophobic drugs and their penetration/permeation within/through the ocular tissues since nanomicelles are able to encapsulate insoluble drug into their core and their small size allows them to penetrate and/or diffuse through the aqueous pores of ocular tissues.
AREAS COVERED
The present review reports the most significant and recent literature on the use of nanomicelles, made up of both surfactants and amphiphilic polymers, to overcome limitations imposed by the physiology of the eye in achieving a high bioavailability of drugs intended for the therapeutic areas of greatest commercial interest: dry eye, inflammation, and glaucoma.
EXPERT OPINION
The results of the numerous studies in this field are encouraging and demonstrate that nanomicelles may be the answer to some of the challenges of ocular therapy. In the future, new molecules self-assembling into micelles will be able to meet the regulatory requirements for marketing authorization for their use in ophthalmic formulations.
Topics: Micelles; Humans; Ophthalmic Solutions; Animals; Nanoparticles; Administration, Ophthalmic; Drug Delivery Systems; Surface-Active Agents; Biological Availability; Solubility; Nanotechnology; Polymers; Glaucoma
PubMed: 38396342
DOI: 10.1080/17425247.2024.2323208