Blood Oxygen Research Articles

Theoretical Evaluation of Simultaneous Optical Measurement Method for Hemoglobin Concentration, Oxygen Saturation, and Water Percentage in Blood Based on Multi-parameter Optimization

Theoretical Evaluation of Simultaneous Optical Measurement Method for Hemoglobin Concentration, Oxygen Saturation, and Water Percentage in Blood Based on Multi-parameter Optimization

Diabetes drugs activate neuroprotective pathways in models of neonatal hypoxic-ischemic encephalopathy.

Hypoxic-ischaemic encephalopathy (HIE) arises from diminished blood flow and oxygen to the neonatal brain during labor, leading to infant mortality or severe brain damage, with a global incidence of 1.5 per 1000 live births. Glucagon-like Peptide 1 Receptor (GLP1-R) agonists, used in type 2 diabetes treatment, exhibit neuroprotective effects in various brain injury models, including HIE. In this study, we observed enhanced neurological outcomes in post-natal day 10 mice with surgically induced hypoxic-ischaemic (HI) brain injury after immediate systemic administration of exendin-4 or semaglutide. Short- and long-term assessments revealed improved neuropathology, survival rates, and locomotor function. We explored the mechanisms by which GLP1-R agonists trigger neuroprotection and reduce inflammation following oxygen-glucose deprivation and HI in neonatal mice, highlighting the upregulation of the PI3/AKT signalling pathway and increased cAMP levels. These findings shed light on the neuroprotective and anti-inflammatory effects of GLP1-R agonists in HIE, potentially extending to other neurological conditions, supporting their potential clinical use in treating infants with HIE.

An Analysis of the Physiological and Psychological Responses Elicited When Wearing an Aerogel Cold Protective Jacket in Airflow

This study evaluated the thermal physiological and psychological responses elicited when wearing cold protective jackets with aerogel fillings in two cold environments, one without air velocities and one with air velocities (2.3 m·s-1), at an air temperature of 10°C. The participants were five healthy young males. Measures were taken of physiological parameters, blood pressure (BP), heart rate (HR), core temperature, oxygen uptake (Vo2), and microclimate (temperature and humidity). The psychological parameters evaluated were thermal and wetness sensation. No differences were observed in systolic blood pressure, heart rate, and oxygen intake between the conditions. At tympanic temperature, a significant difference was observed between the conditions during exercise (p <.05); . A significant difference was observed in the microclimate temperature of the clothing according to the airflow, and temperature changes in the chest and back revealed different patterns. Significant differences were observed in thermal sensation (whole body (p <.05), chest (p <.05), back (p <.01)) between airflow conditions. The results therefore indicate that cold protective jackets with an aerogel filling are suitable for people operating in low-temperature and airflow environments.

#686 The impact of Ferric Derisomaltose (FDI) on role physical functioning in iron deficient but not anaemic patients with chronic kidney disease

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive disorder affecting physiological function, specifically iron deficiency. Iron is crucial for red blood cell production, oxygen transport, mitochondrial function, and cardiac function. Iron deficiency in patients with CKD results from decreased absorption and mobilization, which leads to anaemia, reduced functional capacity, increased cardiac risk, and poorer quality of life. The Iron and the Heart Trial investigated whether correcting iron deficiency in CKD patients (using a single dose of 1000 mg of intravenous (IV) ferric derisomaltose (FDI)) improved functional capacity, as measured by the six-minute walk test, and health-related quality of life (HRQoL) outcomes, including Physical and Mental Health. The SF-36v2 Health Survey tool was used to quantify HRQoL outcomes. Patients identify that whilst clinical outcomes such as survival and functional capacity are important; HRQoL and the symptoms associated with disease burden are far more debilitating. Currently research on how Role Physical functioning, which assesses limitations in routine activities, affects QoL in people with CKD and iron deficiency is limited. This study aimed to explore if correcting iron deficiency in people with CKD without anaemia using IV FDI, improved Role Physical outcomes compared to a placebo group post-infusion at 3 months from the Iron and Heart Trial. Method The Iron and the Heart Trial was a multicentre double blinded randomised study in which non-anaemic CKD patients with iron deficiency were given 1000 mg of IV iron (FDI), compared to a placebo infusion at baseline, and assessed at 1 month and 3-months post-infusion, to evaluate the impact on exercise capacity. Secondary objectives of the trial included impact of iron therapy on QoL. This analysis focused on “Role Physical” as a QoL parameter in the trial participants. A total of 54 CKD patients with iron deficiency but no anaemia (Group 1) were enrolled in the trial and randomly assigned in a 1:1 ratio to either the FDI or placebo group. Within the 54 patients, 26 patients received FDI, and 28 patients received placebo. 10 CKD patients without anaemia or iron deficiency (Group 2) were also included, they did not receive any treatment and were followed up at the same time points as Group 1. Each group completed the Role Physical parameter of the SF-36v2 survey which assessed if participants had cut down the amount of time spent on activities, accomplished less, were limited, or performed tasks with more difficulty because of their condition. The collected responses were categorical variables that were summarised using number (%) and then normalised and summarised using mean (standard deviations). All analyses were undertaken using Microsoft Excel. Results At baseline the Role Physical means (SD) were as follows: placebo 42.8 ± 11.9, FDI 42.1 ± 11.0, Group 2 45.9 ± 9.4. Prior to any intervention, mean Role Physical outcomes were numerically poorer in those with CKD and iron deficiency (placebo and FDI) compared to those with CKD and no iron deficiency (Group 2) (Fig. 1a). Following intervention at 3 months the mean (SD) scores for each group were—placebo 37.5 ± 14.6, FDI 40.9 ± 11.4, Group 2 44.0 ± 13.2. The placebo group experienced a decrease of 12.3% in the mean score for Role Physical outcomes in comparison to their baseline whilst, FDI group only experienced a 3% decrease. For Group 2, there was a decrease of 4% from baseline to 3 months (Fig. 1b). Conclusion Our study showed that while FDI may not improve QoL outcomes, Role Physical functioning, in individuals with CKD and iron deficiency, it may still play a role in slowing the deterioration of these outcomes. Caution must be exercised when interpreting our findings due to the limitations of our study, and further research with sufficient power is needed to extend the findings of the study with a larger sample size to be able to make treatment recommendations for individuals with CKD and iron deficiency.

Cardiovascular and cerebrovascular effects of caffeine maintenance in preterm infants during the transitional period.

Caffeine is routinely used for the prophylaxis of prematurity-related apnoeas. We aimed to evaluate the effect of caffeine maintenance on cardiovascular and cerebrovascular haemodynamics using a non-invasive multimodal monitoring in preterm infants during the transitional period. Infants <32 weeks' gestational age (GA) were enrolled in this observational prospective study. The following parameters were recorded before and after the administration of caffeine citrate 5 mg/kg using near-infrared spectroscopy, pulse oximetry and electrical velocimetry: heart rate, cardiac output, stroke volume, cardiac contractility, systemic vascular resistance (SVR), perfusion index, peripheral and cerebral oxygenation, cerebral fractional oxygen extraction, correlation index between cerebral oxygenation and heart rate (TOHRx, marker of cerebrovascular reactivity). Multilevel mixed-effects linear models were used to assess the impact of caffeine and of relevant clinical covariates on each parameter. Seventy-seven infants (mean GA 29.3 ± 2.5 weeks, mean birthweight 1148 ± 353 g) were included. Caffeine administration was associated with increased SVR (B = 0.623, p = 0.004) and more negative TOHRx values (B = -0.036, p = 0.022), which suggest improved cerebrovascular reactivity. Caffeine administration at maintenance dosage during postnatal transition is associated with increased systemic vascular tone and improved cerebrovascular reactivity. A possible role for caffeine-mediated inhibition of adenosine receptors may be hypothesized. This study provides a thorough and comprehensive overview of multiple cerebrovascular and cardiovascular parameters, monitored non-invasively by combining near-infrared spectroscopy, electrical velocimetry and pulse oximetry, before and after the administration of caffeine at maintenance dosage in preterm infants during postnatal transition. Caffeine was associated with an improvement in cerebrovascular reactivity and with a slight but significant increase in systemic vascular resistance, with no additional effects on other cardiovascular and cerebrovascular parameters. Our results support the safety of caffeine treatment even during a phase at risk for haemodynamic instability such as postnatal transition and suggest potential beneficial effects on cerebral haemodynamics.

Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings

IntroductionHigh sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). MethodsWe performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. ResultsLiking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. ConclusionWe found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.

Quantitative evaluation of the impact of variation of optical parameters on the estimation of blood hematocrit and oxygen saturation for dual-wavelength photoacoustics

Photoacoustic (PA) spectroscopy is considered to be one of the most effective ways to measure the levels of hematocrit (H) and oxygenation saturation (SO2) of blood, which are essential for diagnosing blood-related illnesses. This simulation study aims to investigate the impact of individual optical parameters, i.e., optical absorption coefficient (μ a ), scattering coefficient (μ s ), and anisotropy factor (g), on the accuracy of this technique in estimating the blood properties. We first performed the Monte Carlo simulations, using realistic optical parameters, to obtain the fluence maps for various samples. The wavelengths of the incident light were chosen to be 532, 700, 1000, and 1064 nm. Thereafter, the k-Wave simulations were executed, incorporating those fluence maps to generate the PA signals. The blood properties were obtained using the PA signals. We introduced variations in μ a , μ s , and g ranging from −10% to +10%, −10% to +10%, and −5% to +1%, respectively, at 700 and 1000 nm wavelengths. One parameter, at both wavelengths, was changed at a time, keeping others fixed. Subsequently, we examined how accurately the blood parameters could be determined at physiological hematocrit levels. A 10% variation in μ a induces a 10% change in H estimation but no change in SO2 determination. Almost no change has been seen for μ s variation. However, a 5% (−5% to 0%) variation in the g factor resulted in approximately 160% and 115% changes in the PA signal amplitudes at 700 and 1000 nm, respectively, leading to ≈125% error in hematocrit estimation and ≈14% deviation in SO2 assessment when nominal SO2=70%. It is clear from this study that the scattering anisotropy factor is a very sensitive parameter and a small change in its value can result in large errors in the PA estimation of blood properties. In the future, in vitro experiments with pathological blood (inducing variation in the g parameter) will be performed, and accordingly, the accuracy of the PA technique in quantifying blood H and SO2 will be evaluated.

Does Time to Asystole in Donors After Circulatory Death Impact Recipient Outcome in Liver Transplantation?

The agonal phase can vary following treatment withdrawal in donor after circulatory death (DCD). There is little evidence to support when procurement teams should stand down in relation to donor time to death (TTD). We assessed what impact TTD had on outcomes following DCD liver transplantation. Data were extracted from the UK Transplant Registry on DCD liver transplant recipients from 2006 to 2021. TTD was the time from withdrawal of life-sustaining treatment to asystole, and functional warm ischemia time was the time from donor systolic blood pressure and/or oxygen saturation falling below 50 mm Hg and 70%, respectively, to aortic perfusion. The primary endpoint was 1-y graft survival. Potential predictors were fitted into Cox proportional hazards models. Adjusted restricted cubic spline models were generated to further delineate the relationship between TTD and outcome. One thousand five hundred fifty-eight recipients of a DCD liver graft were included. Median TTD in the entire cohort was 13 min (interquartile range, 9-17 min). Restricted cubic splines revealed that the risk of graft loss was significantly greater when TTD ≤14 min. After 14 min, there was no impact on graft loss. Prolonged hepatectomy time was significantly associated with graft loss (hazard ratio, 1.87; 95% confidence interval, 1.23-2.83; P = 0.003); however, functional warm ischemia time had no impact (hazard ratio, 1.00; 95% confidence interval, 0.44-2.27; P > 0.9). A very short TTD was associated with increased risk of graft loss, possibly because of such donors being more unstable and/or experiencing brain stem death as well as circulatory death. Expanding the stand down times may increase the utilization of donor livers without significantly impairing graft outcome.

Thermal and functional condition of microbiological laboratory workers when using personal protective equipment against biological factors

Introduction. The use of personal protective equipment (PPE) against pathogenic biological agents (PBA) by medical workers in microbiological laboratories is a mandatory requirement for infectious safety, however, low or absent air and vapor permeability of these PPE and their elements can contribute to disruption of the functional and thermal state. The aim of the study is a physiological and hygienic assessment of PPE against pathogenic pathogens based on indicators of the thermal state of the body when modeling the professional activities of microbiological laboratory workers. Materials and methods. The study was conducted on the basis of the laboratory of personal protective equipment and industrial exoskeletons of Izmerov Research Institute of Occupational Health on 12 practically healthy individuals — male and female medical workers while simulating work activities and sanitary and epidemiological requirements for a microbiological laboratory. Results. The values of skin and body temperature, heart rate, blood pressure and blood oxygen saturation levels obtained in the dynamics of the study made it possible to determine the degree of stress in the thermal and functional state of the body of medical workers. The indicators obtained during the experiment were assessed in accordance with current regulatory documents. A number of thermal state indicators obtained during the study had statistically significant differences from their initial values at p&lt;0.05. Conclusions. When using personal protective equipment against pathogenic pathogens under comfortable microclimatic conditions, an increase in some criterion indicators of the examined individuals was noted, in particular to the upper limit of permissible values of thermal state, which indicates the leading influence of PPE on the thermoregulation of the body and necessitates a reduction in the process of production activities and requires limiting the maximum duration of a work shift under given conditions is three hours, followed by a break to restore the thermal state and water-salt balance. Ethics. The study was conducted in compliance with ethical principles and norms, an extract from the minutes of the meeting of the local ethics committee No. 9 dated 11/23/2022 was obtained.

Review on Pregnancy Progress Monitoring

This project outlines the creation of an innovative pregnancy progress monitoring system leveraging cutting-edge sensor technology and artificial intelligence (AI) models. This project presents an integrated system designed to revolutionize the monitoring of pregnancy progression through a sophisticated fusion of sensor technology and artificial intelligence (AI). The collaborative functionality of DS18B20 temperature sensors, heart beat sensor, and GSM modules establishes a seamless data collection and transmission framework. These sensors continuously capture vital parameters including body temperature, heart rate, and blood oxygen saturation, while the GSM module ensures secure and real-time transmission of this data to designated servers or caregivers’ devices. Leveraging AI-driven algorithms, the system interprets these multifaceted datasets, employing pattern recognition and anomaly detection to discern potential health irregularities. The intuitive user interface grants caregivers comprehensive access to visualized data, facilitating proactive monitoring and swift response through customizable alerts for critical health indicators. This innovative solution undergoes iterative development and validation, seeking to redefine prenatal care by enabling early identification of deviations and fostering informed decision-making among medical practitioners and expectant parents. By amalgamating sensor technology with AI capabilities, this system aspires to enhance the safety and well-being of both mother and fetus, marking a paradigm shift in prenatal health monitoring and intervention strategies.

Photoacoustic/ultrasound dual-modal imaging of human nails: A pilot study

Traditional diagnostic techniques including visual examination, ultrasound (US), and magnetic resonance imaging (MRI) have limitations of in-depth information for the detection of nail disorders, resolution, and practicality. This pilot study, for the first time, evaluates a dual-modality imaging system that combines photoacoustic tomography (PAT) with the US for the multiparametric quantitative assessment of human nail. The study involved a small cohort of five healthy volunteers who underwent PAT/US imaging for acquiring the nail unit data. The PAT/US dual-modality imaging successfully revealed the fine anatomical structures and microvascular distribution within the nail and nail bed. Moreover, this system utilized multispectral PAT to analyze functional tissue parameters, including oxygenated hemoglobin, deoxyhemoglobin, oxygen saturation, and collagen under tourniquet and cold stimulus tests to evaluate changes in the microcirculation of the nail bed. The quantitative analysis of multispectral PAT reconstructed images demonstrated heightened sensitivity in detecting alterations in blood oxygenation levels and collagen content within the nail bed, under simulated different physiological conditions. This pilot study highlights the potential of PAT/US dual-modality imaging as a real-time, noninvasive diagnostic modality for evaluating human nail health and for early detection of nail bed pathologies.

Assessment of choroidal perfusion indices in thyroid eye disease by using optical coherence tomography.

To study choroidal vascularity changes in active and inactive TED orbits by using high-definition optical coherence tomography (HD-OCT) and correlate the changes with the duration and severity of TED and Barrets' index. A cross-sectional study wherein 37 TED orbits and 30 healthy control (HC) orbits were enrolled. Choroid was imaged using HD-OCT scans centered at the fovea, and subfoveal choroidal thickness (SFCT) was measured. The OCT images were analyzed using ImageJ software to calculate choroidal vascularity index (CVI) and associated choroidal perfusion indices. The study included eight active, 13 non-inflammatory active (NIA), and 16 inactive TED orbits. The mean age was 39.73 ± 12.91 years, and the male: female ratio was 1.18:1. Intraocular pressure and CVI were higher, while SFCT was similar in TED on comparison to healthy orbits. CVI and SFCT were raised in active as compared to inactive TED. CVI and SFCT correlated positively with Barrets' index and negatively with the duration of thyroid disease. The area under curve of CVI (95% CI: 0.651-0.864, P < 0.001) helped in differentiating TED orbits from HC, while CVI (95% CI: 0.780-0.983, P < 0.001) had the maximum discriminatory power in predicting the activity of disease. CVI has greater sensitivity than SFCT in differentiating healthy from TED orbits. The blood flow stagnation in active orbits, which improves during the course of TED and tends to worsen with increase in Barret's index, can lead to choroidal vascularity changes. CVI and SFCT can act as adjunct to existing modalities for monitoring the disease activity.

The Development and Implementation of Innovative Blind Source Separation Techniques for Real-Time Extraction and Analysis of Fetal and Maternal Electrocardiogram Signals.

This article presents an innovative approach to analyzing and extracting electrocardiogram (ECG) signals from the abdomen and thorax of pregnant women, with the primary goal of isolating fetal ECG (fECG) and maternal ECG (mECG) signals. To resolve the difficulties related to the low amplitude of the fECG, various noise sources during signal acquisition, and the overlapping of R waves, we developed a new method for extracting ECG signals using blind source separation techniques. This method is based on independent component analysis algorithms to detect and accurately extract fECG and mECG signals from abdomen and thorax data. To validate our approach, we carried out experiments using a real and reliable database for the evaluation of fECG extraction algorithms. Moreover, to demonstrate real-time applicability, we implemented our method in an embedded card linked to electronic modules that measure blood oxygen saturation (SpO2) and body temperature, as well as the transmission of data to a web server. This enables us to present all information related to the fetus and its mother in a mobile application to assist doctors in diagnosing the fetus's condition. Our results demonstrate the effectiveness of our approach in isolating fECG and mECG signals under difficult conditions and also calculating different heart rates (fBPM and mBPM), which offers promising prospects for improving fetal monitoring and maternal healthcare during pregnancy.

How the Soluble Human Leukocyte Antigen-G levels in Amniotic Fluid and Maternal Serum Correlate with the Feto-Placental Growth in Uncomplicated Pregnancies.

Introduction: Trophoblast-derived angiogenic factors are considered to play an important role in the pathophysiology of various complications of pregnancy. Human Leukocyte Antigen-G (HLA-G) belongs to the non-classical human major histocompatibility complex (MHC-I) molecule and has membrane-bound and soluble forms. HLA-G is primarily expressed by extravillous cytotrophoblasts located in the placenta between the maternal and fetal compartments and plays a pivotal role in providing immune tolerance. The aim of this study was to establish a relationship between concentrations of soluble HLA-G (sHLA-G) in maternal serum and amniotic fluid at 16-22 weeks of gestation and the sonographic measurements of fetal and placental growth. Materials and methods: sHLA-G in serum and amniotic fluid, as well as fetal biometric data and placental volume and perfusion indices, were determined in 41 singleton pregnancies with no complications. The level of sHLA-G (U/mL) was tested with a sandwich enzyme-linked immunosorbent assay (ELISA) kit. Results: The sHLA-G levels were unchanged both in amniotic fluid and serum during mid-pregnancy. The sHLA-G level in serum correlated positively with amniotic sHLA-G level (β = 0.63, p < 0.01). Serum sHLA-G level was significantly correlated with abdominal measurements (β = 0.41, p < 0.05) and estimated fetal weight (β = 0.41, p < 0.05). Conversely, amniotic sHLA-G level and placental perfusion (VI: β = -0.34, p < 0.01 and VFI: β = -0.44, p < 0.01, respectively) were negatively correlated. A low amniotic sHLA-G level was significantly associated with nuchal translucency (r = -0.102, p < 0.05). Conclusions: sHLA-G assayed in amniotic fluid might be a potential indicator of placental function, whereas the sHLA-G level in serum can be a prognostic factor for feto-placental insufficiency.

Changes in the indicators of hemodynamics and oxygen transport in patients with idiopathic pulmonary arterial hypertension depending on their survival

Background. Idiopathic pulmonary arterial hypertension (IPAH) is a severe disease that affects the vessels of the pulmonary circulation and leads to right ventricular failure and death of patients. Indicators of hemodynamics and oxygen transport play central role in the progression and development of the disease. Objective: to evaluate indicators of hemodynamics, oxygen transport. Materials and methods. The study included 124 patients with IPAH. They were divided into two groups: alive patients (group 1) and those who died (group 2). All of them underwent general clinical examinations, a 6-minute walk test, transthoracic and speckle tracking echocardiography, right heart catheterization, blood gas analysis and calculation of hemodynamic parameters. Results. We calculated and compared the right (RVSWI) (19.93 ± 7.84 vs. 16.47 ± 4.67 g·m·m–2, p = 0.009) and left ventricular stroke work index (LVSWI) (39.47 ± 10.53 vs. 35.92 ± 11.19 g·m·m–2, p = 0.036) and their ratio (RVSWI/LVSWI) (0.59 ± 0.16 vs. 0.46 ± ± 0.13, p = 0.008), right (RVPC) (97.00 ± 2.16 vs. 1.82 ± 1.04 g·m, p = 0.001) and left ventricular pump coefficient (LVPC) (5.36 ± 4.84 vs. 4.41 ± 2.15 g·m, p = 0.04) and their ratio (RVPC/LVPC) (0.54 ± 0.19 vs. 0.44 ± 0.11, p = 0.05) in both groups of patients. Also, we found differences in partial pressure of carbon dioxide (PaCO2) of venous blood (34.5 ± 5.1 vs. 40.2 ± 6.9 mm Hg, p = 0.02), partial pressure of oxygen (PaO2) of arterial blood (90.2 ± 15.1 vs. 78.9 ± 11.2 mm Hg; p = 0.01), arteriovenous oxygen difference (A-vO2) (4.5 ± 1.2 vs. 5.0 ± 0.8 ml/dL, p = 0.02) between both groups. Conclusions. RVSWI, LVSWI, RVSWI/LVSWI, RVPC, LVPC, RVPC/LVPC were significantly different between the groups. The use of the above hemodynamic parameters can help in a deeper understanding of the prognosis in IPAH patients. Performance of oxygen transport indicators (PaCO2, PaO2) and A-vO2 in IPAH patients provides a broader understanding of the status and prognosis of this disease.

Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury

Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7–8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE.

UNPREDICTABLE IDENTIFICATION OF A TITIN MUTATION IN A YOUNG PATIENT PRESENTING WITH INFLAMMATORY CARDIOMYOPATHY

Abstract Case Presentation A 23 years old patient, affected by type 1 diabetes, presented with fever, dyspnea and bilateral peripheral edemas. In the last week he received antibiotic treatment for a persistent dry cough and sore throat, and became symptomatic for exertional dyspnea from three days. His mother died at the age of 40 for sudden cardiac death. Blood pressure and oxygen saturation were normal: the ECG showed sinus tachycardia with symmetric negative T waves in all precordial leads. High sensitivity troponin T was 0.01 mcg/L (normal value &amp;lt; 0.014 mcg/L). All remaining blood tests were normal, except for CRP that was slightly elevated. His echocardiogram revealed left ventricular (LV) remodelling and dilation, severely reduced LV ejection fraction (LVEF 20%) with global hypokinesia, more pronounced at the level of the anterior wall, interventricular septum and apex and a dilated right ventricle (RV) with reduced systolic function. Cardiac magnetic resonance (CMR) confirmed severe biventricular disfunction (LVEF 19%; RVEF 23%) and showed a small area of subepicardial inferior junctional late gadolinium enhancement (LGE). The patient underwent an endomyocardial biopsy that showed a lymphocytic virus–negative myocarditis. Given his known type 1 diabetes, steroid treatment was not considered and anakinra was started. The patient was discharged after two weeks with a slight amelioration of the LV function (LVEF 27%), on optimal heart failure therapy and anakinra. At six months he was in NYHA class II and CMR showed slight reduction in LV dimensions and improvement of the LV and RV function (LVEF 39%; RVEF 45%), with no changes in the LGE pattern. A genetic test was performed and revealed two titin gene mutations, both categorized as likely pathogenic (TTN c.[11831T&amp;gt;A]; c.[72510_72517delGACAAATG]), responsible for a genetic form of dilated cardiomyopathy. Conclusion The present case suggests that in young patients presenting with clinical or histological diagnosis of myocarditis, genetic testing for cardiomyopathies should be considered especially in presence of a positive family history for sudden death or an incomplete recovery of the LV function at follow–up. Identification of a gene mutation in these patients allows a more tailored risk stratification of the index case and a proper management of the entire family.

CHRONIC INFECTION AND SEVERE MITRAL REGURGITATION: A TRICKY CASE REPORT

Abstract Background Techniques of mitral valve repair has improved in the last decades. Percutaneous approach is now a reliable and safe therapy in those patients with high surgical risk. Of note, the presence of implanted prothesis may increase the risk of endocarditis, especially in those patients experiencing recurrent infection. Case Summary We describe a case of a 75–year–old with medical history of chronic lymphedema. It was characterized by periodical episode (yearly) of cellulitis, with a rapid onset of fever (38.5–39° C), lasting for a few days after paracetamol therapy. Patients had severe mitral valve regurgitation due to prolapse of the posterior leaflet (P2). In December 2022, he had percutaneous edge–to–edge mitral valve. Three months later the patient was admitted to the emergency department of our hospital due to fever without any specific symptoms. The patient was well compensated, normal blood pressure, heart rate and oxygen saturation. He had emocolture which revealed the presence of Staphilococcus lugdunensis. Transesophageal echocardiogram confirmed the presence endocarditis, showing a huge (10x12 mm) vegetation at the level of mitral device (Fig 1 and 2). Patients was then referred to cardiac surgery for urgent mitral valve replacement with mitral bioprothesis (Fig 3). He was treated with ev antibiotic for six weeks after cardiac surgery. Additionally, chronic treatment with amoxicillin 500 mg/day was also prescribed at discharge. After six months follow–up, patients had no signs of endocarditis. Conclusion The management and treatment of chronic infection is of paramount importance to reduce the risk of prothesis infection procedure in patients needing a prothesis implantation. The last European Society of Cardiology guidelines on endocarditis do not provide any recommendation regarding a long–term treatment of patients with high risk of infection (i.e. due to chronic infection) and with an implanted cardiac device/prothesis. We believe this represents an important unmeet need.

HALF DOSE THROMBOLYSIS IN INTERMEDIATE – HIGH RISK PULMONARY EMBOLISM WITH TRICUSPID VALVE MOBILE MASS: A BAIL OUT STRATEGY

Abstract A 82–year–old previously healthy male was referred to the emergency department complaining sudden onset dyspnea and witnessed syncope complicated by head trauma. Recurrent dizziness occurred previously. No history or drug consumption noted. On admission: heart rate 90 beats/min, blood pressure 110/60 mmHg, respiratory rate 25 breaths/min, oxygen saturation 87% in room air, normal body temperature. No lower extremities tenderness or swelling reported. Consistent with peripheral blood oxygen saturation levels, arterial blood gas analysis showed hypoxemia and respiratory alkalosis. Laboratory exams were significant for thrombocytopenia (89.000 cells/L), elevated cardiac troponin T levels (222 ng/L) and natriuretic peptide (NT pro–BNP 3944 pg/mL). Head CT excluded acute cerebral hemorrhage. At the electrocardiogram, signs of RV strain were present (biphasic T–waves in V1–V3 leads, S1–Q3–T3). Transthoracic echocardiography (TTE) showed dilated RV with hypokinetic free wall, “D–shaped” LV, “60/60” sign and a mobile filiform mass crossing the tricuspid valve plan in the right atrium (fig. 1). The patient did not present structural valvular abnormalities or endocarditis–related risk factors. CT pulmonary angiography detected a “saddle” PE and extensive thrombosis in inferior vena cava. After unfractioned heparin (UFH) bolus, the patient was transferred to our intensive care unit and balancing risks and benefits the chosen treatment option consisted in half dose systemic thrombolysis (50 mg rtPA in 60’’; 10 mg as loading dose in 2’). Because of potential harmful effects in thrombocytopenia and recent head trauma, UFH was temporarily withheld and started again after 1 hour. The day after, a beside TTE showed complete tricuspid thrombus resolution, a significant decrease in RV/LV ratio and systolic pulmonary artery pressure (fig. 2). Apart from small hematomas, no bleedings were reported. The patient was shifted to the ward on the next day and following course was uneventful. On day 4 a direct oral anticoagulant (Dabigatran 110 mg) was started. Abdominal and inferior limb–deep–venous ultrasound were both negative for pathological reports. A total body CT was scheduled to exclude silent malignancies at discharge. Take home message: in intermediate–high risk PE, half dose systemic fibrinolysis strategy is controversial since its potential benefit is counterbalanced by concerns about major bleedings, but increasing data suggest its efficacy with low risk profile.

Prospective Evaluation of the Peripheral Perfusion Index in Assessing the Organ Dysfunction and Prognosis of Adult Patients With Sepsis in the ICU.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (β -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (β -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (β -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (β -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.