Arterial Blood Research Articles

Super-Resolving and Denoising 4D flow MRI of Neurofluids Using Physics-Guided Neural Networks.

To obtain high-resolution velocity fields of cerebrospinal fluid (CSF) and cerebral blood flow by applying a physics-guided neural network (div-mDCSRN-Flow) to 4D flow MRI. The div-mDCSRN-Flow network was developed to improve spatial resolution and denoise 4D flow MRI. The network was trained with patches of paired high-resolution and low-resolution synthetic 4D flow MRI data derived from computational fluid dynamic simulations of CSF flow within the cerebral ventricles of five healthy cases and five Alzheimer's disease cases. The loss function combined mean squared error with a binary cross-entropy term for segmentation and a divergence-based regularization term for the conservation of mass. Performance was assessed using synthetic 4D flow MRI in one healthy and one Alzheimer' disease cases, an in vitro study of healthy cerebral ventricles, and in vivo 4D flow imaging of CSF as well as flow in arterial and venous blood vessels. Comparison was performed to trilinear interpolation, divergence-free radial basis functions, divergence-free wavelets, 4DFlowNet, and our network without divergence constraints. The proposed network div-mDCSRN-Flow outperformed other methods in reconstructing high-resolution velocity fields from synthetic 4D flow MRI in healthy and AD cases. The div-mDCSRN-Flow network reduced error by 22.5% relative to linear interpolation for in vitro core voxels and by 49.5% in edge voxels. The results demonstrate generalizability of our 4D flow MRI super-resolution and denoising approach due to network training using flow patches and physics-based constraints. The mDCSRN-Flow network can facilitate MRI studies involving CSF flow measurements in cerebral ventricles and association of MRI-based flow metrics with cerebrovascular health.

Impact of Hyponatremia on COVID-19-Related Outcomes: A Retrospective Analysis

Background: Sodium disturbances are observed in one-third of patients with COVID-19 and result from multifaceted mechanisms. Notably, hyponatremia is associated with disease progression and mortality. Aim: We aimed to analyze the impact of hyponatremia on COVID-19 outcomes and its correlation with clinical and laboratory parameters during the first wave. Methods: We evaluated the sodium levels of 558 patients with COVID-19 between 21 March 2020, and 31 July 2020, at a single center. We performed linear regression analyses to explore the correlation of sodium levels with COVID-19-related outcomes, demographic data, signs and symptoms, and laboratory parameters. Next, we conducted Pearson correlation analyses. A p-value < 0.05 was considered significant. Results: Hyponatremia was found in 35.3% of hospitalized patients with COVID-19. This was associated with the need for intensive care transfer (B = −1.210, p = 0.009) and invasive mechanical ventilation (B = −1.063, p = 0.032). Hyponatremia was frequently found in oncologic patients (p = 0.002) and solid organ transplant recipients (p < 0.001). Sodium was positively associated with diastolic blood pressure (p = 0.041) and productive cough (p = 0.022) and negatively associated with dry cough (p = 0.032), anorexia (p = 0.004), and nausea/vomiting (p = 0.007). Regarding the correlation of sodium levels with other laboratory parameters, we observed a positive correlation with hematocrit (p = 0.011), lymphocytes (p = 0.010), pCO2 (p < 0.0001), bicarbonate (p = 0.0001), and base excess (p = 0.008) and a negative correlation with the neutrophil-to-lymphocyte ratio (p = 0.009), the platelet-to-lymphocyte ratio (p = 0.033), and arterial blood glucose (p = 0.016). Conclusions: Hyponatremia is a risk factor for adverse outcomes in COVID-19 patients. It is associated with demographic data and clinical and laboratory parameters. Therefore, hyponatremia is an important tool for risk stratification in COVID-19 patients.

Epidemiology of acute hypoxaemic respiratory failure in Australian and New Zealand intensive care units during 2005-2022. A binational, registry-based study.

Acute hypoxaemic respiratory failure (AHRF) is a common reason for intensive care unit (ICU) admission. However, patient characteristics, outcomes, and trends over time are unclear. We describe the epidemiology and outcomes of patients with AHRF over time. In this binational, registry-based study from 2005 to 2022, we included all adults admitted to an Australian or New Zealand ICU with an arterial blood gas within the first 24h of ICU stay. AHRF was defined as a partial pressure of oxygen/inspired oxygen ratio (PaO2/FiO2) ≤ 300. The primary outcome was adjusted in-hospital mortality, categorised based on PaO2/FiO2 (mild: 200-300, moderate: 100-200, and severe < 100, and non-linearly). We investigated how adjusted mortality evolved based on temporal trends (by year of admission), sex, age, admission diagnosis and the receipt of mechanical ventilation. Of 1,560,221 patients, 826,106 (52.9%) were admitted with or developed AHRF within the first 24h of ICU stay. Of these 826,106 patients, 51.4% had mild, 39.3% had moderate, and 9.3% had severe AHRF. Compared to patients without AHRF (5.3%), patients with mild (8%), moderate (14.2%) and severe (29.9%) AHRF had higher in-hospital mortality rates. As PaO2/FiO2 ratio decreased, adjusted in-hospital mortality progressively increased, particularly below an inflection point at a PaO2/FiO2 ratio of 200. The adjusted in-hospital mortality for all patients decreased over time (13.3% in 2005 to 8.2% in 2022), and this trend was similar in patients with and without AHRF. The healthcare burden due to AHRF may be larger than expected, and mortality rates remain high in severe AHRF. Although mortality has decreased over time, this may reflect improvements in ICU care in general, rather than specifically in AHRF. More research is required to earlier identify AHRF and stratify these patients at risk of deterioration early, and to validate our findings.

Can end-tidal CO2 measurement replace arterial partial CO2 in emergency department respiratory distress management?

ObjectiveTo assess the feasibility of using end-tidal carbon dioxide (EtCO2) as a non-invasive substitute for partial pressure of arterial carbon dioxide (PaCO2) in emergency department (ED) triage and follow-up, and to explore the potential of partial pressure of venous carbon dioxide (PvCO2) as an alternative to PaCO2. DesignProspective cross-sectional study. SettingTertiary university hospital. Patients or participants97 patients presenting with acute respiratory distress to the ED. InterventionsEtCO2, arterial blood gases, and venous blood gases measured at admission (0 min), 60 min, and 120 min. Main variables of interestCO2 levels. ResultsAmong 97 patients (mean age: 70.93 ± 9.6 years; 60.8% male), EtCO2 > 45 mmHg at admission showed strong positive correlations with PaCO2 and PvCO2 (r = 0.844, r = 0.803; p < 0.001, respectively). Significant positive correlation was observed between 60-min EtCO2 and PaCO2 (r = 0.729; p < 0.001). Strong correlation between PaCO2 and PvCO2 at 120 min when EtCO2 > 45 mmHg (r = 0.870; p < 0.001). EtCO2 was higher in hospitalized patients compared to discharged ones. ConclusionsEtCO2 appears promising as a substitute for PaCO2 in ED patients with acute respiratory distress within the initial two hours of treatment. Venous blood gas sampling offers a less invasive alternative to arterial sampling, facilitating simultaneous blood tests.

Umbilical arterial blood lactate as predictor of early neonatal outcome and evaluation of intrapartum asphyxia

BackgroundPerinatal asphyxia is a leading cause of under-5 mortality and exerts great pressure on the health system. Adequate foetal monitoring in labour is paramount in the early detection of foetal distress to prevent perinatal asphyxia. Several methods of foetal monitoring are in use with varying efficacy. This study investigated the efficacy of umbilical arterial (UA) lactate assay in predicting adverse perinatal outcomes. MethodologyThis was a prospective longitudinal study involving 160 pregnant women in the active phase of labour at term who met the inclusion criteria. They were recruited using a consecutive sampling technique and underwent a cardiotocography. Then they were classified into normal and abnormal cardiotocographic groups. At delivery, the UA blood of all of the babies was collected and assayed for serum lactate, and the levels were correlated with the perinatal outcome. The perinatal outcomes were measured by Apgar scores, admission into the neonatal unit, and hypoxic ischaemic encephalopathy. Analysis was done to determine the sensitivity and specificity of UA lactate in predicting birth asphyxia, hypoxic ischaemic encephalopathy, and neonatal unit admission. ResultsThe mean age ± standard deviation (SD) between the two cardiotocography (CTG) groups, normal years (30.55 ± 5.59) and abnormal years (29.86 ± 5.51), were similar. A critical UA lactate concentration >9.1 mmol/L predicted Apgar scores <7 at 5 min with a sensitivity and specificity of 76.47% (CI: 50.1–93.2) and 91.55% (CI: 85.7–95.6%), respectively. Also, the need for neonatal unit admission was predicted at a cut-off point >9.1 mmol/L with a sensitivity of 61.90% (CI: 38.4–81.9) and specificity of 91.30% (CI: 85.3–95.4). Umbilical artery lactate levels >11.2 mmol/L predicted the development of hypoxic ischaemic encephalopathy in neonates with a sensitivity of 100% (CI: 39.8–100.0) and specificity of 88.39% (CI: 82.3–93.0). ConclusionUmbilical artery lactate correlates with adverse pregnancy outcomes and is an excellent tool for predicting adverse neonatal outcome.

The effectiveness of low-load Blood flow restriction Exercise in patients with an acute Achilles tendon rupture treated Non-surgically (BEAN): Protocol for a randomized controlled trial

BackgroundBlood flow restriction exercise (BFRE) has been proposed as a viable method for preserving muscle mass and function after an injury during periods of load restrictions such as after an acute Achilles tendon rupture. However, its effectiveness and safety in patients with an Achilles tendon rupture have yet to be evaluated in a randomized trial. ObjectivesFirst, to investigate the effectiveness of early initiated BFRE in patients with non-surgically treated acute Achilles tendon rupture. Second, to evaluate whether it is better to apply BFRE in the beginning (1-12 weeks) or later (13-24 weeks) in the rehabilitation period. MethodsThis is an assessor-blinded, randomized, controlled multicenter trial with patients assigned in a 1:1 ratio to two parallel groups, that either receive BFRE in weeks 1-12 followed by usual care in weeks 13-24, or receive usual care in weeks 1-12 followed by BFRE in weeks 13-24. The BFRE program is performed three times weekly on the injured leg at 80% of the pressure required to fully restrict the arterial blood flow. Post-intervention tests are conducted in week 13, comparing early BFRE with usual care, and in week 25, comparing early BFRE with late BFRE. At the 13-week evaluation, the primary outcome is the Single-Leg Heel-Rise test which assesses the patient’s ability to raise the heel of the injured leg a minimum of 2cm. At the 25-week evaluation, the primary outcome is the Achilles tendon Total Rupture Score which assesses the patient’s self-reported symptoms and physical ability.

Detecting causalities between strongly coupled dynamical systems

A new version of the convergent cross mapping is proposed to detect causalities from records for strongly coupled nonlinear dynamical systems, where the mutual entropy is used to measure nonlinear correlations, and the time delay stability is adopted to filter out false identifications. Calculations on various deterministic dynamic systems show that it is applicable not only to strongly coupled systems but also to non-interacting systems influenced by a common environment. Compared with the original version of convergent cross mapping, under strong couplings our proposed method has significantly higher accuracy, and is more robust to coupling strength. As a typical example, it is used to detect the causal effects between arterial blood pressure (ABP) and intracranial pressure (ICP) of patients diagnosed with traumatic brain injury (TBI). A mono-directional causality from ICP to ABP is identified.

Isometric Fatigue Resistance of Lumbar Extensors and Cardiovascular Strain in Lower Back Pain Patients Are Associated with Angiotensin-Converting Enzyme and Tenascin-C Gene Polymorphisms

Background: We tested whether gene polymorphisms for angiotensin-converting enzyme (ACE, rs1799752) and tenascin-C (TNC, rs2104772) are associated with variability in fatigue resistance and metabolic strain during static lumbar exercise through interactions with chronic nonspecific lower back pain and habitual physical exercise levels (PA). Methods: Forty-eight patients and matched controls performed an isometric endurance test for lumbar extensors. Metabolic strain to longissimus muscle (oxygen saturation, lactate) and cardiovascular system (muscle hemoglobin, blood pressure) and holding time were monitored. Subjects were genotyped for rs1799752 (II, ID, DD) and rs2104772 (AA, AT, TT). Associations of variance with group, genotype, and PA were analyzed under a 5% false discovery rate. Results: The holding time was lower in patients than in controls (150.9 vs. 188.6 s). This difference was associated with both genotypes, as patients with DD-rs1799752-genotype (p = 0.007) and TT-rs2104772-genotype (p = 0.041) showed lower fatigue resistance. Muscle deoxygenation during exercise varied in positive association with the rs2104772-genotype and PA (p = 0.010, η2 = 0.236). Mean arterial blood pressure (p = 0.028, η2 = 0.108) and recovery of hemoglobin concentration (p = 0.003, η2 = 0.907) demonstrated complex group x rs2104772 interactions. Conclusions: Polymorphisms rs1799752 and rs2104772 influence back pain-related variability in lumbar fatigue resistance. rs2104772 was linked to cardiovascular strain during isometric exercise and recovery via muscle perfusion.

Hypercapnia during transcatheter aortic valve replacement under monitored anaesthesia care: a retrospective cohort study

BackgroundAcute intraoperative hypercapnia and respiratory acidosis, which can occur during monitored anaesthesia care (MAC), pose significant cardiopulmonary risks for patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). The...

Occurrence of Low Cardiac Index During Normotensive Periods in Cardiac Surgery: A Prospective Cohort Study Using Continuous Noninvasive Cardiac Output Monitoring.

Continuous cardiac output monitoring is not standard practice during cardiac surgery, even though patients are at substantial risk for systemic hypoperfusion. Thus, the frequency of low cardiac output during cardiac surgery is unknown. We conducted a prospective cohort study at a tertiary medical center from July 2021 to November 2023. Eligible patients were ≥18 undergoing isolated coronary bypass (CAB) surgery with the use of cardiopulmonary bypass (CPB). Cardiac output indexed to body surface area (CI) was continuously recorded at 5-second intervals throughout surgery using a US Food and Drug Administration (FDA)-approved noninvasive monitor from the arterial blood pressure waveform. Mean arterial blood pressure (MAP) and central venous pressure (CVP) were also analyzed. Low CI was defined as <2 L/min/m2 and low MAP as <65 mm Hg. We calculated time with low CI for each patient for the entire surgery, pre-CPB and post-CPB periods, and the proportion of time with low CI and normal MAP. We used Pearson correlation to evaluate the relationship between CI and MAP and paired Wilcoxon rank sum tests to assess the difference in correlations of CI with MAP before and after CPB. In total, 101 patients were analyzed (age [standard deviation, SD] 64.8 [9.8] years, 25% female). Total intraoperative time (mean [SD]) with low CI was 86.4 (62) minutes, with 61.2 (42) minutes of low CI pre-CPB and 25.2 (31) minutes post-CPB. Total intraoperative time with low CI and normal MAP was 66.5 (56) minutes, representing mean (SD) 69% (23%) of the total time with low CI; 45.8 (38) minutes occurred pre-CPB and 20.6 (27) minutes occurred post-CPB. Overall, the correlation (mean [SD]) between CI and MAP was 0.33 (0.31), and the correlation was significantly higher pre-CPB (0.53 [0.32]) than post-CPB (0.29 [0.28], 95% confidence interval [CI] for difference [0.18-0.34], P < .001); however, there was substantial heterogeneity among participants in correlations of CI with MAP before and after CPB. Secondary analyses that accounted for CVP did not alter the correlation between CI and MAP. Exploratory analyses suggested duration of low CI (C <2 L/min/m2) was associated with increased risk of postoperative acute kidney injury (odds ratios [ORs] = 1.09; 95% CI; 1.01-1.13; P = .018). In a prospective cohort of patients undergoing CAB surgery, low CI was common even when blood pressure was normal. CI and MAP were correlated modestly. Correlation was higher before than after CPB with substantial heterogeneity among individuals. Future studies are needed to examine the independent relation of low CI to postoperative kidney injury and other adverse outcomes related to hypoperfusion.

Epidemiology of supplemental oxygen in patients with pulmonary hypertension.

Patients with pulmonary hypertension (PH) may present with hypoxaemia at rest or during daily activities. There is no epidemiological data on the prescription of long-term oxygen therapy (LTOT) in patients with PH. The study sought to analyse the prevalence and incidence of LTOT prescription among patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) in Spain and to determine predictors for this prescription. A retrospective analysis was performed from the Spanish Registry of Pulmonary Arterial Hypertension (REHAP). Collected data included demographics and anthropometric measurements, functional class (FC), arterial blood gases, pulmonary function tests, haemodynamic measurements, six-minute walking distance (6MWD) and LTOT prescription. In addition, we assessed the prevalence and incidence of LTOT prescription by PH group and subtype and potential predictors for LTOT initiation in the first 5 years after diagnosis. We analysed 4533 patients (69.9% PAH and 30.1% CTEPH), mostly female (64.5%), with a mean age of 53.0 ± 18.3 years. The prevalence of LTOT was 19.3% for all patients. The incidence of LTOT prescriptions decreased from 5.6% to 1.6% between 2010 and 2019, respectively. Predictors for LTOT prescription, excluding those that represent the indication for oxygen therapy were: FC (HR: 1.813), 6MWD (HR: 1.002), mean pulmonary arterial pressure (mPAP) (HR: 1.014), cardiac index (CI) (HR: 1.253), pulmonary vascular resistance (PVR) (HR: 1.023) and diffusing capacity of carbon monoxide (DLCO) (HR: 1.294). The prevalence of LTOT in PAH and CTEPH patients is close to 20%. FC, 6MWD, mPAP, CI, PVR and DLCO were predictors for LTOT prescription.

Multimodal management of ruptured internal carotid artery blood blister-like aneurysm: technical notes and case series of surgical muscle wrapping and fenestration clipping combined with flow-diverter embolization

To evaluate the effects of a multimodal management technique combining surgical muscle wrapping, clipping, and flow-diverter stent (FDS) placement in patients with ruptured blood blister-like aneurysms (BBAs) in the internal carotid artery (ICA). In a retrospective case series review from 2020 to 2023, three patients with ruptured ICA BBAs underwent multimodal management, an approach combining muscle wrapping, surgical clipping, and FDS embolization. The aneurysm sac was initially packed and wrapped with multiple tailored temporalis muscle grafts and then secured using fenestration clips, with good preservation of the ICA branches. The FDS was placed 2-3 weeks after the clipping. All three patients had right ICA BBAs (mean age, 52 years). The modified Hunt and Hess grades ranged from 2 to 3, and the Fisher grades ranged from 3 to 4. The mean angiography follow-up time was 27.7 months (15, 31, and 37 months). There were no instances of symptomatic vasospasm or visible ischemic stroke during follow-up computed tomography. No patient required cerebrospinal fluid shunt implantation, and all achieved favorable neurological outcomes (modified Rankin Scale 0-1). Follow-up digital subtraction angiography revealed no evidence of aneurysm recurrence or significant ICA stenosis. We discuss a promising multimodal management approach for ruptured ICA BBAs combining muscle wrapping, surgical clipping, and FDS embolization. This technique was safe and effective in preventing re-rupture, achieving positive short-term clinical outcomes. Further research and more extensive studies are required to validate the long-term efficacy of this approach.

Docosahexaenoic acid insufficiency impairs placental angiogenesis by repressing the methylene-bridge fatty acylation of AKT in preeclampsia

IntroductionPreeclampsia (PE), characterised by hypertension in pregnancy, is regarded as a placental metabolism-related syndrome affecting 5–8% of pregnancies worldwide. The insufficiency of polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA), is a causative factor of PE pathogenesis. However, its molecular aetiology is yet to be comprehensively elucidated. MethodsCRISPR/Cas9 was used to construct Fads2 knockout mice. Gas chromatography–mass spectrometry was used to detect placental fatty acid levels. Gene Expression Omnibus was used to analyze placental FADS2 mRNA levels. CCK-8 assay was used to assess cell growth capacity. Cell migration and invasion abilities were measured by transwell and wound healing assay. Tube forming assay was used to test angiogenesis ability. The co-immunoprecipitation assay was used to validate interactions between two proteins. AKT inhibitor MK-2206 and methylene-bridge fatty acylation inhibitor tryptophan were used to rescue experiments. ResultsCompared to those in women with normal pregnancies, the DHA levels in the placentas of patients with PE decreased with the downregulation of FADS2, the key desaturase in the synthesis of PUFAs. Pregnant Fads2+/− mice exhibited PE-like symptoms, including proteinuria and elevated systolic arterial blood pressure, due to defective placental angiogenesis. Mechanistically, FADS2 knockdown in trophoblasts decreased cellular DHA levels and repressed the methylene-bridge fatty-acylation of AKT, inhibiting AKT-VEGFA signalling, which is crucial for angiogenesis. DiscussionOur results suggest that placental DHA insufficiency downregulates placental angiogenesis via inhibiting fatty acylating AKT and AKT-VEGFA signalling, a novel insight into abnormal fatty acid metabolism in PE.

Association between Bilateral Vertebral Artery Blood Flow Changes and Posterior Circulation Infarction in Patients with Severe Intracranial Stenosis.

To explore the association between net vertebral artery flow volume (NVAFV), calculated through color duplex ultrasonography (CDU), and posterior circulation infarction (PCI) in patients with severe intracranial vertebral artery (VA) stenosis. 234 patients with severe intracranial VA stenosis (≥70%) were categorized into the PCI group (n=139) and the non-PCI group (n=95) based on cranial MRI diagnosis, The correlation between NVAFV and CT perfusion (CTP) data was analyzed, and the occurrence of PCI under diverse PCI mechanisms was also investigated; Multifactorial logistic regression and Stratified analysis was performed to analyze the association between NVAFV and PCI. Lastly, generalized additive models and smooth curve fitting was utilized to outline relationship between NVAFV and PCI. NVAFV showed a significant correlation with cerebral blood flow (CBF), mean transmit Time (MTT) and time to peak (TTP); In the large artery atherosclerosis mechanism, a reduction in NVAFV correlated with a gradual rise in PCI cases (p = 0.002), while this trend lacked significance in the branch artery occlusive disease mechanism (p = 0.993); In the fully adjusted model, each 10 ml/min increase in NVAFV reduced PCI incidence by 11% (OR 0.890, 95%CI 0.840 to 0.943, p &lt; 0.001), Sensitivity analysis showed similar results; NVAFV presented different PCI risks among various glucose level subgroups, the OR (95%CI) for PCI was 0.788 (0.684, 0.906) in low-glucose group(T1), 0.968 (0.878, 1.066) in moderate-glucose group(T2) and 0.886 (0.801, 0.979) in high-glucose group(T3). Smooth curve fitting demonstrated a linear negative association between NVAFV and PCI. NVAFV demonstrated an association with PCI in patients with severe intracranial VA stenosis, it can serve as a reference for identifying high-risk populations of PCI, however, it must be considered in combination with glucose.

An end-to-end deep learning pipeline to derive blood input with partial volume corrections for automated parametric brain PET mapping

Dynamic 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (dFDG-PET) for human brain imaging has considerable clinical potential, yet its utilization remains limited. A key challenge in the quantitative analysis of dFDG-PET is characterizing a patient-specific blood input function, traditionally reliant on invasive arterial blood sampling. This research introduces a novel approach employing non-invasive deep learning model-based computations from the internal carotid arteries (ICA) with partial volume (PV) corrections, thereby eliminating the need for invasive arterial sampling. We present an end-to-end pipeline incorporating a 3D U-Net based ICA-net for ICA segmentation, alongside a Recurrent Neural Network (RNN) based MCIF-net for the derivation of a model-corrected blood input function (MCIF) with PV corrections. The developed 3D U-Net and RNN was trained and validated using a 5-fold cross-validation approach on 50 human brain FDG PET scans. The ICA-net achieved an average Dice score of 82.18% and an Intersection over Union of 68.54% across all tested scans. Furthermore, the MCIF-net exhibited a minimal root mean squared error of 0.0052. The application of this pipeline to ground truth data for dFDG-PET brain scans resulted in the precise localization of seizure onset regions, which contributed to a successful clinical outcome, with the patient achieving a seizure-free state after treatment. These results underscore the efficacy of the ICA-net and MCIF-net deep learning pipeline in learning the ICA structure’s distribution and automating MCIF computation with PV corrections. This advancement marks a significant leap in non-invasive neuroimaging.

Reinforcement Learning to Optimize Ventilator Settings for Patients on Invasive Mechanical Ventilation: A Retrospective Study.

One of the significant changes in intensive care medicine over the past two decades is the acknowledgement that improper mechanical ventilation settings substantially contribute to pulmonary injury in critically ill patients. Artificial intelligence (AI) solutions can be used to optimize mechanical ventilation settings in intensive care units (ICUs) and to improve patient outcomes. Specifically, machine learning algorithms can be trained on large datasets of patient information and mechanical ventilation settings. These algorithms can then predict patient responses to different ventilation strategies and suggest personalized ventilation settings for individual patients. In this study, we aimed to design and evaluate an AI solution that could tailor an optimal ventilator strategy for each critically ill patient who requires mechanical ventilation. We proposed a reinforcement learning-based AI solution using observational data from multiple ICUs in the US. The primary outcome was hospital mortality. Secondary outcomes were the proportion of optimal oxygen saturation and the proportion of optimal mean arterial blood pressure. We trained our AI agent to recommend low/medium/high levels of three ventilator settings - positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2) and ideal body weight-adjusted tidal volume - according to patients' health conditions. We defined a policy as a set of rules guiding ventilator setting changes given specific clinical scenarios. Off-policy evaluation metrics were applied to evaluate the AI policy. We studied 21,595 and 5,105 patients' ICU stays from the eICU Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases respectively. Using the learnt AI policy, we estimated the hospital mortality rate (eICU 12.1±3.1%; MIMIC-IV 29.1±0.9%), proportion of optimal oxygen saturation (eICU 58.7±4.7%; MIMIC-IV 49.0±1.0%), and proportion of optimal mean arterial blood pressure (eICU 31.1±4.5%; MIMIC-IV 41.2±1.0%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution outperformed observed clinical practice.We studied 21,595 5105 and 5,105 21595 patients' ' ICU stays from the Medical Information Mart for Intensive Care -IV (MIMIC-IV)(1) and eICU Collaborative Research (eICU) and Medical Information Mart for Intensive Care IV (MIMIC-IV) databases respectively. Observed hospital mortality rates were 18.2% (eICU) and 31.1% (MIMIC-IV). UsingFor the learnt AI policy, we estimated the hospital mortality rate (eICU 14.7±0.7%; MIMIC-IV 29.1±0.9%), proportion of optimal oxygen saturation (eICU 57.8±1.0%; MIMIC-IV 49.0±1.0%), and proportion of optimal mean arterial blood pressure (eICU 34.7 ± 1.0%; MIMIC-IV 41.2±1.0%). Based on multiple quantitative and qualitative evaluation metrics, our proposed AI solution has potential to outperformed observed clinical practice. Our study found that customizing ventilation settings for individual patients led to lower estimated hospital mortality rates compared to actual rates. This highlights the potential effectiveness of using RL methodology to develop AI models that analyze complex clinical data for optimizing treatment parameters. Additionally, our findings suggest the integration of this model into a clinical decision support system for refining ventilation settings, supporting the need for prospective validation trials.

The Respiratory Adjusted Shock Index at Admission Is a Valuable Predictor of In-Hospital Outcomes for Elderly Emergency Patients with Medical Diseases at a Japanese Community General Hospital.

Background: The respiratory adjusted shock index (RASI) is a risk score whose usefulness in patients with sepsis and trauma has previously been reported. However, its relevance in elderly emergency patients with medical diseases is yet to be clarified. This study assessed the usefulness of the RASI, which can be evaluated without requiring special equipment, to provide objective and rapid emergency responses. Methods: In this retrospective study, we recruited patients with medical diseases, aged 65 years or older, who were transported to the emergency room from Tokushima Prefectural Kaifu Hospital and underwent arterial blood gas testing from 1 January 2022 to 31 December 2023. We investigated the association of the RASI with other indices, including the lactate level, National Early Warning Score 2 (NEWS2), Shock Index (SI), Sequential Organ Failure Assessment (SOFA) score, quick SOFA (qSOFA) score, and systemic inflammatory response syndrome (SIRS). Results: In this study, we included 260 patients (mean age, 86 years), of whom 234 were admitted to the hospital; 27 and 49 patients died within 7 and 30 days of admission, respectively. The RASI was positively correlated with the lactate level, NEWS2, SI, and increase in the SOFA score (p < 0.001). The RASI was higher in patients with a SIRS or qSOFA score ≥ 2 than in those without (p < 0.001). It predicted death within 7 and 30 days of admission with an area under the curve (AUC) of 0.80 (95% confidence interval [CI]: 0.73-0.87), sensitivity of 96.3%, and specificity of 53.6% when the cutoff value was set to 1.58 and with an AUC of 0.73 (95% CI: 0.66-0.81), sensitivity of 69.4%, and specificity of 70.6% when the cutoff value was set to 1.83, respectively. Conclusions: The RASI is a simple indicator that can be used for predicting in-hospital outcomes in elderly emergency patients with medical diseases. Larger prospective studies based on this study are needed.

3-methoxycatechol causes vasodilation likely via KV channels: ex vivo, in silico docking and in vivo study

Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats. In the current study, we aimed at testing of its 22 structural congeners in order to find the most potent structure and to investigate the mechanism of action. 3-methoxycatechol (3-MOC), 4-ethylcatechol, 3,5-dichlorocatechol, 4-tert-butylcatechol, 4,5-dichlorocatechol, 3-fluorocatechol, 3-isopropylcatechol, 3-methylcatechol and the parent 4-methylcatechol exhibited high vasodilatory activities on isolated rat aortic rings with EC50s ranging from ∼10 to 24 μM. Some significant sex-differences were found. The most potent compound, 3-MOC, relaxed also resistant mesenteric artery but not porcine coronary artery, and decreased arterial blood pressure in both male and female spontaneously hypertensive rats in vivo without affecting heart rate. It potentiated the vasodilation mediated by cAMP and cGMP, but did not impact L-type Ca2+-channels. By using two inhibitors, activation of voltage-gated potassium channels (KV) was found to be involved in the mechanism of action. This was corroborated by docking analysis of 3-MOC with the KV7.4 channel. None of the most active catechols decreased the viability of the A-10 rat embryonic thoracic aorta smooth muscle cell line. Our findings showed that various catechols can relax vascular smooth muscles and hence could provide templates for developing new antihypertensive vasodilator agents without affecting coronary circulation.

Chest X-ray Findings and Prognostic Factors in Survival Analysis in Peritoneal Dialysis and Hemodialysis Patients: A Retrospective Cross-Sectional Study.

Background and Objectives: This study aims to analyze survival in peritoneal and hemodialysis patients using chest radiography and biochemical parameters, determine common dialysis etiologies and causes of death, reveal prognostic factors, and contribute to clinical practice. Materials and Methods: A retrospective cross-sectional study was conducted with data from 33 peritoneal dialysis and 37 hemodialysis patients collected between October 2018 and February 2020. Survival and mortality were retrospectively tracked over 70 months (October 2018-June 2024). Chest X-ray measurements (cardiothoracic index, pulmonary vascular pedicle width, right pulmonary artery diameter, diaphragmatic height) and biochemical parameters (urea, albumin, creatinine, parathormone, ferritin, hemoglobin, arterial blood gas, potassium) were analyzed for their impact on survival. Statistical analyses included descriptive statistics, chi-square test, Fisher's exact test, Bayesian analysis, McNemar test, Kaplan-Meier survival analysis, Cox regression, Bayesian correlation test, linear regression analysis (scatter plot), and ROC analysis. SPSS 20.0 was used for data analysis, with p < 0.05 considered statistically significant. Results: Hypertension, type 2 diabetes, and urogenital disorders were the main dialysis etiologies. Peritonitis (38.5%) and cardiovascular diseases (47.4%) were the leading causes of death in peritoneal and hemodialysis patients, respectively. Significant chest X-ray differences included pulmonary vascular pedicle width and pulmonary artery diameter in hemodialysis and diaphragm height in peritoneal dialysis. Kaplan-Meier showed no survival difference between methods. Cox regression identified age, intact parathormone levels, iPTH/PVPW ratio, and clinical status as survival and mortality factors. The iPTH/PVPW ratio cut-off for mortality prediction was ≤6.8. Conclusions: Age, intact parathormone levels, pulmonary vascular pedicle width, and clinical status significantly impact survival in dialysis patients. Management of hypertension and diabetes, management and follow-up of urogenital disorders, infection control, patient education, and regular cardiovascular check-ups may improve survival rates. Additionally, the iPTH/PVPW ratio can predict mortality risk.

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.