Ramipril After Transcatheter Aortic Valve Implantation in Patients Without Reduced Ejection Fraction: The RASTAVI Randomized Clinical Trial.

BACKGROUND: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation. METHODS AND RESULTS: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group (P=0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P=0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P=0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis. CONCLUSIONS: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

A critical role for HNF4α in polymicrobial sepsis-associated metabolic reprogramming and death.

In sepsis, limited food intake and increased energy expenditure induce a starvation response, which is compromised by a quick decline in the expression of hepatic PPARα, a transcription factor essential in intracellular catabolism of free fatty acids. The mechanism upstream of this PPARα downregulation is unknown. We found that sepsis causes a progressive hepatic loss-of-function of HNF4α, which has a strong impact on the expression of several important nuclear receptors, including PPARα. HNF4α depletion in hepatocytes dramatically increases sepsis lethality, steatosis, and organ damage and prevents an adequate response to IL6, which is critical for liver regeneration and survival. An HNF4α agonist protects against sepsis at all levels, irrespectively of bacterial loads, suggesting HNF4α is crucial in tolerance to sepsis. In conclusion, hepatic HNF4α activity is decreased during sepsis, causing PPARα downregulation, metabolic problems, and a disturbed IL6-mediated acute phase response. The findings provide new insights and therapeutic options in sepsis.

Infusion of sodium DL-3-ß-hydroxybutyrate decreases cerebral injury biomarkers after resuscitation in experimental cardiac arrest.

AIMS: Cerebral complications after cardiac arrest (CA) remain a major problem worldwide. The aim was to test the effects of sodium-ß-hydroxybutyrate (SBHB) infusion on brain injury in a clinically relevant swine model of CA. RESULTS: CA was electrically induced in 20 adult swine. After 10 min, cardiopulmonary resuscitation was performed for 5 min. After return of spontaneous circulation (ROSC), the animals were randomly assigned to receive an infusion of balanced crystalloid (controls, n = 11) or SBHB (theoretical osmolarity 1189 mOsm/l, n = 8) for 12 h. Multimodal neurological and cardiovascular monitoring were implemented in all animals. Nineteen of the 20 animals achieved ROSC. Blood sodium concentrations, osmolarity and circulating KBs were higher in the treated animals than in the controls. SBHB infusion was associated with significantly lower plasma biomarkers of brain injury at 6 (glial fibrillary acid protein, GFAP and neuron specific enolase, NSE) and 12 h (neurofilament light chain, NFL, GFAP and NSE) compared to controls. The amplitude of the stereoelectroencephalograph (sEEG) increased in treated animals after ROSC compared to controls. Cerebral glucose uptake was lower in treated animals. CONCLUSIONS: In this experimental model, SBHB infusion after resuscitated CA was associated with reduced circulating markers of cerebral injury and increased sEEG amplitude.

A multimodal group-based immersive virtual reality intervention for improving cognition and mental health in patients with post-covid-19 condition. A quasi-experimental design study.

Introduction: Adults with Post-COVID-19 Condition (PCC) may show cognitive impairments in attention, processing speed, memory, and executive function. Multimodal programs that combine cognitive training, physical activity and emotional tasks, such as mindfulness-based interventions (MBIs), may offer a suitable alternative for improving PCC treatments. Immersive Virtual Reality (IVR) is a promising technology that can enhance traditional cognitive training, physical activity, and MBIs. The use of IVR technology may increase engagement with these interventions and potentially enhance the individual benefits of cognitive training, exercise and MBIs. The current study evaluated the impact of a multimodal IVR intervention, comparing this with a usual care intervention (control group), in order to assess changes in cognition and mental health in adults with PCC. We also aimed to assess user experience factors such as enjoyment, perceived improvement, and fatigue following each multimodal IVR session within the experimental group. Method: Thirty-one participants with PCC symptoms were assigned to either the experimental group (IVR, n = 15) or the control group (usual care intervention, n = 16) in a quasi-experimental design study. The multimodal IVR intervention consisted of MBI, cognitive training and physical exercise and was delivered in a 60-min group session with 5 participants, twice a week, for 8 weeks (16 sessions in total). Measures of global cognition, attention, processing speed, verbal episodic memory and subjective memory complaints (primary measures), and depressive and anxiety symptoms and fatigue (secondary measures) were assessed at baseline and also after 8 weeks (post-intervention). Results: Mixed between-group (group) and within-group (pre-post assessments) ANOVAs revealed significant group*time interactions in global cognition, simple attention, processing speed, memory and depressive symptoms, with large effect sizes (p < 0.05; partial η2 > 0.14). There was also a marginally significant group*time interaction for executive function (p = 0.05). Follow-up analyses comparing pre-and post-intervention outcomes for each group separately showed that the experimental group significantly improved in global cognition, processing speed, memory and depressive symptoms, while the control group showed no significant pre-post changes. Friedman tests showed a significant main effect of time (χ2(2) = 6.609, p = 0.04), with a gradual increase in enjoyment from the first, to the mid, and then to the final session. In addition, perceived improvement scores remained high throughout the intervention, and patient-reported fatigue levels did not fluctuate significantly throughout the intervention. Conclusion: To our knowledge, no previous research has combined cognitive training, physical exercise and MBI using an IVR paradigm in adults with PCC. Despite their inherent limitations, our findings mark a pioneering step toward improving cognition and mental health outcomes in PCC through the innovative use of new technology and multimodal approaches. This first study should be accompanied by more extensive, randomized clinical trials aimed at further exploring and refining these interventions.

Mitral Transcatheter Edge-to-Edge Repair and Clinical Value of Novel Echocardiographic Biomarkers: A Hypothesis-Generating Study.

BACKGROUND: Longitudinal data on reverse cardiac remodeling and outcomes after transcatheter edge-to-edge repair (TEER) are limited. METHODS: A total of 78 patients with severe mitral regurgitation (MR) were included retrospectively. All patients had echocardiography at baseline and again six months after TEER. They were monitored for a primary composite endpoint, consisting of heart failure hospitalization and cardiovascular death, over 13 months. RESULTS: Significant decreases in the left ventricular ejection fraction (LVEF), all myocardial work indices (except global wasted work), and the left atrial reservoir were observed after TEER. Additionally, there was a decrease in the pulmonary artery systolic pressure and an increase in the tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio. A post-TEER TAPSE/PASP ratio of <0.47 (HR: 4.76, p-value = 0.039), and a post-TEER left atrial reservoir of <9.0% (HR: 2.77, p-value = 0.047) were associated with the primary endpoint. CONCLUSIONS: Echocardiography post-TEER reflects impairment in ventricular performance due to preload reduction and right ventricle and pulmonary artery coupling improvement. Short-term echocardiography after TEER identifies high-risk patients who could benefit from a close clinical follow-up. The prognostic significance of LA strain and the TAPSE/PASP ratio should be validated in subsequent large-scale prospective studies.

The Moderating Effect of Suggestibility on the Relationship between Body Mass Index and Body Dissatisfaction in Women.

Background: Body dissatisfaction (BD) has been consistently linked to adverse consequences on mental health and overall well-being, and is recognized as a significant contributing factor in the initiation and persistence of eating disorders (EDs). Empirical evidence has demonstrated that an elevated body mass index (BMI) and media influence and pressure about a thin ideal heighten the risk of subsequent BD. Moreover, suggestibility, a propensity to accept and act upon messages without critical evaluation, has been shown to be positively associated with greater susceptibility to the influence of sociocultural messages that endorse the thin ideal. This study aimed to assess whether suggestibility moderates the association between BMI and BD in women. Methods: A total of 117 women completed assessments using the Eating Disorder Inventory-3 (EDI-3) BD subscale and the Suggestibility Inventory, which encompasses a general suggestibility index and a subscale that evaluates susceptibility to influence by others. We conducted moderation analyses employing the PROCESS macro, with BMI as the central predictor, BD as the outcome variable, and suggestibility and its subscale as moderators. Results: The findings revealed statistically significant positive moderating interactions for both the general suggestibility index and susceptibility to influence by others. Specifically, women who exhibited high levels of suggestibility and susceptibility to influence by others demonstrated a more pronounced increase in BD as their BMI increased. Conclusions: These outcomes are in line with the sociocultural model of EDs, suggesting that greater susceptibility to external influences amplifies the impact of societal pressures to conform to thin ideals.

Immersive Virtual Reality Cognitive Training for Improving Cognition and Depressive Symptoms Among Older Adults. Current Evidence and Future Recommendations. A Systematic Review.

Older adults, particularly impacted by the pandemic, are anticipated to face considerable challenges to their cognitive and psychological health. Various cognitive training methods have been proposed to improve their cognitive decline through regular practice. Immersive virtual reality (IVR) offers a promising avenue to bolster cognitive and mental health care accessibility for older adults and has shown potential in augmenting traditional cognitive training methods. This systematic review aims to assess the efficacy of IVR-based cognitive training on improving cognitive impairments and depressive symptoms among older adults, irrespective of their level of cognitive decline. Systematic searches were conducted across MEDLINE-PubMed, EMBASE, and Web of Science databases from inception to December 2022. Only peer-reviewed articles reporting results from randomized controlled trials and pilot studies, focusing on the effects of VR-based cognitive training on adults aged 55 or older, were deemed eligible. Using the Cochrane Handbook for Systematic Reviews of Interventions, the risk of bias was appraised for each selected study. Out of 3,835 studies identified, 9 met the inclusion criteria. The qualitative analyses concluded that IVR cognitive training interventions enhanced certain cognitive functions and well-being among older adults, notably those with mild cognitive impairments. These interventions were particularly effective in boosting memory, visuospatial abilities, and measures related to depressive symptoms and overall well-being. However, enhancements were less pronounced for executive functions, attention, and global cognition. Based on these findings, we propose a set of tailored, inclusive, and evidence-based recommendations to adapt emerging technologies to better accommodate the needs of older adults.

Inhibition of circulating dipeptidyl-peptidase 3 by procizumab in experimental septic shock reduces catecholamine exposure and myocardial injury.

BACKGROUND: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. METHODS: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65-75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin-angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. RESULTS: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. CONCLUSIONS: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling.

Impaired angiotensin II signaling in septic shock.

Recent years have seen a resurgence of interest for the renin-angiotensin-aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II-angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin-angiotensin-aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin-angiotensin-aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin-angiotensin-aldosterone system alterations in septic shock should help to decipher patients' phenotypes and to implement targeted interventions.

Incidence of acute kidney injury and attributive mortality in acute respiratory distress syndrome randomized trials.

PURPOSE: The development of acute kidney injury (AKI) after the acute respiratory distress syndrome (ARDS) reduces the chance of organ recovery and survival. The purpose of this study was to examine the AKI rate and attributable mortality in ARDS patients. METHODS: We performed an individual patient-data analysis including 10 multicenter randomized controlled trials conducted over 20 years. We employed a Super Learner ensemble technique, including a time-dependent analysis, to estimate the adjusted risk of AKI. We calculated the mortality attributable to AKI using an inverse probability of treatment weighting estimator integrated with the Super Learner. RESULTS: There were 5148 patients included in this study. The overall incidence of AKI was 43.7% (n = 2251). The adjusted risk of AKI ranged from 38.8% (95% confidence interval [CI], 35.7 to 41.9%) in ARMA, to 55.8% in ROSE (95% CI, 51.9 to 59.6%). 37.1% recovered rapidly from AKI, with a significantly lower recovery rate in recent trials (P < 0.001). The 90-day excess in mortality attributable to AKI was 15.4% (95% CI, 12.8 to 17.9%). It decreased from 25.4% in ARMA (95% CI, 18.7 to 32%), to 11.8% in FACTT (95% CI, 5.5 to 18%) and then remained rather stable over time. The 90-day overall excess in mortality attributable to acute kidney disease was 28.4% (95% CI, 25.3 to 31.5%). CONCLUSIONS: The incidence of AKI appears to be stable over time in patients with ARDS enrolled in randomized trials. The development of AKI remains a significant contributing factor to mortality. These estimates are essential for designing future clinical trials for AKI prevention or treatment.

Specific and Non-specific Aspects and Future Challenges of ICU Care Among COVID-19 Patients with Obesity: A Narrative Review.

PURPOSE OF REVIEW: Since the end of 2019, the coronavirus disease 2019 (COVID-19) pandemic has infected nearly 800 million people and caused almost seven million deaths. Obesity was quickly identified as a risk factor for severe COVID-19, ICU admission, acute respiratory distress syndrome, organ support including mechanical ventilation and prolonged length of stay. The relationship among obesity; COVID-19; and respiratory, thrombotic, and renal complications upon admission to the ICU is unclear. RECENT FINDINGS: The predominant effect of a hyperinflammatory status or a cytokine storm has been suggested in patients with obesity, but more recent studies have challenged this hypothesis. Numerous studies have also shown increased mortality among critically ill patients with obesity and COVID-19, casting doubt on the obesity paradox, with survival advantages with overweight and mild obesity being reported in other ICU syndromes. Finally, it is now clear that the increase in the global prevalence of overweight and obesity is a major public health issue that must be accompanied by a transformation of our ICUs, both in terms of equipment and human resources. Research must also focus more on these patients to improve their care. In this review, we focused on the central role of obesity in critically ill patients during this pandemic, highlighting its specificities during their stay in the ICU, identifying the lessons we have learned, and identifying areas for future research as well as the future challenges for ICU activity.

VirtualPain. Preliminary findings from a group-based digital therapeutics intervention for fibromyalgia.

Introduction: Fibromyalgia (FM) is a disorder characterized by chronic pain, with significant medical, psychological, and socio-economic implications. Although there is limited evidence, cognitive-behavioral therapy (CBT) has shown to be effective in improving FM symptoms. An alternative to enhance CBT effectiveness is to incorporate digital therapeutics (DTx). Aim: We conducted a pilot study to investigate whether the addition of a DTx intervention (VirtualPain) to cognitive-behavioral group therapy (CBGT) can reduce pain perception and associated symptoms in patients with FM. Method: Ten patients with FM were initially recruited from a public hospital in Barcelona. The treatment consisted of 6 weeks of VirtualPain group sessions and 16 weeks of CBGT. Measures of catastrophizing, self-efficacy, and coping were recorded before, during, and after the protocol. In the DTx sessions, pain intensity was recorded before and after each session. Results: The program (DTx and CBGT) showed a significant improvement in pain-related self-efficacy and relaxation measures. Improvement in pain perception was observed only after the DTx intervention. Conclusions: This study provides preliminary results regarding the added value of DTx (VirtualPain) as part of a CBGT for FM. The use of the program has facilitated a significant reduction in pain perception in each of the VirtualPain sessions, which provides further evidence of how this technology can be beneficial for improving FM treatments.

Exploring Attentional Bias toward Alcohol Content: Insights from Eye-Movement Activity.

INTRODUCTION: Attentional bias (AB) is an implicit selective attention toward processing disorder-significant information while neglecting other environmental cues. Considerable empirical evidence highlights the clinical implication of AB in the onset and maintenance of substance use disorder. An innovative method to explore direct measures of AB relies on the eye-movement activity using technologies like eye-tracking (ET). Despite the growing interest regarding the clinical relevance of AB in the spectrum of alcohol consumption, more research is needed to fully determine the AB patterns and its transfer from experimental to clinical applications. The current study consisted of three consecutive experiments. The first experiment aimed to design an ad-hoc visual attention task (VAT) consisting of alcohol-related and neutral images using a nonclinical sample (n = 15). The objective of the second and third experiments was to analyze whether the effect of type of image (alcohol-related vs. neutral images) on AB toward alcohol content using the VAT developed in the first experiment was different for type of drinker (light vs. heavy drinker in the second experiment [n = 30], and occasional social drinkers versus alcohol use disorder (AUD) patients in the third experiment [n = 48]). METHODS: Areas of interest (AOIs) within each type of image (neutral and alcohol-related) were designed and raw ET-based data were subsequently extracted through specific software analyses. For experiment 1, attention maps were created and processed for each image. For experiments 2 and 3, data on ET variables were gathered and subsequently analyzed through a two-way ANOVA with the aim of examining the effects of the type of image and drinker on eye-movement activity. RESULTS: There was a statistically significant interaction effect between type of image and type of drinker (light vs. heavy drinker in experiment 2, F(1, 56) = 13.578, p < 0.001, partial η2 = 0.195, and occasional social drinker versus AUD patients in the experiment 3, F(1, 92) = 35.806, p < 0.001, partial η2 = 0.280) for "first fixation" with large effect sizes, but not for "number of fixations" and "dwell time." The simple main effect of type of image on mean "first fixation" score for AUD patients was not statistically significant. CONCLUSION: The data derived from the experiments indicated the importance of AB in sub-clinical populations: heavy drinkers displayed an implicit preference for alcohol-related images compared to light drinkers. Nevertheless, AB fluctuations in patients with AUD compared to the control group were found. AUD patients displayed an early interest in alcohol images, followed by an avoidance attentional processing of alcohol-related images. The results are discussed in light of recent literature in the field.

The alternative renin-angiotensin system in critically ill patients: pathophysiology and therapeutic implications.

The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and the cardio-renal system. The classical RAS, mainly mediated by angiotensin I, angiotensin-converting enzyme, and angiotensin II, has been reported to be altered in critically ill patients, such as those in vasodilatory shock. However, recent research has highlighted the role of some components of the counterregulatory axis of the classical RAS, termed the alternative RAS, such as angiotensin-converting Enzyme 2 (ACE2) and angiotensin-(1-7), or peptidases which can modulate the RAS like dipeptidyl-peptidase 3, in many critical situations. In cases of shock, dipeptidyl-peptidase 3, an enzyme involved in the degradation of angiotensin and opioid peptides, has been associated with acute kidney injury and mortality and preclinical studies have tested its neutralization. Angiotensin-(1-7) has been shown to prevent septic shock development and improve outcomes in experimental models of sepsis. In the context of experimental acute lung injury, ACE2 activity has demonstrated a protective role, and its inactivation has been associated with worsened lung function, leading to the use of active recombinant human ACE2, in preclinical and human studies. Angiotensin-(1-7) has been tested in experimental models of acute lung injury and in a recent randomized controlled trial for patients with COVID-19 related hypoxemia. Overall, the alternative RAS appears to have a role in the pathogenesis of disease in critically ill patients, and modulation of the alternative RAS may improve outcomes. Here, we review the available evidence regarding the methods of analysis of the RAS, pathophysiological disturbances of this system, and discuss how therapeutic manipulation may improve outcomes in the critically ill.

Neutralization of extracellular histones by sodium-Β-O-methyl cellobioside sulfate in septic shock.

BACKGROUND: Extracellular histones have been associated with severity and outcome in sepsis. The aim of the present study was to assess the effects of sodium-ß-O-Methyl cellobioside sulfate (mCBS), a histone-neutralizing polyanion, on the severity and outcome of sepsis in an experimental model. METHODS: This randomized placebo-controlled experimental study was performed in 24 mechanically ventilated female sheep. Sepsis was induced by fecal peritonitis. Animals were randomized to three groups: control, early treatment, and late treatment (n = 8 each). mCBS was given as a bolus (1 mg/kg) followed by a continuous infusion (1 mg/kg/h) just after sepsis induction in the early treatment group, and 4 h later in the late treatment group. Fluid administration and antimicrobial therapy were initiated 4 h T4 after feces injection, peritoneal lavage performed, and a norepinephrine infusion titrated to maintain mean arterial pressure (MAP) between 65-75 mmHg. The experiment was blinded and lasted maximum 24 h. RESULTS: During the first 4 h, MAP remained > 65 mmHg in the early treatment group but decreased significantly in the others (p < 0.01 for interaction, median value at T4: (79 [70-90] mmHg for early treatment, 57 [70-90] mmHg for late treatment, and 55 [49-60] mmHg for the control group). mCBS-treated animals required significantly less norepinephrine to maintain MAP than controls (p < 0.01 for interaction) and had lower creatinine (p < 0.01), lactate (p < 0.01), and interleukin-6 (p < 0.01) levels, associated with reduced changes in H3.1 nucleosome levels (p = 0.02). Early treatment was associated with lower norepinephrine requirements than later treatment. Two control animals died; all the mCBS-treated animals survived. CONCLUSIONS: Neutralization of extracellular histones with mCBS was associated with reduced norepinephrine requirements, improved tissue perfusion, less renal dysfunction, and lower circulating IL-6 in experimental septic shock and may represent a new therapeutic approach to be tested in clinical trials.

The role of renin-angiotensin system in sepsis-associated acute kidney injury: mechanisms and therapeutic implications.

PURPOSE OF REVIEW: This review aims to explore the relationship between the renin angiotensin system (RAS) and sepsis-associated acute kidney injury (SA-AKI), a common complication in critically ill patients associated with mortality, morbidity, and long-term cardiovascular complications. Additionally, this review aims to identify potential therapeutic approaches to intervene with the RAS and prevent the development of AKI. RECENT FINDINGS: Recent studies have provided increasing evidence of RAS alteration during sepsis, with systemic and local RAS disturbance, which can contribute to SA-AKI. Angiotensin II was recently approved for catecholamine resistant vasodilatory shock and has been associated with improved outcomes in selected patients. SUMMARY: SA-AKI is a common condition that can involve disturbances in the RAS, particularly the canonical angiotensin-converting enzyme (ACE) angiotensin-II (Ang II)/angiotensin II receptor 1 (AT-1R) axis. Increased renin levels, a key enzyme in the RAS, have been shown to be associated with AKI and may also guide vasopressor therapy in shock. In patients with high renin levels, angiotensin II administration may reduce renin concentration, improve intra-renal hemodynamics, and enhance signaling through the angiotensin II receptor 1. Further studies are needed to explore the role of the RAS in SA-AKI and the potential for targeted therapies.

Body Dissatisfaction and Body-Related Attentional Bias: Is There a Causal Relationship?

Previous research has shown an association between body dissatisfaction and attentional biases toward the body, but the nature of this relationship is not clear. It is possible that dissatisfaction causes attentional bias or that dissatisfaction is a result of such bias. To clarify the causal relationship between these two variables, this study manipulated dissatisfaction in a sample of healthy women by exposing them to images of "ideal" bodies and observed whether this manipulation increased attentional biases toward different body parts. Fifty-seven women took part in a pre-post experimental design in which they observed an avatar representing themselves in a virtual mirror before and after being exposed to "thin ideal" photographs. Eye-tracking technology was employed to quantify the frequency and duration of fixations on weight-related and weight-unrelated body parts. The outcomes revealed a successful induction of body dissatisfaction, leading participants to display a heightened number of fixations and prolonged fixation durations on unrelated-weight body parts. These findings remained significant after controlling for the effects of trait body dissatisfaction and body mass index. The results imply that heightened body dissatisfaction fosters the aversion of attention from weight-related body parts, which may function as a protective mechanism for preserving self-esteem and promoting psychological well-being.

Attentional Bias Modification Training Based on Virtual Reality and Eye Tracking in Anorexia Nervosa Patients.

Anorexia nervosa (AN) patients exhibit attentional bias (AB) related to the body, which is the tendency to pay greater attention to weight-related body areas compared to non-weight-related ones. This phenomenon has been linked to elevated levels of body dissatisfaction (BD) and may potentially reduce the effectiveness of body exposure therapy. The purpose of this pilot study is to assess the efficacy of a single session of a new body-related AB modification task (ABMT) that combines virtual reality with eye tracking in patients with AN. The goals of the ABMT are to reduce body-related AB by balancing attention between weight and non-weight-related body areas and to reduce BD levels. Twenty-three adolescent patients with AN were embodied in a virtual avatar and immersed in a virtual environment where they completed the ABMT. Body-related AB measures and BD levels were assessed before and after the training. A paired samples t-test showed statistically significant differences between pre-assessment and post-assessment; the complete fixation time on weight-related body parts was reduced and BD levels decreased. The initial evidence of the efficacy of this ABMT has important clinical implications, since AB and BD are considered risk factors for developing and maintaining eating disorder symptomatology among patients with AN.

Development of quantitative detection method for mass spectrometry coupled to an infrared laser spectroscope (Picarro) to monitor in nitrogen matrix a complex gas mixture of H2 , He, CO, N2 , Ne, O2 , Ar, CO2 , H2 S, CH4 , C2 H4 , C2 H6 , C3 H6 , C3 H8 , i-C4 H10 , n-C4 H10 , and C5 H12.

RATIONALE: The deep geological repository is considered the international reference for radioactive waste management. All gas exchanges must be understood in the context of the feasibility of such a repository. The technological challenge is to continuously monitor a wide range of gaseous molecules at low concentrations in confined spaces. METHODS: A gas monitoring station, composed of two complementary analyzers, was developed: an electron impact quadrupole mass spectrometer (HPR-20 R&D Hiden Analytical) and an infrared laser spectroscope (Picarro). The spectrometer was calibrated using simple mixtures (i.e., C2 H6 in N2 ) and multiple mixtures (i.e., H2 , He, CO2 , CH4 , and O2 in N2 ) at different concentrations to correct interferences. A matrix calculation is proposed to calculate the relative concentrations. RESULTS: The method developed allows the measurement of gaseous species: light hydrocarbons, noble gases, sulfides, greenhouse gases, oxygen, hydrogen, and nitrogen in the same mixture. For each gas, the SDs and the limits of detection and quantification were calculated. The method was validated by comparing the concentrations of the measured gas species with the reference values of two standard gas cylinders. CONCLUSIONS: Calibration of a complex gas mixture remains a challenge because fragmentation of molecules, especially hydrocarbons, reduces the sensitivity of the method. The method developed is suitable for continuous gas monitoring in a confined environment and can be implemented to perform experiments in underground structures: galleries, microtunnels (cells), and boreholes.