Cardiovascular Complications of HIV-Associated Immune Dysfunction

Prolonged survival in HIV infection is accompanied by an increased frequency of non-HIV-related comorbidities. It is suggested that cardiovascular diseases (CVD) occur earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed which can be categorized into traditional and nontraditional risk factors. Immune dysfunction is a nontraditional risk factor that contributes significantly to cardiovascular pathology. Markers of inflammation are elevated in HIV-infected patients, and elevations in markers such as high-sensitivity C-reactive protein, D-dimer, and interleukin-6 (IL-6) have been associated with increased risk for cardiovascular disease. However, the data currently suggest the most practical advice is to start antiretroviral therapy early and to manage traditional risk factors for CVD aggressively. A better understanding of the mechanisms of CVD in this population and further efforts to modify chronic inflammation remain an important research area

Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation

Significance: Traumatic injury elicits a complex, dynamic, multidimensional inflammatory response that is intertwined with complications such as multiple organ dysfunction and nosocomial infection. The complex interplay between inflammation and physiology in critical illness remains a challenge for translational research, including the extrapolation to human disease from animal models. Recent Advances: Over the past decade, we and others have attempted to decipher the biocomplexity of inflammation in these settings of acute illness, using computational models to improve clinical translation. In silico modeling has been suggested as a computationally based framework for integrating data derived from basic biology experiments as well as preclinical and clinical studies. Critical Issues: Extensive studies in cells, mice, and human blunt trauma patients have led us to suggest (i) that while an adequate level of inflammation is required for healing post-trauma, inflammation can be harmful when it becomes self-sustaining via a damage-associated molecular pattern/Toll-like receptor-driven feed-forward circuit; (ii) that chemokines play a central regulatory role in driving either self-resolving or self-maintaining inflammation that drives the early activation of both classical innate and more recently recognized lymphoid pathways; and (iii) the presence of multiple thresholds and feedback loops, which could significantly affect the propagation of inflammation across multiple body compartments. Future Directions: These insights from data-driven models into the primary drivers and interconnected networks of inflammation have been used to generate mechanistic computational models. Together, these models may be used to gain basic insights as well as serving to help define novel biomarkers and therapeutic targets. Antioxid. Redox Signal. 23, 1370?1387.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140310/1/ars.2015.6398.pd

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Lung injury in myocardial infarction-associated cardiogenic shock supported by venoarterial extracorporeal membrane oxygenation: a scoping review

Abstract Background Acute lung injury and acute respiratory failure are frequent complications of cardiogenic shock and are associated with increased morbidity and mortality. Even with increased use of temporary mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation (VA-ECMO), acute lung injury related to cardiogenic shock continues to have a determinantal effect on patient outcomes. Objectives To summarize potential mechanisms of acute lung injury described in patients with cardiogenic shock supported by VA-ECMO and determine current knowledge gaps. Methods We searched literature from January 1st, 2010, to December 31st, 2023, using MEDLINE, EMBASE, and Web of Science databases on February 27th, 2024. The search strategy was split into two main domains: (a) cardiogenic shock and ECMO and (b) Acute respiratory failure and ECMO. Results The search yielded 2246 citations. After 743 duplicates were removed, 1465 citations remained. Of these studies, 1456 were excluded based on the exclusion criteria, leaving the final eight studies we included in our scoping review. We identified disruption of the pulmonary blood flow in patients with cardiogenic shock, with cardiac arrest being an extreme form of cardiogenic shock. Placing the patient on VA-ECMO could intensify this process of lung injury. Conclusion Acute lung injury in patients with cardiogenic shock, especially when supported by VA ECMO, is a significant complication that is associated with increased morbidity and mortality. There is a limited understanding of the underlying mechanisms that could represent opportunities for future research to mitigate its development and provide the best approach to protecting and monitoring lung function

Can we reduce the risk of neurological injury in critically ill children on initiation of ECLS? A narrative review of potential modifiable factors

Neurological morbidity and mortality remain high in children requiring extracorporeal membrane oxygenation (ECMO). Although the severity of illness at the time of ECMO initiation and the nature of the underlying disease are strongly linked to the development of acute brain injury, several important factors are associated with neurological complications during ECMO support. Many of these factors, particularly those encountered during the early phase of ECMO initiation (first 24 hours), may be modifiable and represent potential targets for interventional studies aiming for improvement of neurological outcomes in pediatric ECMO patients. In this review from the European Extracorporeal Life Support Organization (EuroELSO) Working Group on Neurologic Monitoring and Outcome, we aim to summarize current knowledge on modifiable factors associated with brain injury during ECMO and their potential impact on outcome

Elevated Admission Base Deficit Is Associated with a Complex Dynamic Network of Systemic Inflammation Which Drives Clinical Trajectories in Blunt Trauma Patients

We hypothesized that elevated base deficit (BD) ≥ 4 mEq/L upon admission could be associated with an altered inflammatory response, which in turn may impact differential clinical trajectories. Using clinical and biobank data from 472 blunt trauma survivors, 154 patients were identified after excluding patients who received prehospital IV fluids or had alcohol intoxication. From this subcohort, 84 patients had a BD ≥ 4 mEq/L and 70 patients with BD < 4 mEq/L. Three samples within the first 24 h were obtained from all patients and then daily up to day 7 after injury. Twenty-two cytokines and chemokines were assayed using Luminex™ and were analyzed using two-way ANOVA and dynamic network analysis (DyNA). Multiple mediators of the innate and lymphoid immune responses in the BD ≥ 4 group were elevated differentially upon admission and up to 16 h after injury. DyNA revealed a higher, sustained degree of interconnectivity of the inflammatory response in the BD ≥ 4 patients during the initial 16 h after injury. These results suggest that elevated admission BD is associated with differential immune/inflammatory pathways, which subsequently could predispose patients to follow a complicated clinical course

Level of sedation in patients with COVID-19 supported with ECMO: A comparative analysis of the critical care consortium international database

Background: Liberation from sedation may be beneficial for patients with acute respiratory distress syndrome supported by veno-venous (VV) extracorporeal membrane oxygenation (ECMO). Currently, there is limited evidence to support this approach. Therefore, this study aimed to compare the 90-day patient mortality of different sedation strategies in COVID-19 patients supported with VV ECMO. Methods: Retrospective, observational sub-study of the COVID-19 Critical Care Consortium database including COVID-19 patients supported with VV ECMO. Two cohorts were compared: high sedation patients who received neuromuscular blocking agents (NMBAs) throughout ECMO and low sedation patients who did not receive NMBA consistently. Patients’ level of sedation during ECMO was also considered. The primary outcome was 90-day in-hospital mortality and was assessed using cause-specific Cox proportional hazard models. Results: 224 low and 104 high sedation patients were included. Pre-ECMO respiratory condition prior was similar between groups, except for the ratio of partial pressure of oxygen to inspired fraction of oxygen, which was lower in the high sedation group at 93 [61–130] than the low sedation group at 106 [69–140]. No difference was observed in disease severity scores between cohorts. Low sedation patients had longer ECMO runs, more circuit changes, but lower infectious and hemorrhagic complications. Higher sedation was associated with a hazard ratio for death of 3.23 (95% CI 2.16–4.83) compared to low sedation. Conclusions: Reduced sedation in COVID-19 ECMO patients is feasible and may be associated with improved survival and reduced complications compared to continuous paralysis, albeit with longer ECMO runs.No Full Tex