Search Results (1,165)

Objectives: To compare the health status, exercise capacity, and health-related quality of life (HRQoL) in survivors of COVID-19-associated acute respiratory distress syndrome (ARDS) at 8, 12, and 24 months post-diagnosis. Methods: We conducted a prospective, single-center follow-up study embedded within a larger multicenter cohort of adults with COVID-19 who required hospital admission. Eligible participants underwent clinical interviews, physical examinations, chest radiography, and the 6-min walk test (6MWT). Standardized scales were used to assess post-traumatic stress disorder (PTSD), anxiety, depression, and HRQoL. Results: Out of 1295 patients with COVID-19, 365 developed ARDS, of whom 166 survived. After excluding deaths and loss to follow-up, 95 patients were monitored for 24 months. Over 60% of patients had persistent symptoms, though significant improvements were recorded in quality of life and physical recovery. More than 70% recovered their previous physical capacity, but 15% did not return to their usual lifestyle habits. Symptoms such as arthralgia and fatigue decreased, but cognitive issues, such as memory loss and insomnia, persisted. Radiological improvements were noted, although pulmonary function remained impaired. The prevalence of PTSD and anxiety decreased, while depression remained stable at around 30%. Conclusions: Long COVID continues to impose significant physical, mental, and social challenges. Symptoms like fatigue and anxiety have a profound impact on daily life. Strategies are urgently needed to help patients regain health and resume their normal lives. Full article

Background/Objectives: Regulation of acute inflammatory responses is crucial for host mortality and morbidity induced by pathogens. The pathogenesis of acute respiratory distress syndrome (ARDS) and sepsis are associated with systemic inflammation. p38 MAPK is a crucial regulator of inflammatory responses and is a potential target for acute inflammatory diseases, including ARDS and sepsis. We investigated the therapeutic effects of the TAT-TN13 peptide (TN13) on severe inflammatory diseases, including ARDS and sepsis, in vivo. Methods: To establish the ARDS model, C57BL/6 mice were intranasally (i.n.) administered lipopolysaccharide (LPS; 5 mg/kg, 40 µL) to induce lung inflammation. As a positive control, dexamethasone (DEX; 0.2 mg/kg) was administered intraperitoneally (i.n.) 1 h post-LPS exposure. In the experimental groups, TN13 was administered intranasally (i.n.) at doses of 2.5 mg or 5 mg/kg at the same time point. In the LPS-induced sepsis model, mice received an intraperitoneal injection of LPS (20 mg/kg) to induce systemic inflammation. TN13 (25 mg/kg, i.p.) was administered 1 h after LPS treatment. Control mice received phosphate-buffered saline (PBS). Lung histopathology, inflammatory cell infiltration, cytokine levels, and survival rates were assessed to evaluate TN13 efficacy. Results: TN13 significantly reduced inflammatory cell recruitment and cytokine production in the lungs, thereby mitigating LPS-induced ARDS. In the sepsis model, TN13 treatment improved survival rates by suppressing inflammatory responses. Mechanistically, TN13 exerted its effects by inhibiting the p38 MAPK/NF-κB signaling pathway. Conclusions: These results collectively suggested that TN13 could be an effective treatment option for severe inflammatory diseases. Full article

Burn injuries often lead to severe complications, including acute respiratory distress syndrome (ARDS), driven in part by systemic inflammation and glycocalyx disruption. In this study, we analyzed the sera of 28 patients after burn trauma and utilized single-cell RNA sequencing (scRNA-seq) along with microarray transcriptomic analysis to decipher the impact of burn injury on glycocalyx derangement. We observed the significant upregulation of immune cell-derived degrading enzymes, particularly matrix metalloproteinase-8 (MMP8), which correlated with increased immune cell infiltration and glycocalyx derangement. Serum analyses of burn patients revealed significantly elevated levels of shed glycocalyx components and MMP8, both correlating with the presence of inhalation injury. Consequently, the treatment of human in vitro lung tissue models with MMP8 induced significant glycocalyx shedding in alveolar epithelial cells. Together, based on these findings, we propose that MMP8 plays a previously unrecognized role in glycocalyx disruption and subsequent lung injury post-burn, which implies that inhibiting MMP8 may represent a promising therapeutic strategy for alleviating lung injury after burn trauma. Full article

Veno-venous extracorporeal membrane oxygenation (vvECMO) is a life-saving intervention for severe respiratory failure unresponsive to conventional therapies. However, managing refractory hypoxemia in morbidly obese patients poses significant challenges due to the unique physiological characteristics of this population, including hyperdynamic circulation, elevated cardiac output, and increased oxygen consumption. These factors can limit the effectiveness of vvECMO by diluting arterial oxygen content and complicating oxygen delivery. Refractory hypoxemia in obese patients supported by vvECMO often stems from an imbalance between ECMO blood flow and cardiac output. Hyperdynamic circulation exacerbates the recirculation of oxygenated blood and impairs the efficiency of oxygen transfer. To address these challenges, a stepwise, individualized approach is essential. Strategies to reduce oxygen consumption include deep sedation, neuromuscular blockade, and temperature control. Cardiac output modulation can be achieved through beta-blockers and cautious therapeutic hypothermia. Optimizing oxygen delivery involves improving residual lung function; high positive end-expiratory pressure ventilation guided by esophageal pressure monitoring; prone positioning; and adjustments to the ECMO circuit, such as using dual oxygenators, larger membranes, or additional drainage cannulas. This review highlights the interplay of physiological adaptations and technical innovations required to overcome the challenges of managing refractory hypoxemia in obese patients during vvECMO. By addressing the complexities of high cardiac output and obesity, clinicians can enhance the effectiveness of vvECMO and improve outcomes for this high-risk population. Full article

Acute respiratory distress syndrome (ARDS) is a heterogeneous group of disease entities that are associated with acute hypoxic respiratory failure and significant morbidity and mortality. With a better understanding and phenotyping of lung injury, novel pathophysiologic mechanisms demonstrate the impact of a patient’s excessive spontaneous breathing effort on perpetuating lung injury. Patient self-inflicted lung injury (P-SILI) is a recently identified phenomenon that delves into the impact of spontaneous breathing on respiratory mechanics in patients with lung injury. While the studies are hypothesis-generating and have been demonstrated in animal and human studies, further clinical trials are needed to identify its impact on ARDS management. The purpose of this review article is to highlight the physiologic mechanisms of P-SILI, novel tools and methods to detect P-SILI, and to review the current literature on non-invasive and invasive respiratory management in patients with ARDS. Full article

Genetic variants related to susceptibility to chronic respiratory conditions such as interstitial lung disease (ILD) could share critical pathways in the pathogenesis of COVID-19 and be implicated in COVID-19 outcomes and post-COVID-19. We aimed to identify the participation of genetic variants in lung function and ILD genes in severe COVID-19 outcomes and post-COVID-19 condition. We studied 936 hospitalized patients with COVID-19. The requirement of invasive mechanical ventilation (IMV) and the acute respiratory distress syndrome (ARDS) classification were considered. The mortality was assessed as the in-hospital death. The post-COVID-19 group included 102 patients evaluated for pulmonary function tests four times during the year after discharge. Five variants (FAM13A rs2609255, DSP rs2076295, TOLLIP rs111521887, TERT rs2736100, and THSD4 rs872471) were genotyped using TaqMan assays. A multifactor dimensionality reduction method (MDR) was performed for epistasis estimation. The TERT rs2736100 and THSD4 rs872471 variants were associated with differential risk for ARDS severity (moderate vs. severe, CC + CA, p = 0.044, OR = 0.66, 95% CI = 0.44–0.99; and GG p = 0.034, OR = 2.22, 95% CI = 1.04–4.72, respectively). These variants and FAM13A rs2609255 were also related to pulmonary function post-COVID-19. The MDR analysis showed differential epistasis and correlation of the genetic variants included in this study. The well-known variants in recognized genes related to pulmonary function worsening and interstitial disorders are related to the severity and mortality of COVID-19 and lung performance in the post-COVID-19 condition. Full article

The renal resistive index (RRI), a Doppler ultrasound-derived parameter measuring renal vascular resistance, has emerged as a promising non-invasive tool to evaluate renal hemodynamics in critically ill patients, particularly those with acute respiratory distress syndrome (ARDS) and heart failure (HF). This narrative review examines the current evidence for RRI measurement in these conditions, exploring its physiological bases, methodology, clinical applications, and limitations. In ARDS, RRI reflects the complex interactions between positive pressure ventilation, hypoxemia, and systemic inflammation, showing a role in predicting acute kidney injury and monitoring response to interventions. In HF, RRI is able to assess venous congestion and cardiorenal interactions and can also serve as a prognostic indicator. Many studies have shown RRI’s superiority or complementarity to traditional biomarkers in predicting renal dysfunction, although its interpretation requires consideration of multiple patient-related factors. Key challenges include operator dependency, lack of standardization, and complex interpretation in multi-organ dysfunction. Future research should focus on measurement standardization, development of automated techniques, investigation of novel applications like intraparenchymal renal resistive index variation, and validation of RRI-guided management strategies. Despite its limitations, RRI represents a valuable tool that offers bedside and real-time insights into renal hemodynamics and potential guidance for therapeutic interventions. Further research is needed to fully clarify its clinical potential and address current limitations, particularly in critical care settings involving multiple organ dysfunction. Full article

Cellular nucleosomes—the structural and functional units of chromatin—are inherently present in cells. During cellular damage or cell death, nucleosomes are released into circulation, either actively or passively. Once released, nucleosomes can become immunogenic entities through various mechanisms. The nucleosomal proteins in nucleosomes, called histones, play a pivotal role in inducing immunogenicity. However, intact nucleosomes are more immunogenic than the histones alone, as nucleosomal double-stranded deoxyribonucleic acid (dsDNA) enhances its immunogenic potential. Our recent study has shown that circulating histones are predominantly nucleosomal histones rather than free histones. Consequently, circulating histones primarily function as integral parts of circulating nucleosomes rather than acting independently. Circulating nucleosomes and their associated histones are implicated in the pathogenesis of a wide array of diseases. Notably, they are critical in the pathogenesis of lung injury and sepsis. These diseases have high morbidity and mortality rates and lack early diagnostic biomarkers. Further investigation is required to fully elucidate the role of circulating nucleosomes and their associated histones in disease processes. This review aims to discuss the current understanding of circulating nucleosomes and histones in the pathogenesis of lung injury and sepsis, with a focus on the underlying mechanisms. Full article

Background/Objectives: Corona virus disease 2019 (COVID-19) poses a threat to global public health. The early identification of critical cases is crucial to providing timely treatment to patients. Here, we investigated whether the neutrophil levels could predict COVID-19 complications. Methods: We performed a retrospective study of patients with COVID-19, admitted to the Cheikh Khalifa International University Hospital, Casablanca, Morocco. Laboratory test results collected upon admission and during hospitalization were analyzed based on clinical information. Results: Our study revealed that a rise in neutrophil “PNN” levels was associated with respiratory deterioration and intubation. They were positively correlated with the procalcitonin and C-reactive protein levels. Interestingly, PNN (polynuclear neutrophil) levels on day 5 proved to be a better predictor of intubation, acute respiratory distress syndrome (ARDS), and mortality than the initial PNN counts, C-reactive protein, or procalcitonin. Moreover, binary logistic regression with stratified PNN-day 5 data revealed that a PNN level on day 5 > 7.7 (109/L) was an independent risk factor for mortality and ARDS. Finally, the PNN levels on day 5 and proinflammatory cytokine IL-6 were positively correlated. Conclusions: Our data showed that neutrophilia proved to be an excellent predictor of complications and mortality during hospitalization and could be used to improve the management of patients with COVID-19. Full article

COVID-19, first identified in December 2019 in Wuhan, China, is caused by the SARS-CoV-2 virus, a pathogen that primarily targets the respiratory system and can lead to severe conditions such as acute respiratory distress syndrome (ARDS). Among the seven coronaviruses known to infect humans, three—SARS-CoV, MERS-CoV, and SARS-CoV-2—are associated with severe illness and significant morbidity. SARS-CoV-2 is an enveloped, single-stranded RNA virus that utilizes the angiotensin-converting enzyme 2 (ACE2) receptor for cellular entry. The genetic sequence of SARS-CoV-2 is highly mutable, leading to the emergence of variants that alter disease pathology and transmission dynamics. The World Health Organization (WHO) has classified these mutations into variants of concern (VOCs), variants of interest (VOIs), and variants under monitoring (VUMs). This review provides an in-depth analysis of both historical and emerging SARS-CoV-2 variants, summarizes recent advancements in diagnostic methods for SARS-CoV-2 detection, and discusses current therapeutic strategies for COVID-19, with a particular focus on virus-like particle (VLP) vaccines developed in recent years. Additionally, we highlight ongoing therapeutic approaches and their implications for managing COVID-19. Full article

Background: Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose: We aimed to identify the common clinical phenotypes of AF patients and compare clinical outcomes between these subgroups. Methods: A 1% representative sample of all AF patients hospitalized between 2010 and 2019 was identified from the French national database. Agglomerative hierarchical cluster analysis was performed using Ward’s method and squared Euclidian distance to derive the clusters of patients. Cox regression analyses were used to evaluate outcomes including all-cause death, cardiovascular death, non-cardiovascular death, ischemic stroke, hospitalization for heart failure (HF) and composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest (VT/VF/CA) over a mean follow-up period of 2.0 ± 2.3 years. Results: Four clusters were generated from the 12,688 patients included. Cluster 1 (n = 2375) was younger, low cardiovascular disease (CVD)-risk group with a high cancer prevalence. Clusters 2 (n = 6441) and 3 (n = 1639) depicted moderate-risk groups for CVD. Cluster 3 also had the highest degree of frailty and lung disease while Cluster 4 (n = 2233) represented a high-risk cohort for CVD. After adjusting for confounders, with cluster 1 as the reference, cluster 3 had the highest risk of all-cause death, HR 1.24 (1.09–1.41), ARD (10.3%), cardiovascular death, HR 1.56 (1.19–2.06), ARD (3.3%), non-cardiovascular death, HR 1.20 (1.04–1.38), ARD (6.9%), hospitalization for HF, HR 2.07 (1.71–2.50), ARD (9.1%) and VT/VF/CA, HR 1.74 (1.20–2.53), (ARD 1.3%). Conclusions: Four distinct clusters of AF patients were identified, discriminated by the differential presence of comorbidities. Our findings suggest that hospitalized AF patients with moderate CVD risk may have a poorer prognosis compared to hospitalized AF patients with high CVD risk in the presence of lung pathology and frailty. This subgroup of patients may require more stringent management of existing comorbidities such as chronic obstructive pulmonary disease and sleep apnea, alongside their AF. Full article

Sepsis is a systemic inflammatory response syndrome of suspected or confirmed infectious origin, which frequently culminates in multiorgan failure, including cardiac involvement. Septic cardiomyopathy (SCM) remains a poorly defined clinical entity, lacking a formal or consensus definition and representing a significant knowledge gap in critical care medicine. It is an often-underdiagnosed complication of sepsis. The only widely accepted aspect of its definition is that SCM is a transient myocardial dysfunction occurring in patients with sepsis, which cannot be attributed to ischemia or pre-existing cardiac disease. The pathogenesis of SCM appears to be multifactorial, involving inflammatory cytokines, overproduction of nitric oxide, mitochondrial dysfunction, calcium homeostasis dysregulation, autonomic imbalance, and myocardial edema. Diagnosis primarily relies on echocardiography, with advanced tools such as tissue Doppler imaging (TDI) and global longitudinal strain (GLS) providing greater sensitivity for detecting subclinical dysfunction and guiding therapeutic decisions. Traditional echocardiographic findings, such as left ventricular ejection fraction measured by 2D echocardiography, often reflect systemic vasoplegia rather than intrinsic myocardial dysfunction, complicating accurate diagnosis. Right ventricular (RV) dysfunction, identified as a critical component of SCM in many studies, has multifactorial pathophysiology. Factors including septic cardiomyopathy itself, mechanical ventilation, hypoxemia, and hypercapnia—particularly in cases complicated by acute respiratory distress syndrome (ARDS)—increase RV afterload and exacerbate RV dysfunction. The prognostic value of cardiac biomarkers, such as troponins and natriuretic peptides, remains uncertain, as these markers primarily reflect illness severity rather than being specific to SCM. Treatment focuses on the early recognition of sepsis, hemodynamic optimization, and etiological interventions, as no targeted therapies currently exist. Emerging therapies, such as levosimendan and VA-ECMO, show potential in severe SCM cases, though further validation is needed. The lack of standardized diagnostic criteria, combined with the heterogeneity of sepsis presentations, poses significant challenges to the effective management of SCM. Future research should focus on developing cluster-based classification systems for septic shock patients by integrating biomarkers, echocardiographic findings, and clinical parameters. These advancements could clarify the underlying pathophysiology and enable tailored therapeutic strategies to improve outcomes for SCM patients. Full article

Background: Patients undergoing prolonged mechanical ventilation commonly require tracheotomy. The main aim of this study was to evaluate the outcomes of tracheotomy for patients with acute respiratory distress syndrome (ARDS) associated with COVID-19 in low-resource settings. Methods: A retrospective, single-center, observational cohort study was performed on patients with ARDS associated with COVID-19. Patients who underwent intubation alone were compared with those who received both intubation and subsequent tracheotomy. The analysis included patient demographics, comorbidities, and outcomes. Results: Patients undergoing tracheotomy (n = 89) were compared with intubated patients (n = 622). The median time from intubation to tracheotomy was 10 days (IQR: 6–15 days). Overall, 608 patients (85.5%) died in the hospital. Thirty-seven patients (35.9%) in the survival group had tracheostomy compared with fifty-two patients (8.5%) in the non-survival group (p < 0.001). The Kaplan–Meier curve shows a higher probability of survival in the tracheotomy group compared with the non-tracheotomy group (log-rank test: p < 0.001). Tracheotomy was found to be independently associated with lower in-hospital mortality (HR = 0.16 [95% CI: 0.11–0.23], p < 0.001) in the multivariable Cox proportional hazards regression analysis after adjusting for potential confounding factors. Furthermore, tracheotomy was associated with a higher cumulative incidence of being alive and off the ventilator at day 28 (SHR = 2.87 [95% CI: 1.88–4.38], p < 0.001). Conclusions: Tracheotomy was associated with reduced in-hospital mortality and longer ventilator-free days. Full article

Medical instruments are essential in pediatric intensive care units (PICUs) for measuring respiratory parameters to prevent health complications. However, the assessment of acute respiratory distress (ARD) is still conducted through intermittent visual examination. This process is subjective, labor-intensive, and prone to human error, making it unsuitable for continuous monitoring and early detection of deterioration. Previous studies have proposed solutions to address these challenges, but their techniques rely on color information, the performance of which can be influenced by variations in skin tone and lighting conditions. We propose leveraging multi-modality data to address these limitations. Our method integrates color and depth data using deep convolutional neural networks with a late feature fusion scheme. We train and evaluate our model on a dataset of 153 patients with respiratory illnesses, 86 of whom have ARD of varying severity levels. Experimental results demonstrate that multi-modality data combined with simple late fusion techniques are more effective with limited data, offering higher confidence scores compared to using color information alone. Our approach achieves an accuracy of 85.2%, a precision of 86.7%, a recall of 85.2%, and an $F_1$ score of 85.8%. These findings suggest that multi-modality data provide a promising solution for improving ARD detection accuracy and confidence in clinical settings. Full article

It is known that the presence of redox-inactive metals in the active center of an enzyme has a significant effect on its activity. In this regard and for other reasons, the effect of redox-inactive metals on redox processes, such as electron transfer, oxygen and hydrogen atom transfer, as well as the breaking and formation of O–O bonds in reactions catalyzed by transition metals, has been widely studied. Many questions about the role of redox-inactive metals in the mechanisms of these reactions remain open. In this paper, the mechanism of catalysis by bi- and triple hetero-binuclear heteroligand complexes including Ni and redox-inactive alkali metals ((A) {Ni(acac)₂∙L²} and (B) {Ni(acac)₂∙L²∙PhOH} (L² = MSt (M = Li, Na, or K)) in the process of the selective oxidation of ethylbenzene by molecular oxygen into α-phenyl ethyl hydroperoxide is considered. The activity of A and B complexes towards O₂, ROOH, and RO₂^• radicals was studied. Based on kinetic data, we suggest that the high catalytic efficiency of B triple complexes in oxidation processes may be associated with the role of outer-sphere regulatory interactions, with the formation of stable supramolecular structures due to intermolecular H bonds. This assumption was confirmed using the AFM method. Prospects for studying catalysis by complexes ({Ni(acac)₂∙L²} and {Ni(acac)₂∙L²∙PhOH}) that are models of NiARD (Ni-Acyreductone dioxygenase) are discussed. Full article