Heart-lung crosstalk in acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) is initiated by a primary insult that triggers a cascade of pathological events, including damage to lung epithelial and endothelial cells, extracellular matrix disruption, activation of immune cells, and the release of pro-inflammatory mediators. These events lead to increased alveolar-capillary barrier permeability, resulting in interstitial/alveolar edema, collapse, and subsequent hypoxia and hypercapnia. ARDS not only affects the lungs but also significantly impacts the cardiovascular system. We conducted a comprehensive literature review on heart-lung crosstalk in ARDS, focusing on the pathophysiology, effects of mechanical ventilation, hypoxemia, and hypercapnia on cardiac function, as well as ARDS secondary to cardiac arrest and cardiac surgery. Mechanical ventilation, essential for ARDS management, can increase intrathoracic pressure, decrease venous return and right ventricle preload. Moreover, acidemia and elevations in transpulmonary pressures with mechanical ventilation both increase pulmonary vascular resistance and right ventricle afterload. Cardiac dysfunction can exacerbate pulmonary edema and impair gas exchange, creating a vicious cycle, which hinders both heart and lung therapy. In conclusion, understanding the heart-lung crosstalk in ARDS is important to optimize therapeutic strategies. Future research should focus on elucidating the precise mechanisms underlying this interplay and developing targeted interventions that address both organs simultaneously.

Risk Factors and Outcomes Associated with Pneumothorax in Very Preterm Infants.

BACKGROUND/OBJECTIVES: Pneumothorax can be a major complication of neonatal lung diseases. We aim to delineate trends and describe the main outcomes related to pneumothorax in very preterm infants (VPI). METHODS: Preterm infants < 32 weeks of gestation admitted in two-level III neonatal intensive care units (1995-2019) were included. Risk factors and outcomes were assessed by logistic regression and adjusted for gestational age (GA). RESULTS: In total, 4271 VPI with a mean GA of 28.7 ± 2.3 weeks were evaluated. Pneumothorax was diagnosed in 174 patients (4.1%, 95% Confidence Interval (CI) 3.5-4.7) with its incidence inversely proportional to GA: 9.9% in 23-25 w and 2.1% in 30-31 w (p < 0.001), but stable over the years 1995-1999 (5.2%) and 2015-2019 (4.2%) (p = 0.309). Patients with pneumothorax exhibited higher rates of severe intraventricular hemorrhage (IVH) (Odds Ratio (OR) = 2.0 (95%CI 1.3-3.1), p = 0.003), bronchopulmonary dysplasia (OR = 2.7 (95%CI 1.7-4.4), p < 0.001), and death (OR = 8.5 (95%CI 6.2-11.6), p < 0.001). Independent risk factors for pneumothorax were GA, prolonged premature rupture of membranes, and intubation in the delivery room. The composite outcome of death or severe IVH was higher in patients with pneumothorax with an adjusted OR = 6.7 (95%CI 4.7-9.6), p < 0.001. Although VPI mortality has significantly decreased over the years (20.3% 1995-1999 and 11.7% 2015-2019, p < 0.001), we found no significant difference in pneumothorax-related deaths. CONCLUSION: Pneumothorax remains a serious threat to VPI, leading to a higher incidence of morbidity, and mortality attributable to this complication has not decreased. Preventive strategies and early recognition are essential for improving disability-free survival in VPI.

Effect of different CPAP levels on ultrasound-assessed lung aeration and gas exchange in neonates.

BACKGROUND: Respiratory distress syndrome (RDS) and transient tachypnoea (TTN) are the two commonest neonatal respiratory disorders. The optimal continuous positive airway pressure (CPAP) to treat them is unknown. We aim to clarify the effect of different CPAP levels on lung aeration and gas exchange in patients with RDS and TTN. METHODS: Prospective, observational, pragmatic, physiological cohort study. CPAP was sequentially increased from 4 to 6 and 8 cmH2O and backwards, with interposed wash-out periods. Lung aeration was assessed with a validated neonatal lung ultrasound score. Gas exchange was non-invasively evaluated with transcutaneous monitoring. Ultrasound score and PtcO2/FiO2 ratio were the co-primary outcomes. PtcCO2 and other oxygenation metrics were the secondary outcomes. RESULTS: 30 neonates with RDS and 30 with TTN were studied. Each CPAP increment significantly (overall always p < 0.001) improved both lung aeration and oxygenation, but the increase from 6 to 8 cmH2O achieved a small absolute benefit. In RDS patients, the absolute improvements were small and the diagnosis of TTN was significantly associated with greater improvement of lung aeration (ß= -1.4 (95%CI: -2.4; -0.3), p = 0.01) and oxygenation (ß = 39.6 (95%CI: 4.1; 75.1), p = 0.029). Aeration improved in 16 (53.3%) and 27 (90%) patients in the RDS and TTN groups, respectively (p = 0.034). Lung aeration showed significant hysteresis in TTN patients. Secondary outcomes gave similar results. CONCLUSIONS: Increasing CPAP from 4 to 8 cmH2O improves ultrasound-assessed lung aeration and oxygenation in RDS and TTN. The absolute improvements are small when CPAP is beyond 6 cmH2O or for RDS patients.

ASXL1-related Bohring-Optiz syndrome complicated by persistent neonatal pulmonary hypertension and abnormal alveoli formation.

Bohring-Opitz syndrome (BOS) is a rare disease with a characteristic facial appearance and limb position. This report describes a case of BOS complicated by persistent pulmonary hypertension of the newborn (PPHN) and formation of abnormal alveoli that was confirmed by autopsy. A female neonate was born by cesarean section at 37 weeks and 2 days of gestation and found to have a nevus flammeus, exophthalmos, abnormal palate, retraction of the mandible, and a posture characteristic of BOS. The patients had severe PPHN requiring inhalation of nitric oxide. Genetic testing revealed a de novo frameshift variant in ASXL1. Autopsy revealed that the lung was at the saccular stage, equivalent to 28-34 weeks of gestation. This is the first report to present pathological evidence of immaturity of the lung that may be associated with PPHN in a patient with BOS caused by a variant in ASXL1.

Current Trends in the Imaging Diagnosis of Neonatal Respiratory Distress Syndrome (NRDS): Chest X-ray Versus Lung Ultrasound.

Neonatal respiratory distress syndrome (NRDS) is a major cause of morbidity and mortality in newborns, particularly in neonatal intensive care units (NICUs). Until recently, its diagnosis had been based on clinical signs, arterial blood gas analysis, and chest X-ray (CXR). However, the frequent use of CXR exposes newborns to ionizing radiation, which can have long-term negative effects, including an increased risk of cancer, especially among premature infants. Lung ultrasound (LUS) has been proposed as a promising alternative for diagnosing NRDS due to its many advantages: no exposure to radiation, the ability to be performed at the bedside, repeatability, and ease of use. This review compared the diagnostic accuracy of LUS with the reference standard, CXR, in evaluating NRDS in newborns admitted to the NICU. Studies have shown that LUS can identify specific signs of NRDS, such as bilateral "white lung," pleural line abnormalities, and lung consolidations. The method has high sensitivity and specificity for diagnosing this condition and offers several advantages over other diagnostic methods; it does not involve ionizing radiation, thereby eliminating the risk of radiation exposure; it is cost-effective, easy to use, and can be performed at the patient's bedside, making it a viable alternative to CXR for reducing ionizing radiation exposure. Additionally, LUS can be used to monitor the progression of respiratory diseases and guide clinical management, especially in determining the optimal timing for surfactant administration in newborns with respiratory distress syndrome (RDS). We conclude that LUS is an effective and non-invasive alternative method for diagnosing and managing NRDS, with the potential to improve the safety and quality of care in the NICU, where rapid and safe diagnostic tools are essential for managing the health of newborns.

Environmental Risk Factors for Acute Respiratory Distress Syndrome.

Several environmental exposures increase susceptibility to the acute respiratory distress syndrome (ARDS). Specifically, chronic exposure to ambient air pollution, cigarette smoke, and alcohol "prime" the lung via epithelial injury, endothelial dysfunction, and immunomodulatory mechanisms, increasing the risk and severity of ARDS following an array of acute insults. Future research of these pathways may reveal therapeutic targets. Relevant emerging threats, such as electronic cigarettes and vaping, wildfire smoke, and the environmental hazards associated with climate change, may also be associated with ARDS. Building upon existing public policy interventions can prevent substantial morbidity and mortality from ARDS.

Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome.

BACKGROUND: Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a "head-to-head" comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic "signature". METHOD: This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs)  would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects. RESULTS: When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19. CONCLUSION: Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.

Adherence to Lung Protective Ventilation in ARDS: A Mixed Methods Study Using Real-Time Continuously Monitored Ventilation Data.

BACKGROUND: Lung-protective ventilation is a standard intervention for mitigating ventilator-induced lung injury in patients with ARDS. Despite its efficacy, adherence to contemporary evidence-based guidelines remains suboptimal. We aimed to identify factors that affect the adherence of staff to applying lung-protective ventilation guidelines by analyzing real-time, continuously monitored ventilation data over a 5-year longitudinal period. METHODS: We conducted retrospective cohort and qualitative studies. Subjects with billing code J80 who survived at least 48 h of continuous mandatory ventilation with volume control in critical care settings between January 1, 2018, and December 31, 2022, were eligible. Tidal volume was measured dynamically (1-min resolution) and averaged hourly. The lung-protective ventilation setting studied was ≤ 6 mL/kg predicted body weight. A subgroup analysis was conducted by considering COVID-19 status. Focus groups of critical-care providers were convened to investigate the possible reasons for the non-utilization of lung-protective ventilation. RESULTS: Among 1,055 subjects, 42.4% were on lung-protective ventilation settings at 48 h. Male sex was correlated with lung-protective ventilation (odds ratio [OR] 1.63, 95% CI 1.08-2.47), whereas age ≥ 60 y was associated with no lung-protective ventilation use (OR 0.61, 95% CI 0.39-0.94] in the subjects with non-COVID-19 etiologies. Improved staff adherence was observed in the subjects with COVID-19 early in the pandemic when COVID-19 (OR 1.48, 95% CI 1.07-2.04), male sex (OR 2.42, 95% CI 1.79-3.29), and neuromuscular blocking agent use within 48 h (OR 1.69, 95% CI 1.25-2.29) were correlated with staff placing subjects on lung-protective ventilation. However, lung-protective ventilation use occurred less frequently by staff managing subjects with cancer (OR 0.59, 95% CI 0.35-0.99) and hypertension (OR 0.62, 95% CI 0.45-0.85). Focus groups supported these findings and highlighted the need for an accurate height measurement on unit admission to determine the appropriate target tidal volume. CONCLUSIONS: Staff are not yet universally adherent to lung-protective ventilation best practices. Strategies, for example, continuous monitoring, with frequent feedback to clinical teams may help.

Important functions and molecular mechanisms of aquaporins family on respiratory diseases: potential translational values.

Aquaporins (AQPs) are a subgroup of small transmembrane transporters that are distributed in various types of tissues, including the lung, kidney, heart and central nervous system. It is evident that respiratory diseases represent a significant global health concern, with a considerable number of deaths occurring worldwide. Recent researches have demonstrated that AQPs play a pivotal role in respiratory diseases, including chronic obstructive pulmonary disease (COPD), asthma, acute respiratory distress syndrome (ARDS), and particularly non-small cell lung cancer (NSCLC). In the context of NSCLC, the overexpression of AQP1, AQP3, AQP4, and AQP5 has been demonstrated to facilitate tumor angiogenesis, as well as the proliferation, migration, and invasiveness of tumor cells. This review concisely explores the role of AQP family on respiratory diseases, to assess their clinical and translational significance for understanding molecular pathogenesis. However, the potential translation of AQPs biomarkers into clinical applications is promising and the understanding of the precise mechanisms influencing respiratory diseases is still ongoing. Addressing the challenges and outlining the future perspectives in AQPs development is essential for clinical progress in a concise manner.

Efficacy and safety of mesenchymal stem cell therapy for acute respiratory distress syndrome-a systematic review and meta-analysis.

Background: Mesenchymal stem cells (MSC) therapy for acute respiratory distress syndrome (ARDS) represents a burgeoning treatment approach, supported by numerous preclinical studies confirming its efficacy. Our study aims to provide a comprehensive evaluation of both the safety and effectiveness of MSC. Methods: We conducted searches across three databases (PubMed, Embase, Cochrane) for randomized controlled studies up to June 23, 2024. A meta-analysis was performed on variables including adverse events, mortality, changes in the PaO2/FiO2 ratio, intensive care unit (ICU), length of stay, ventilation-free days, and changes in pro-inflammatory and anti-inflammatory cytokines. Relative risk (RR) values were employed for dichotomous variables, while mean difference (MD) and standard mean difference (SMD) were used for continuous variables. Risk bias was assessed using risk of bias 2 (ROB2). Results: The meta-analysis encompassed 17 experiments involving 796 patients, with 410 undergoing MSC treatment and 386 in the control group. Primary outcomes indicated that MSC treatment did not escalate adverse events [RR =1.04; 95% confidence interval (CI): 0.90, 1.19; P=0.59; I2=0%]. On the contrary, it significantly diminishes the mortality (RR =0.79; 95% CI: 0.64, 0.97; P=0.02; I2=0%). Regarding secondary outcomes, MSCs led to a significant improvement in the PaO2/FiO2 ratio for ARDS patients (SMD =0.53; 95% CI: 0.15, 0.92; P=0.007; I2=0%). However, there were no significant differences in ICU length of stay (MD =-1.77; 95% CI: -6.97, 3.43; P=0.50; I2=63%) and ventilation-free days (MD =-1.29; 95% CI: -4.09, 1.51; P=0.37; I2=0%). MSCs significantly lowered C-reactive protein (CRP) (SMD =-0.65; 95% CI: -1.18, -0.13; P=0.01; I2=56%) and interleukin-6 (IL-6) levels compared to the control group (SMD =-0.76; 95% CI: -1.34, -0.17; P=0.01; I2=74%). However, changes in interleukin-10 (AIL-10) (SMD =-0.46; 95% CI: -1.51, 0.58; P=0.38; I2=77%), and changes in tumor necrosis factor-alpha (ATNF-α) (SMD =-1.5; 95% CI: -3.39, 0.40; P=0.12; I2=92%) levels showed no significant changes. Conclusions: MSC therapy demonstrates reliable safety, with a significant impact on reducing mortality and improving certain clinical symptoms. Moreover, in certain aspects, it may alleviate the inflammatory response in ARDS. Nonetheless, these findings necessitate validation through additional high-quality randomized controlled trials.

Resolution of Acute Respiratory Distress Syndrome-Induced Takotsubo Cardiomyopathy with Venovenous Extracorporeal Membrane Oxygenation.

INTRODUCTION: Takotsubo cardiomyopathy (TTCM) can occur in acute respiratory distress syndrome (ARDS) and a few cases in literature were reported to be associated with hemodynamic instability. All these patients were managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO).Case presentation: We present two patients with ARDS-induced TTCM who were managed successfully with venovenous ECMO (VV-ECMO). CONCLUSION: Ventricular function in both patients fully recovered three days after ECMO initiation, and they were subsequently weaned from ECMO once pulmonary function improved.

Antenatal corticosteroids for late small-for-gestational-age fetuses.

OBJECTIVES: To compare neonatal morbidity in late preterm pregnancies with small-for-gestational-age fetuses, between those exposed and not exposed to antenatal corticosteroids (ACS). METHODS: A retrospective study which included growth-restricted fetuses delivered at gestational week 34+0 to 36+6 weeks at a tertiary university-affiliated hospital, from March 2016 to March 2022. The primary composite outcome included the need for oxygen therapy or ventilation, respiratory distress syndrome, transient tachypnea of the newborn, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage grade III/IV and neonatal mortality. RESULTS: The primary composite outcome was comparable between those who did and did not receive ACS (26.1 vs. 20.8 %, p=0.512). Neonatal morbidity rates did not differ significantly between the groups, except for hypoglycemia, which was more common among neonates from ACS-exposed mothers (37.0 vs. 19.5 %, p=0.037). Multivariate analysis, adjusted for gestational diabetes and the mode of delivery showed no significant difference in the composite outcome between the groups (OR=2.03, 95 % CI 0.79-5.20, p=0.142). Cesarean delivery was associated with a higher risk of the primary outcome (OR=2.13, 95 % CI 1.17-3.85, p=0.013). After excluding those who did not receive the initial betamethasone dose within 2-7 days before delivery, the primary composite outcome remained similar between the groups. The primary composite outcome was similar among severely growth-restricted fetuses (<5th percentile) exposed and not exposed to ACS (29.2 vs. 22.0 %, p=0.560). CONCLUSIONS: Among preterm pregnancies complicated by small-for-gestational-age fetuses, ACS did not lower the rate of neonatal morbidity.

Primary mediastinal choriocarcinoma in a woman treated with VIP therapy instead of BEP therapy for the prevention of postoperative acute respiratory distress syndrome.

Primary mediastinal germ cell tumor (PMGCT) is an extragonadal germ cell tumor (GCT) that is classified as a poor-prognosis subtype among GCTs. Among them, choriocarcinoma accounts for 2% and its prognosis is considered to be notably poor. The standard treatment for advanced germ cell tumors is BEP therapy (bleomycin, etoposide, cisplatin), followed by surgical resection. However, treatments containing bleomycin are associated with postoperative acute respiratory distress syndrome (ARDS). We report a 38-year-old woman with locally advanced primary mediastinal choriocarcinoma. A computed tomography (CT) of the chest showed a 6.5 cm solid mass in the anterior mediastinum that had invaded the superior vena cava. Laboratory data revealed a serum total human chorionic gonadotropin (hCG) value of 298,220 mIU/mL. After one course of BEP therapy, her total hCG level decreased markedly, and the patient was switched to VIP therapy (etoposide, ifosfamide, cisplatin), a bleomycin-free regimen, to reduce the risk of ARDS. Three courses of VIP therapy and one course of salvage therapy enabled a complete surgical resection without any complications including ARDS. The patient has been disease-free for 16 months since the resection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00708-z.

Management of severe acute respiratory distress syndrome in Australia and New Zealand (SAGE-ANZ): An observational study.

Objective: Acute respiratory distress syndrome (ARDS) is associated with significant mortality, morbidity, and cost. We aimed to describe characteristics and management of adult patients admitted to intensive care units (ICUs) in Australia and New Zealand with moderate-severe ARDS, to better understand contemporary practice. Design: Bi-national, prospective, observational, multi-centre study. Setting: 19 ICUs in Australia and New Zealand. Participants: Mechanically ventilated patients with moderate-severe ARDS. Main outcome measures: Baseline demographic characteristics, ventilation characteristics, use of adjunctive support therapy and all-cause mortality to day 28. Data were summarised using descriptive statistics. Results: 200 participants were enrolled, mean (±SD) age 55.5 (±15.9) years, 40% (n = 80) female. Around half (51.5%) had no baseline comorbidities and 45 (31%) tested positive for COVID-19. On day 1, mean SOFA score was 9 ± 3; median (IQR) PaO2/FiO2 ratio 119 (89, 142), median (IQR) FiO2 70% (50%, 99%) and mean (±SD) positive end expiratory pressure (PEEP) 11 (±3) cmH2O. On day one, 10.5% (n = 21) received lung protective ventilation (LPV) (tidal volume ≤6.5 mL/kg predicted body weight and plateau pressure or peak pressure ≤30 cm H2O). Adjunctive therapies were received by 86% (n = 172) of patients at some stage from enrolment to day 28. Systemic steroids were most used (n = 127) followed by neuromuscular blockers (n = 122) and prone positioning (n = 27). Median ventilator-free days (IQR) to day 28 was 5 (0, 20). In-hospital mortality, censored at day 28, was 30.5% (n = 61). Conclusions: In Australia and New Zealand, compliance with evidence-based practices including LPV and prone positioning was low in this cohort. Therapies with proven benefit in the treatment of patients with moderate-severe ARDS, such as lung protective ventilation and prone positioning, were not routinely employed.

Anti MDA-5 associated rapidly progressive interstitial lung disease complicated by viral pneumonia - a fatal outcome.

Dermatomyositis is a heterogeneous systemic disease, with 7% to 10% of the individuals presenting the Anti MDA-5 antibody. This subset of patients has clinically amyotropic dermatomyositis, presenting with cutaneous ulcer and rapidly progressive interstitial lung disease. We report the case of a 22-year-old male with a six-month history of low-grade fever associated with myalgia, polyarthralgia, and marked weight loss. He had a history of shortness of breath and high-grade fever 15 days before admission. His clinical features and imaging workup were consistent with acute respiratory distress syndrome. A nasal swab was positive for H1N1 influenza virus infection. During the disease investigation, he succumbed after nine days of admission. The autopsy examination showed diffuse alveolar damage on a background of non-specific interstitial pattern of injury in the lungs. His postmortem muscle biopsy revealed subtle changes of inflammatory myopathy. The brain showed diffuse subarachnoid hemorrhage. Evaluation of postmortem serum sample revealed positivity for Anti MDA-5 and Ro-52 antibodies. This was a case of Anti MDA-5 and Ro-52 associated dermatomyositis with non-specific interstitial pneumonia pattern of lung injury complicated with H1N1 influenza pneumonia, leading to diffuse alveolar damage and subsequent respiratory failure and death. Serum Anti MDA-5 antibodies represent an important biomarker for diagnosing and predicting prognosis for patients with idiopathic inflammatory myopathies, especially clinically amyopathic dermatomyositis. Anti-Ro-52 has been reported in a wide variety of autoimmune diseases, particularly in myositis, scleroderma, and autoimmune liver diseases. Ro-52 autoantibodies are associated with interstitial lung disease (ILD), and their presence should encourage the clinician's curiosity to search for ILD.

Macrophages modulate skeletal muscle wasting and recovery in acute lung injury in mice.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model. We performed flow cytometry of hindlimb muscle to identify myeloid cells pre-injury and time points up to 29 days after intratracheal lipopolysaccharide ALI. We evaluated muscle force and morphometrics after systemic and intramuscular clodronate-induced macrophage depletions between peak lung injury and recovery (day 5-6) versus vehicle control. Our results show muscle leukocytes changed over ALI course with day 3 neutrophil infiltration (130.5 ± 95.6cells/mg control to 236.3 ± 70.6cells/mg day 3) and increased day 10 monocyte abundance (5.0 ± 3.4%CD45+CD11b+ day 3 to 14.0 ± 2.6%CD45+CD11b+ day 10, p = 0.005). Although macrophage count did not significantly change, pro-inflammatory (27.0 ± 7.2% day 3 to 7.2 ± 3.8% day 10, p = 0.02) and anti-inflammatory (30.5 ± 11.1% day 3 to 52.7 ± 9.7% day 10, p = 0.09) surface marker expression changed over the course of ALI. Macrophage depletion following peak lung injury increased muscle mass and force generation. These data suggest muscle macrophages beyond peak lung injury limit or delay muscle recovery. Targeting macrophages could augment muscle recovery following lung injury.

Predictors of CPAP failure after less-invasive surfactant administration in preterm infants.

Introduction: Less-invasive surfactant administration (LISA) is associated with better respiratory outcomes in preterm infants with respiratory distress syndrome. However, mechanical ventilation (MV) shortly after the LISA procedure has been related to lower survival. This study aimed to analyze the trends and main predictors of continuous positive airway pressure (CPAP) failure after LISA. Material and methods: Preterm infants born between 230 and 336 weeks gestational age (GA) in two level III neonatal units who received surfactant were included (2017-2022). Demographic data, lung ultrasound (LUS) scores, the saturation/fraction of inspired oxygen (SF) ratio, technique, time to surfactant administration, and the main neonatal outcomes were collected. Results: Over the study period, 289 inborn preterm infants received surfactant, 174 with the LISA method (60.2%). Patients who received surfactant after intubation in the delivery room (n = 56) were more immature and exhibited worse outcomes. Patients who received surfactant via an endotracheal tube in the neonatal intensive care unit (n = 59) had higher LUS scores and a lower SF ratio than those treated with LISA. The LISA method was associated with less death or bronchopulmonary dysplasia (BPD), with an adjusted odds ratio (aOR) = 0.37 [95% confidence interval (CI), 0.18-0.74, p = 0.006]. CPAP failure after LISA (defined as the need for intubation and MV in the first 72 h of life) occurred in 38 patients (21.8%), inversely proportional to GA (38.7% at 23-26 weeks, 26.3% at 27-30 weeks, and 7.9% at 30-33 weeks (p < 0.001). CPAP failure after LISA was significantly related to death, with an aOR = 12.0 (95% CI, 3.0-47.8, p < 0.001), and moderate to severe BPD, with an aOR = 2.9 (95% CI, 1.1-8.0, p = 0.035), when adjusting for GA. The best predictors of CPAP failure after LISA were GA, intrauterine growth restriction, temperature at admission, the SF ratio, and the LUS score, with a Nagelkerke's R 2 = 0.458 (p < 0.001). The predictive model showed an area under the curve = 0.84 (95% CI, 0.75-0.93, p < 0.001). Conclusions: CPAP failure after LISA is still common in extremely preterm infants, leading to an increase in death or disability. Clinicians must acknowledge the main risk factors of CPAP failure to choose wisely the right patient and the best technique. LUS and the SF ratio at admission can be useful when making these decisions.

Acute respiratory distress syndrome in patients with hematological malignancies: a one-year retrospective nationwide cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. Mortality rate remains high but improvement has been described over the past several years. We aimed to describe characteristics and outcomes of ARDS in HM patients admitted in French ICUs (Intensive Care Units) during a one year-period. Data for this nationwide cohort study were collected from the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)). All patients (18 years or older) admitted to French ICUs in 2017 and with a diagnosis of ARDS were included. Three groups were compared according to the presence of an HM, a solid cancer or no cancer. The primary endpoint was 90-day mortality. Secondary endpoints were the description of ICU management, etiologies of ARDS and mortality risk factors. RESULTS: A total of 12 846 patients with ARDS were included. Among them, 990 had HM and 2744 had a solid cancer. The main malignancies were non-Hodgkin lymphoma (NHL) (28.5%), acute myeloid leukemia (AML) (20.4%) and multiple myeloma (19.7%). Day-90 mortality in patients with HM was higher than in patients with no cancer (64.4% vs. 46.6% p = 0.01) but was not different from that of patients with solid cancer (64.4% vs. 61.4%,p = 0.09). Intubation rate was lower in patients with HM in comparison with both groups (87.7% vs. 90.4% p = 0.02 for patients with solid cancer and 87.7% vs. 91.3%; p < 0.01 with no cancer). Independent predictors of mortality for patients with HM were a diagnosis of lymphoma or acute leukemia, age, a high modified SAPS II score, a renal replacement therapy, invasive fungal infection, and a septic shock. Bacterial pneumonia, extrapulmonary infections and non-invasive ventilation were protective. CONCLUSION: Mortality remains high in patients with HM admitted in ICU with ARDS in comparison with patients without cancer. Mortality predictors for this population were a diagnosis of lymphoma or acute leukemia, age, a high modified SAPS II score, a renal replacement therapy, invasive fungal infection and a septic shock.

Direct reinfusion of pericardial blood complications: A case of acute respiratory distress syndrome and disseminated intravascular coagulation.

Background: Direct reinfusion of pericardial blood during cardiac surgery triggers a systemic inflammatory response. Although various inflammatory mediators have been identified as triggers, the role of damage-associated molecular patterns (DAMPs) remains poorly understood. Despite guidelines recommending against this practice owing to its harmful effects, it is sometimes used in emergencies. Case Presentation: A 72-year-old man with atrial fibrillation and cerebral infarction developed cardiac tamponade during catheter ablation. He underwent pericardial drainage and direct blood reinfusion. He was transferred to our ICU, where he developed acute respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC). Despite aggressive management, the patient died 41 days after admission. Conclusion: This case highlights severe adverse events following direct reinfusion of pericardial blood. These findings suggest a significant role for DAMPs in mediating these inflammatory responses. Direct reinfusion of pericardial drainage blood should be avoided during emergencies to prevent life-threatening complications.