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Postural control can be challenged by breathing. What is the effect of an acute increase in respiratory demand on postural control compared to quiet breathing? A systematic review was conducted. Electronic databases were systematically searched until October 18, 2022 on studies reporting changes in center of pressure (CoP) motion related to an acute manipulation of respiratory demand compared to quiet breathing during upright standing in healthy participants and/or participants with a clinical condition. Twenty-one studies in healthy participants showed that voluntary (not metabolic-induced) hyperventilation or inspiratory resistive loading significantly increased CoP motion, while breath-holding decreased CoP motion, compared to quiet breathing (p< 0.05). Manipulating respiratory rate or breathing patterns did not reveal consistent results. Four studies showed that people with low back pain showed similar CoP responses to increasing respiratory demand (p> 0.05), except for breathing at different rates, whereas they showed greater CoP motion during quiet breathing. The extent of postural disturbance depended on the breathing mode and how it was quantified (i.e., CoP coupled with breathing movement or overall CoP measures). Voluntary hyperventilation and inspiratory resistive loading increased postural sway. For voluntary hyperventilation, this could be explained by CoP motion being directly coupled to chest wall movements whereas metabolic-induced hyperventilation did not increase CoP motion or CoP coupling with breathing. Breath-holding decreased postural sway. Patients with low back pain show greater postural sways than pain-free individuals during quiet breathing, although they exhibit similar postural adaptations to respiratory-related challenges as controls. • Studies assessing the effect of breathing demand on postural control were reviewed • Voluntary (not metabolic-induced) hyperventilation increased postural sway • Inspiratory resistive loading increased postural sway • Breath-holding decreased postural sway • Patients with low back pain show similar responses to increasing breathing demand [ABSTRACT FROM AUTHOR]

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate. The floxed Pten (PtenFL/FL) and myeloid-specific Pten knockout (PtenM−KO) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some PtenM−KO mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from PtenFL/FL and PtenM−KO mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3β) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells. Here, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3β and MST1 binding. Our study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI. [Display omitted] • Myeloid Pten deficiency activate YAP translocation protect against in LPS-induced ALI. • The modulation of the Hippo-YAP pathway by PTEN necessitates the interaction between GSK3β and MST1. • Macrophage PTEN-YAP axis modulates the NRF2 expression. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are attractive as a therapeutic modality in multiple disease conditions characterized by inflammation and vascular compromise. Logistically they are advantageous because they can be isolated from adult tissue sources, such as bone marrow (BM). The phase 2a START clinical trial determined BM-MSCs to be safe in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Herein, we examine a subset of the clinical doses of MSCs generated for the phase 2a START trial from three unique donors (1–3), where one of the donors' donated BM on two separate occasions (donor 3 and 3W). The main objective of this study was to correlate properties of the cells from the four lots with plasma biomarkers from treated patients and relevant to ARDS outcomes. To do this we evaluated MSC donor lots for (i) post-thaw viability, (ii) growth kinetics, (iii) metabolism, (iv) surface marker expression, (v) protein expression, (vi) immunomodulatory ability and (vii) their functional effects on regulating endothelial cell permeability. MSC-specific marker expression and protection of thrombin-challenged endothelial barrier permeability was similar among all four donor lots. Inter and intra-donor variability was observed in all the other in vitro assays. Furthermore, patient plasma ANG-2 and protein C levels at 6 hours post-transfusion were correlated to cell viability in an inter- and intra-donor dependent manner. These findings highlight the potential of donor dependent (inter-) and collection dependent (intra-) effects in patient biomarker expression. [ABSTRACT FROM AUTHOR]

Restoring and maintaining the function of endothelial cells is critical for acute respiratory distress syndrome (ARDS). Guanylate binding protein 1(GBP1) is proved to elevated in ARDS patients, but its role and mechanism remains unclear. The objective of this study is to investigate the internal mechanism of GBP1 in lung injury. Our study showed that when the LPS and IFN-γ induced human Pulmonary Microvascular Endothelial Cells (HPMECs) injury model was established, cell viability was significantly reduced, and the levels of GBP1 levels and inflammatory factors were significantly increased. When transfection with si-GBP1, low expression of GBP1 promoted cell proliferation and migration, and decreased the expression of downstream inflammatory factors. Furthermore, the inhibition of GBP1 significantly reduced the occurrence of cell pyroptosis and the expression of NLRP3 and STAT1. Our study indicated that GBP1 alleviates endothelial pyroptosis and inflammation through STAT1 / NLRP3/GSDMD signaling pathway, and GBP1 may be a new target in the treatment of lung injury in the future. • GBP1 was increased in Inflammation induced HPMECs. • GBP1 is the key to regulate the proliferation and migration of HPMECs. • GBP1 regulate the inflammatory response of HPMECs. • GBP1 may regulate the pyroptosis of HPMECs through regulating STAT1 and NLRP3. [ABSTRACT FROM AUTHOR]

Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs. We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence. Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56–0.87, P =0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48–0.77, P < 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67–1.10, P =0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies. Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery. INPLASY 202410068. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) is a critical respiratory condition characterized by a sudden respiratory collapse, accumulation of fluid in lungs leading to reduced blood oxygenation. ALI/ARDS management is mainly supportive, as no specific anti-inflammatory therapy exists for lung injury. Recently, several medicinal plants and natural products have gained attention for their antimicrobial, antioxidant, immunomodulation and anti-inflammatory activities. Cenchrus ciliaris L. (Buffel grass), is native to Africa and Asia where it is traditionally used for several inflammatory disorders, wounds and pain. Cigarette smoke induces inflammation and oxidative stress in respiratory system which can damage lungs and augment respiratory disorders that can progress to ALI/ARDS. We described antioxidant and anti-inflammatory potential of C. ciliaris L. which ameliorates acute lung injury induced by exposure to cigarette smoke. Total phenolic, flavonoid, tannin and saponin contents were quantified in 70 % methanolic extract of C. ciliaris (Cc.Cr). Phytochemical characterization was performed by UHPLC which indicated the presence of furoic acid, longistylin A, scandenin, salicylic acid, piscidic acid, 3-hydroxybenzaldehyde, pheophorbide and chrysoeriol reported for their antioxidant, anti-inflammatory and antimicrobial activities. ALI was induced in mice by exposure to cigarette smoke, followed by the collection of broncho alveolar lavage fluid (BALF) and lung tissues. Total inflammatory cells, differential leukocyte count, total protein contents, nitrite levels, interleukins, total oxidative stress and antioxidant capacity were assessed in BALF. MDA and catalase levels were assessed in lung tissue and histopathology was performed to assess the integrity of lung tissue architecture. Cc.Cr showed good antioxidant activity in CUPRAC and FRAP assays while it effectively scavenged free radicals in DPPH, ABTS and nitric oxide assay. Cc.Cr inhibited cycloxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) with IC 50 values 29.23 ± 9.73 μ g/ml and 24.12 ± 6.0 μ g/ml respectively. In mice, Cc.Cr improved total antioxidant capacity, lung tissue integrity, and hematological parameters while it reduced inflammation, oxidative stress, lung edema and tissue damage. Graphical abstract [Display omitted] • C. ciliaris L. possess good antioxidant and free radical scavenging activity. • It inhibits COX-2 and 5-LOX enzymes. • C. ciliaris L. improves total antioxidant capacity, lung tissue integrity and hematological parameters. • C. ciliaris L. reduced inflammation, oxidative stress, lung edema and tissue damage in acute lung injury. [ABSTRACT FROM AUTHOR]

Severe COVID-19 can cause acute respiratory distress syndrome, hypoxia, systemic complications, and increased mortality. Pulmonary hypertension (PH) is a major global health issue associated with worsening symptoms and increased mortality. This systematic review aimed to assess the influence of PH onset among COVID-19 patients on all-cause mortality and intensive care unit (ICU) admission. An unrestricted search of five databases up to June 2022 was undertaken. Pulmonary hypertension was assessed using transthoracic echocardiogram, computed tomography, or right heart catheterisation. After duplicate screening, data extraction, and risk of bias assessment, random effects meta-analyses of odds ratios (OR) and their 95% confidence intervals (CI) were performed for all-cause mortality and ICU admission. From the 26 studies that were included (3,373 patients, 76% males, median age 62.6 years), PH in COVID-19 patients was significantly associated with higher odds for all-cause mortality (26 studies; OR 3.89; 95% CI 2.85–5.31; p<0.001) and higher odds for ICU admission (six studies; OR 2.50; 95% CI 1.69–3.70; p<0.001). Meta-regression/subgroup analyses by patient demographics, comorbidities, or therapeutic regimens, and sensitivity analyses did not find any differences. Evidence from observational studies indicates that PH in COVID-19 patients is associated with increased odds of mortality and ICU admission. [ABSTRACT FROM AUTHOR]

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l -arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l -arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l -arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS. [Display omitted] [ABSTRACT FROM AUTHOR]

Minimally invasive (MI) approaches to lung transplantation (LTx) offer the prospect of faster recovery compared to traditional incisions, however, little data exist describing the impact of surgical technique on early outcomes and analgesia use. A prospectively maintained institutional registry identified 170 patients who underwent LTx between January, 2017 and June, 2022. Post-COVID acute respiratory distress syndrome, repeat, and multiorgan transplants were excluded (n = 27) leaving 37 MILTx and 106 traditional LTx patients. Propensity score matching by age, sex, body mass index, diagnosis, lung allocation score, double vs. single lung, hypertension, diabetes, and hospitalization status created 37 pairs. Before matching, MILTx patients were more often male (70% vs 43%) and more likely to receive grafts from younger (31 vs 42 years), circulatory death donors (19% vs 6%) compared with traditional LTx patients (all p < 0.05). After matching, there were no differences in graft warm ischemia or operative duration (both p > 0.05). Postoperatively, MILTx experienced shorter intensive care unit (ICU) (4.3 [IQR 3.1–5.5] vs 8.2 [IQR 3.7–10.8] days) and hospital lengths of stay (LOS) (13 [IQR 11–15] vs 17 [IQR 12–25] days) (both p < 0.05). Among patients surviving to discharge, MILTx patients required fewer opioid prescriptions at discharge (38% vs 66%, p = 0.008) and had improved pulmonary function at 3 months (Forced expiratory volume in 1 second 82 [IQR 72–102] vs 77 [IQR 52–88]% predicted; forced vital capacity 78 [IQR 65–92] vs 70 [IQR 62–80]% predicted] (both p < 0.05). Minimally invasive LTx techniques demonstrate potential advantages over traditional approaches, including reduced ICU and hospital LOS, lower opioid use on discharge, and improved early pulmonary function. [ABSTRACT FROM AUTHOR]

As several recent studies have shown low mortality rates in burn injury induced ARDS early (≤7 days) after the burn, the Berlin criteria for the ARDS diagnosis in this setting may be disputed. Related to this issue, the present study investigated the incidence, trajectory and risk factors of early Acute Respiratory Distress Syndrome (ARDS) and outcome in burn patients, as per the Berlin criteria, along with the concurrent prevalence and influence of inhalation injury, and ventilator-acquired pneumonia (VAP). Over a 2.5-year period, burn patients with Total Burn Surface Area (TBSA) exceeding 10% admitted to a national burn center were included. The subgroup of interest comprised patients with more than 48 h of ventilatory support. This group was assessed for ARDS, inhalation injury, and VAP. Out of 292 admissions, 62 sustained burns > 10% TBSA. Of these, 28 (45%) underwent ventilatory support for over 48 h, almost all, 24 out of 28, meeting the criteria for ARDS early, within 7 days post-injury and with a P a O 2 /F i O 2 (PF) rat i o nadir at day 5. The mortality rate for this early ARDS group was under 10%, regardless of PF ratios (mean TBSA% 34,8%). Patients with concurrent inhalation injury and early ARDS showed significantly lower PF ratios (p < 0.001), and higher SOFA scores (p = 0.004) but without impact on mortality. Organ failure, indicated by SOFA scores, peaked early (day 3) and declined in the first week, mirroring PF ratio trends (p < 0.001). The low mortality associated with early ARDS in burn patients in this study challenges the Berlin criteria's for the early ARDS diagnosis, which for its validity relies on that higher mortality is linked to worsening PF ratios. The finding suggests alternative mechanisms, leading to the early ARDS diagnosis, such as the significant impact of inhalation injury on early PF ratios and organ failure, as seen in this study. The concurrence of early organ failure with declining PF ratios, supports, as expected, the hypothesis of trauma-induced inflammation/multi-organ failure mechanisms contributing to early ARDS. The study highlights the complexity in differentiating between the contributions of inhalation injury to early ARDS and the related organ dysfunction early in the burn care trajectory. The Berlin criteria for the ARDS diagnosis may not be fully applicable in the burn care setting, where the low mortality significantly deviates from that described in the original Berlin ARDS criteria publication but is as expected when considering the actual not very extensive burn injury sizes/Baux scores as in the present study. [Display omitted] • The study revealed that 45% of burn patients with ≥ 10% Total Burn Surface Area (TBSA) required ventilatory support ≥ 48 h. • Inhalation injury, when concurrent with early ARDS, significantly reduced the PaO2/FiO2 (PF) ratios, and increased the overall organ failure rate but did not primarily impact mortality. • A notable early peak in organ failure was observed on day 3, with subsequently a slow decline. This pattern mirrored the trends in PF ratios. • The findings challenge the Berlin criteria for early ARDS diagnosis in burn patients, particularly the link between higher mortality and worsening PF ratios. [ABSTRACT FROM AUTHOR]

[Display omitted] • Neutrophilic inflammation is a critical pathogenic hallmark in ARDS. • Ribociclib, a clinically-used CDK4/6 inhibitor, acts as a novel PDE4 inhibitor to regulate neutrophilic inflammation. • Ribociclib shows therapeutic potential in ARDS. • The drug repurposing of ribociclib provides a promising opportunity for neutrophil-associated diseases, including ARDS. Overwhelming neutrophil activation and oxidative stress significantly contribute to acute respiratory distress syndrome (ARDS) pathogenesis. However, the potential of repurposing ribociclib, a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor used clinically in cancer treatment, for treating neutrophilic ARDS remains uncertain. This study illustrated the ability and underlying mechanism of ribociclib for treating ARDS and neutrophilic inflammation. Primary human neutrophils were used to determine the therapeutic effects of ribociclib on respiratory bursts, chemotactic responses, and inflammatory signaling. In vitro and silico analyses were performed to determine the underlying molecular mechanisms. The potential of ribociclib repurposing was evaluated using an in vivo ARDS model in lipopolysaccharide (LPS)-primed mice. We found that treatment using ribociclib markedly limited overabundant oxidative stress (reactive oxygen species [ROS]) production and chemotactic responses (integrin levels and adhesion) in activated human neutrophils. Ribociclib was also shown to act as a selective inhibitor of phosphodiesterase 4 (PDE4), thereby promoting the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway, leading to the inhibition of extracellular signal-regulated kinase (ERK), c-Jun N -terminal kinase (JNK) phosphorylation, and calcium influx. Notably, prophylactic administration and post-treatment with ribociclib ameliorated neutrophil infiltration, lung inflammation, accumulation of oxidative stress, pulmonary destruction, and mortality in mice with LPS-induced ARDS. We demonstrated for the first time that ribociclib serves as a novel PDE4 inhibitor for treating neutrophilic inflammation and ARDS. The repurposing ribociclib and targeting neutrophilic PDE4 offer a potential off-label alternative for treating lung lesions and other inflammatory conditions. [ABSTRACT FROM AUTHOR]

The global SARS-CoV-2 pandemic led to an increased incidence of post-intubation laryngeal injuries in patients with acute respiratory distress syndrome (ARDS). The primary objective of this study was to identify risk factors for symptomatic laryngeal lesions in patients with Covid-19-related ARDS. The secondary objective was to analyze the progression of these laryngeal lesions. A 21 month nested case-control study was conducted in 3 university hospital centers of the Hospices Civils de Lyon (France). Cases encompassed all patients intubated for Covid-19-related ARDS who presented symptomatic laryngeal pathology. The control group consisted of all patients enrolled during the same period for Covid-19-related ARDS without evidence of laryngeal lesions (no specific ENT intervention). Uni- and multi-variate analyses were performed to identify risk factors for the occurrence of laryngeal lesions. Forty-nine patients were included in the case group and 50 in the control group. The only significant risk factor for symptomatic laryngeal injury was the number of reintubations, with an odds ratio of 5.08 (95% CI, 1.40–22.12; P = 0.013). No other predictive factors were identified among the variables analyzed: obesity, number of prone sessions, self-extubation, duration of intubation and number of days of curarization. The number of reintubations was the sole independent risk factor associated with the development of symptomatic laryngeal lesions in patients managed for Covid-19-related ARDS. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is an acute and severe clinical complication lacking effective therapeutic interventions. The disruption of the lung epithelial barrier plays a crucial role in ARDS pathogenesis. Recent studies have proposed the involvement of abnormal mitochondrial dynamics mediated by dynamin-related protein 1 (Drp1) in the mechanism of impaired epithelial barrier in ARDS. Hydrogen is an anti-oxidative stress molecule that regulates mitochondrial function via multiple signaling pathways. Our previous study confirmed that hydrogen modulated oxidative stress and attenuated acute pulmonary edema in ARDS by upregulating thioredoxin 1 (Trx1) expression, but the exact mechanism remains unclear. This study aimed to investigate the effects of hydrogen on mitochondrial dynamics both in vivo and in vitro. Our study revealed that hydrogen inhibited lipopolysaccharide (LPS)-induced phosphorylation of Drp1 (at Ser616), suppressed Drp1-mediated mitochondrial fission, alleviated epithelial tight junction damage and cell apoptosis, and improved the integrity of the epithelial barrier. This process was associated with the upregulation of Trx1 in lung epithelial tissues of ARDS mice by hydrogen. In addition, hydrogen treatment reduced the production of reactive oxygen species in LPS-induced airway epithelial cells (AECs) and increased the mitochondrial membrane potential, indicating that the mitochondrial dysfunction was restored. Then, the expression of tight junction proteins occludin and zonula occludens 1 was upregulated, and apoptosis in AECs was alleviated. Remarkably, the protective effects of hydrogen on the mitochondrial and epithelial barrier were eliminated after applying the Trx1 inhibitor PX-12. The results showed that hydrogen significantly inhibited the cell apoptosis and the disruption of epithelial tight junctions, maintaining the integrity of the epithelial barrier in mice of ARDS. This might be related to the inhibition of Drp1-mediated mitochondrial fission through the Trx1 pathway. The findings of this study provided a new theoretical basis for the application of hydrogen in the clinical treatment of ARDS. [Display omitted] • Hydrogen could alleviate impaired lung epithelial barrier in Acute Respiratory Distress Syndrome (ARDS). • Drp1-mediated mitochondrial fission in ARDS is a compensatory mechanism. • Hydrogen alleviates ARDS lung injury via inhibiting Drp1-mediated mitochondrial fission through the Trx1 pathway. [ABSTRACT FROM AUTHOR]

• Computer simulations and the Lipinski rule evaluate the pharmacokinetic and toxicological aspects of methyl eugenol as a drug candidate. • Treatment with methyl eugenol (ME) during and after the initiation of acute respiratory distress syndrome (ARDS) can prevent the progression of acute inflammation. • In vivo and in silico tests indicate that ME oil is an orally bioavailable drug that exerts multifunctional cytoprotective activities. • ME oil can treat and prevent intestinal I/R-induced ARDS in rats. Acute respiratory distress syndrome (ARDS) is an inflammatory disease that affects the lungs with rupture of the alveolar-capillary barrier and loss of lung compliance, orchestrated by an intense inflammatory process mediated by neutrophils that culminates in diffuse alveolar data and tissue hypoxia. In this context, no specific drug has yet been applied to treat the syndrome. Therefore, finding new therapeutic targets that can treat the syndrome has become a research study. In view of this, methyl-eugenol (ME) has become the target of this study. The aim of this work was to carry out an in silico pharmacological and toxicological analysis with ADMET, as well as to determine, by means of molecular docking, the interaction affinity of the 5-LOX and COX-2 enzymes with ME and then the in vivo tests; in which male rats were distributed into five groups with five rats each, in which some groups were subjected to the process of ischemia and reperfusion (I/R). Groups G4 and G5 were treated by inhalation with ME (10 %). After completing these procedures, statistical analysis and lung histology were carried out. In the ADMET prediction, ME showed high intestinal absorption and a medium-permeability blood-brain barrier. ME had no violations of Lipinski's rule, demonstrating high potential as a drug candidate. Molecular docking showed that ME had the highest binding affinity with the 5-LOX enzyme. Finally, the statistical and histological analyses of the in vivo test showed acute and accentuated lung damage in the G1 group, while in the G4 and G5 groups, ME showed pharmacological efficacy, reducing the number of inflammatory cells, free macrophages and free radicals. The results indicate that ME oil is a favorable therapeutic approach in the treatment of ARDS. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) due to severe coronavirus disease 2019 (COVID-19) pneumonia is associated with a high incidence of ventilator-associated pneumonia (VAP). We aimed to evaluate the epidemiology of VAP associated with severe COVID-19 pneumonia. This retrospective observational study recruited patients with COVID-19-associated ARDS admitted to our center from April 1, 2020, to September 30, 2021. The primary outcome was the survival-to-discharge rate. The secondary outcomes were the VAP rate, time to VAP, length of ICU stay, length of ventilator support, and isolated bacteria. Sixty-eight patients were included in this study; 23 developed VAP. The survival-to-discharge rate was 60.9 % in the VAP group and 84.4 % in the non-VAP group. The median time to VAP onset was 16 days. The median duration of ventilator support and of ICU stay were higher in the VAP group than in the non-VAP group. The VAP rate was 33.8 %. The most common isolated species was Stenotrophomonas maltophilia. On admission, carbapenems were used in a maximum number of cases (75 %). Furthermore, the median body mass index (BMI) was lower and the median sequential organ failure assessment (SOFA) score on admission was higher in the VAP group than in the non-VAP group. The survival-to-discharge rate in VAP patients was low. Moreover, VAP patients tended to have long ICU stays, low BMI, and high SOFA scores on admission. Unusually, S. maltophilia was the most common isolated bacteria, which may be related to the frequent use of carbapenems. [ABSTRACT FROM AUTHOR]

The purpose of this systematic review was to characterize the association between tobacco use and postoperative outcomes, complications, and revision rates following shoulder arthroplasty through a systematic review of the literature. The PubMed/MEDLINE and Embase databases were queried for studies published between January 1, 1985, and April 18, 2023, comparing outcomes following both anatomic and reverse total shoulder arthroplasty (TSA) between tobacco users and nontobacco users. Studies with a level of evidence IV or greater were included, while case reports, systematic reviews, basic science studies, and studies including revision arthroplasty were excluded. American Shoulder and Elbow Surgeons scores, simple shoulder test scores, visual analog scale for pain, complications, readmissions, and reoperations were reported. A total of 20 unique studies including 338,117 shoulder arthroplasties (38,225 [11.3%] performed on tobacco users) were included in this review. Patient-reported outcome measures, including American Shoulder and Elbow Surgeons, simple shoulder test, and visual analog scale, were overall superior in nontobacco users compared to tobacco users. Similarly, tobacco users had lower patient acceptable symptomatic state achievement, worse Single Assessment Numeric Evaluation scores (odds ratio 0.647; 95% confidence interval, 0.324-1.293; P =.0221), and worse constant scores (odds ratio, 0.478; 95% confidence interval, 0.251-0.909; P =.027). Tobacco users demonstrated a higher rate of complications in four of the eight included studies. Two included studies found higher rates of readmission in tobacco users (15.3% vs. 13.6%, P =.007 and 7.8% vs. 7.1%, P =.001), though six included studies found no significant difference in readmissions. Nine of 11 studies that included reoperation as a variable found higher rates of reoperation in tobacco users, with three reaching statistical significance (P <.05). Tobacco users experienced higher rates of gastrointestinal complications (0.07% vs. 0.01%, P =.021), acute renal failure (2.5% vs. 1.9%, P =.005), acute respiratory distress (1.3% vs. 0.9%, P =.002), need for ventilator assistance (1.2% vs. 0.7%, P <.001), instability of the prosthesis (P <.001), pneumonia (P <.001), sepsis (P =.001), and myocardial infarction (P <.001). Smokers also demonstrated increased postoperative opioid use (2643 mg oral morphine equivalents) compared to nonsmokers (2121 mg) and former smokers (2015 mg; P =.04). Tobacco use is associated with inferior outcomes after TSA, including lower patient-reported outcome measures, increased complications, and higher reoperation rates. Further high-level, prospective studies with long-term follow-up are required to further elucidate the impact of tobacco use on long-term postoperative outcomes following TSA. [ABSTRACT FROM AUTHOR]

COVID-19 vaccines have reduced the risk of disease progression to respiratory failure or death. However, in patients with breakthrough infections requiring invasive mechanical ventilation, the effect of prior COVID-19 vaccination on mortality remains inconclusive. We retrospectively analyzed data on patients intubated due to COVID-19 pneumonia between May 1, 2022 and October 31, 2022. Receipt of two or more doses of vaccine were considered as fully vaccinated. The primary outcome was the time from intubation to all-cause intensive care unit (ICU) mortality. A total of 84 patients were included (40 fully vaccinated versus 44 controls). The baseline characteristics, including age, comorbidities, and Sequential Organ Failure Assessment (SOFA) score on the day of intubation were similar between the two groups. The difference in ICU mortality rate between the fully vaccinated and control groups was not significant (35 % vs. 25 %, P = 0.317; hazard ratio with 95 % confidence interval = 1.246 (0.575–2.666), P = 0.571). The SOFA score (hazard ratio: 1.319, P = 0.001) and body mass index (BMI) (hazard ratio: 0.883, P = 0.022) were significantly associated with ICU mortality. Being fully vaccinated was not associated with a mortality benefit in intubated patients with COVID-19. A higher SOFA score on the day of intubation and lower BMI were poor prognostic factors. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a critical illness characterized by severe lung inflammation. Improving the delivery efficiency and achieving the controlled release of anti-inflammatory drugs at the lung inflammatory site are major challenges in ARDS therapy. Taking advantage of the increased pulmonary vascular permeability and a slightly acidic-inflammatory microenvironment, pH-responsive mineralized nanoparticles based on dexamethasone sodium phosphate (DSP) and Ca2+ were constructed. By further biomimetic modification with M2 macrophage membranes, hybrid mineralized nanovesicles (MM@LCaP) were designed to possess immunomodulatory ability from the membranes and preserve the pH-sensitivity from core nanoparticles for responsive drug release under acidic inflammatory conditions. Compared with healthy mice, the lung/liver accumulation of MM@LCaP in inflammatory mice was increased by around 5.5 times at 48 h after intravenous injection. MM@LCaP promoted the polarization of anti-inflammatory macrophages, calmed inflammatory cytokines, and exhibited a comprehensive therapeutic outcome. Moreover, MM@LCaP improved the safety profile of glucocorticoids. Taken together, the hybrid mineralized nanovesicles-based drug delivery strategy may offer promising ideas for enhancing the efficacy and reducing the toxicity of clinical drugs. Hybrid mineralized nanovesicles improved the drug delivery efficiency to the lungs, suppressed the inflammatory conditions effectively, and meanwhile reduced side effects of glucocorticoids. [Display omitted] • Dexamethasone-based mineralized nanoparticles achieved pH-responsive drug release behavior. • Biomimetic modification enhanced immunomodulatory ability. • Hybrid mineralized nanovesicles increased lung accumulation based on ELVIS effect and improved the safety profile of glucocorticoids. [ABSTRACT FROM AUTHOR]

In the progression of acute inflammation, the activation and recruitment of macrophages and neutrophils are mutually reinforcing, leading to amplified inflammatory response and severe tissue damage. Therefore, to regulate the axis of neutrophils and macrophages is essential to avoid tissue damage induced from acute inflammatory. Apoptotic neutrophils can regulate the anti-inflammatory activity of macrophages through the efferocytosis. The strategy of in situ targeting and inducing neutrophil apoptosis has the potential to modulate macrophage activity and transfer anti-inflammatory drugs. Herein, a natural glycyrrhiza protein nanoparticle loaded with dexamethasone (Dex@GNPs) was constructed, which could simultaneously regulate neutrophil and macrophage function during acute inflammation treatment by combining in situ neutrophil apoptosis and macrophage efferocytosis. Dex@GNPs can be rapidly and selectively internalized by neutrophils and subsequently induce neutrophils apoptosis through a ROS-dependent mechanism. The efferocytosis of apoptotic neutrophils not only promoted the polarization of macrophages into anti-inflammatory state, but also facilitated the transfer of Dex@GNPs to macrophages. This enabled dexamethasone to further modulate macrophage function. In mouse models of acute respiratory distress syndrome and sepsis, Dex@GNPs significantly ameliorated the disordered immune microenvironment and alleviated tissue injury. This study presents a novel strategy for drug delivery and inflammation regulation to effectively treat acute inflammatory diseases. [Display omitted] • Glycyrrhiza protein nanoparticles could specifically target neutrophils and induce their apoptosis. • Neutrophil hitchhiking and macrophage efferocytosis are combined to drive inflammation targeting and delivery of drugs. • Macrophages and neutrophils are simultaneously regulated according to their different effects in inflammation. • Dex@GNPs ameliorate the disordered immune microenvironment and alleviate tissue injury in ARDS and sepsis. [ABSTRACT FROM AUTHOR]

Noninvasive methods of respiratory support, including noninvasive ventilation (NIV), continuous positive airway pressure (CPAP), and high-flow nasal oxygen (HFNO), are potential strategies to prevent progression to requirement for invasive mechanical ventilation in acute hypoxaemic respiratory failure. The COVID-19 pandemic provided an opportunity to understand the utility of noninvasive respiratory support among a homogeneous cohort of patients with contemporary management of acute respiratory distress syndrome. We performed a network meta-analysis of studies evaluating the efficacy of NIV (including CPAP) and HFNO, compared with conventional oxygen therapy (COT), in patients with COVID-19. PubMed, Embase, and the Cochrane library were searched in May 2023. Standard random-effects meta-analysis was used first to estimate all direct pairwise associations and the results from all studies were combined using frequentist network meta-analysis. Primary outcome was treatment failure, defined as discontinuation of HFNO, NIV, or COT despite progressive disease. Secondary outcome was mortality. We included data from eight RCTs with 2302 patients, (756 [33%] assigned to COT, 371 [16%] to NIV, and 1175 [51%] to HFNO). The odds of treatment failure were similar for NIV (P =0.33) and HFNO (P =0.25), and both were similar to that for COT (reference category). The odds of mortality were similar for all three treatments (odds ratio for NIV vs COT: 1.06 [0.46–2.44] and HFNO vs COT: 0.97 [0.57–1.65]). Noninvasive ventilation, high-flow nasal oxygen, and conventional oxygen therapy are comparable with regards to treatment failure and mortality in COVID-19-associated acute respiratory failure. CRD42023426495. [ABSTRACT FROM AUTHOR]

Air leak syndrome (ALS) is described in human medicine as a constellation of clinical disorders including pneumomediastinum, pneumopericardium, pulmonary interstitial emphysema, pneumothorax, pneumoperitoneum, pneumoretroperitoneum and subcutaneous emphysema. The pathogenesis of ALS depends on the anatomy of the mediastinum and its associations with thoracic, abdominal and cervical connective tissues, as well as a physical phenomenon referred to as the Macklin effect. Various animal species develop diverse combinations of these lesions, although ALS has not been recognized in animals. However, this term aids pathologists in addressing this disease compilation. The aim of this retrospective study is to illustrate examples of ALS in animals by arbitrarily selecting 13 cases in dogs, cats, pinnipeds, sea otters and harbour porpoises. ALS can be classified into three groups based on aetiology: iatrogenic, secondary or spontaneous. Iatrogenic ALS was diagnosed in two cats with tracheal laceration following endotracheal intubation. Secondary ALS was identified in two dogs, one with acute respiratory distress syndrome and the other due to grass awn migration. Secondary ALS in pinnipeds was diagnosed following severe pulmonary parasitism, uraemic pneumonia and oesophageal perforation. The other marine mammals developed ALS following trauma. Spontaneous ALS was also diagnosed in one cat and one dog without any apparent predisposing causes. [ABSTRACT FROM AUTHOR]

Direct thrombin inhibitors, including argatroban, are increasingly used for anticoagulation during venovenous extracorporeal membrane oxygenation (VV ECMO). In many centers activated partial thromboplastin time (aPTT) is used for monitoring, but it can be affected by several confounders. The aim of this study was to evaluate the safety and efficacy of anticoagulation with argatroban titrated according to diluted thrombin time targets (hemoclot™ assay) compared to anti-Xa guided anticoagulation with unfractionated heparin (UFH). This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4–0.6 μg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2–0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range). From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44–2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26–0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23–54 %) vs. 46 % (37 %–57 %), p = 0.45). Anticoagulation with argatroban according to hemoclot™ targets (0.4–0.6 μg/ml) compared to antiXa guided UFH (0.2–0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO. [Display omitted] • Time to first clinically relevant bleeding was similar in patients treated with argatroban and unfractionated heparin • Argatroban was associated with a reduced risk of thromboembolism compared to unfractionated heparin • The overall proportion of anticoagulation within target ranges did not differ between groups [ABSTRACT FROM AUTHOR]

The high infection rate and mortality associated with novel coronavirus infections have attracted worldwide attention; however, the impact of the novel coronavirus on patients with a history of renal transplantation has not been investigated thoroughly. This report presents a patient with SARS-CoV-2 pneumonia following kidney transplantation. The patient developed acute respiratory distress syndrome and acute renal failure upon infection. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient successfully recovered and her renal function returned to normal. This report provides a reference for the treatment of similar patients. [ABSTRACT FROM AUTHOR]

To ascertain the association between body composition, including muscle mass and adiposity, and patient mortality in those requiring extracorporeal membrane oxygenation (ECMO) for acute respiratory failure. A retrospective study was undertaken of all patients with acute respiratory failure requiring veno-venous (VV) ECMO between January 2015 and December 2019. Automated image segmentation software was used to quantify the cross-sectional area and average radiodensity (in Hounsfield units) of different muscle and fat compartments at the L3 level of whole-body computed tomography (CT) images taken within 48 h of initiation of ECMO support. The primary endpoint was 30-day post-ECMO initiation all-cause mortality. Logistic regression was used to analyse the correlation between CT measurements, co-morbidities, and 30-day survival. The study included 189 patients (age = 43.8 ± 14.6, sex = 42.3% female). There was no significant association between 30-day survival status and cross-sectional area of muscle or fat. Muscle attenuation (psoas, long spine, and abdominal muscles respectively) at the L3 level were significantly lower in those who died within 30 days of ECMO cannulation (p <0.05). On multivariable analysis including age, sex, and pre-existing respiratory comorbidities, psoas muscle attenuation was an independent predictor of survival at 30 days (OR 0.97; 95% CI 0.94 to 1.00; p =0.047). Reduced psoas muscle attenuation is associated with poorer survival outcomes at 30 days post-ECMO cannulation in patients who received VV ECMO support for respiratory failure. Cross-sectional areas of muscle and fat compartments did not correlate with survival outcomes at 30 days even when corrected for height and sex. • Neither muscle nor fat volumes were associated with outcomes. • Muscle attenuation was lower in those who died within 30 days of ECMO cannulation. • Psoas muscle attenuation was an independent predictor of survival at 30 days. [ABSTRACT FROM AUTHOR]

After reading the article, the reader will be able to: • Understand the rationale behind using positive end-expiratory pressure in ventilated patients. • Understand the potential adverse effects of positive end-expiratory pressure. • Identify key steps for individualized titration of positive end-expiratory pressure. Application of positive end-expiratory pressure (PEEP) targeted towards improving oxygenation is one of the components of the ventilatory management of pediatric acute respiratory distress syndrome (PARDS). Low end-expiratory airway pressures cause repetitive opening and closure of unstable alveoli, leading to surfactant dysfunction and parenchymal shear injury. Consequently, there is less lung volume available for tidal ventilation when there are atelectatic lung regions. This will increase lung strain in aerated lung areas to which the tidal volume is preferentially distributed. Pediatric critical care practitioners tend to use low levels of PEEP and inherently accept higher FiO 2 , but these practices may negatively affect patient outcome. The Pediatric Acute Lung Injury Consensus Conference (PALICC) suggests that PEEP should be titrated to oxygenation/oxygen delivery, hemodynamics, and compliance measured under static conditions as compared to other clinical parameters or any of these parameters in isolation in patients with PARDS, while limiting plateau pressure and/or driving pressure limits. [ABSTRACT FROM AUTHOR]

Many patients with severe COVID-19 have been affected by acute respiratory distress syndrome, which has been associated with increased mortality, and up to 31% of these survivors had persistent interstitial lung abnormalities with impaired lung function and quality of life even after 6 to 24 months after initial disease. Lung transplantation quickly emerged as a viable therapy for select patients with respiratory failure due to COVID-19 by mid-2020. In this report, we identified 477 patients who underwent lung transplantation for COVID-19 in the U.S. between March 2020 and December 2022. The number of patients waitlisted and undergoing lung transplantation for COVID-19 increased steadily in the early part of the pandemic with a peak of 97 patients waitlisted between October and December 2021, before steadily decreasing since. Notably, the procedure is now increasingly being done for survivors of COVID-19 with pulmonary fibrosis, rather than for refractory ARDS patients. The 1-year post-transplant mortality was 13.7%. [ABSTRACT FROM AUTHOR]

Psychological impact of Medical Evacuation (MEDEVAC) in Covid-19 patients is undetermined. The objectives were to evaluate: Post-traumatic Stress Disorder (PTSD) in MEDEVAC patients hospitalized in ICU for Covid-19-related acute respiratory distress syndrome (ARDS) compared to control group; anxiety, depression rates and outcomes in patients and PTSD in relatives. This is a retrospective multicentric 1/1 paired cohort performed in 10 ICUs in the West of France. Evaluation was performed 18 months after discharge. Patients and closest relatives performed IES-R (Impact and Event Scale-Revised) and/or HADS (Hospital Anxiety and Depression Scale) scales. Twenty-six patients were included in each group. Patients were 64 ± 11 years old, with 83% male. We report 12 vs 20% of PTSD in control vs MEDEVAC groups (p = 0.7). Anxiety disorder affected 43.5 vs 28.0% (p = 0.26) and depression 12.5 vs 14.3% (p > 0.99) in control vs MEDEVAC groups. PTSD affects 33.3 vs 42.1% of closest relatives (p = 0.55). Ways of communication were adapted: video calls were more frequent in MEDEVAC patients (8.7 vs 60.9%, p < 0.01) whereas physical visits concerned more control group (45.8 vs 13.0%, p = 0.01). PTSD rate were similar between groups. Adaptive ways of communication, restricted visits and global uncertainties could explain the absence of differences. • Medical evacuation was not associated with increased PTSD, anxiety or stress disorders in ICU patients. • Medical evacuation was associated with adaptative ways of communication. • Medical evacuation did not affect PTSD rate in closest relatives of ICU patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • The LPS-induced tree shrews exhibited severe shortness of breath, resulting in hypoxemia. • The induced group of animals exhibited 72 ∼ 120 h endpoints, and none of them recover. • Diffuse alveolar damage was observed in the lungs of the tree shrew, which is the histological hallmark for the acute phase of ARDS. • 3D reconstruction of the lung CT images was used to accurately measure the extent and distribution of the whole lung injury in LPS-induced tree shrews. Acute respiratory distress syndrome (ARDS) is a leading cause of respiratory failure, with substantial attributable morbidity and mortality. The small animal models that are currently used for ARDS do not fully manifest all of the pathological hallmarks of human patients, which hampers both the studies of disease mechanism and drug development. To examine whether the phenotypic changes of primate-like tree shrews in response to a one-hit lipopolysaccharides (LPS) injury resemble human ARDS features. LPS was administered to tree shrews through intratracheal instillation; then, the animals underwent CT or PET/CT imaging to examine the changes in the structure and function of the whole lung. The lung histology was analyzed by H&E staining and immunohistochemical staining of inflammatory cells. Results demonstrated that tree shrews exhibited an average survival time of 3–5 days after LPS insult, as well as an obvious symptom of dyspnea before death. The ratios of PaO 2 to FiO 2 (P/F ratio) were close to those of moderate ARDS in humans. CT imaging showed that the scope of the lung injury in tree shrews after LPS treatment were extensive. PET/CT imaging with 18F-FDG displayed an obvious inflammatory infiltration. Histological analysis detected the formation of a hyaline membrane, which is usually present in human ARDS. This study established a lung injury model with a primate-like small animal model and confirmed that they have similar features to human ARDS, which might provide a valuable tool for translational research. [ABSTRACT FROM AUTHOR]

Patients with cerebral venous sinus thrombosis (CVST) may die during the acute phase due to increased intracranial pressure and cerebral herniation. The purpose of this study was to assess the role of decompressive craniectomy in the treatment of patients with malignant CVST. Patients who underwent decompressive craniectomy and were consequently admitted to the Critical Care Unit, Department of Neurosurgery, at Capital Medical University Xuanwu Hospital from March 2010 to January 2021 were retrospectively examined with follow-up data at 12 months. In total, 14 cases were reviewed, including 9 female and 5 male patients, aged 23–63 years (42.7 ± 12.3 years). Prior to surgery, all patients had a GCS score <9. 6 patients had a unilateral dilated pupil, while 4 patients had bilateral dilated pupils. According to the head computed tomography (CT), all patients had hemorrhagic infarction, and the median midline shift was 9.5 mm before surgery. Thirteen patients underwent unilateral decompressive craniectomy, and 1 patient underwent bilateral decompressive craniectomy, among whom, 9 patients underwent hematoma evacuation. Within 3 weeks of surgery, 3 cases (21.43%) resulted in death, with 2 patients dying from progressive intracranial hypertension and 1 from acute respiratory distress syndrome (ARDS). Eleven patients (78.57%) survived after surgery, of whom 4 (28.57%) patients recovered without disability at 12-month follow-up (mRS 0–1), 2 (14.29%) patients had moderate disability (mRS 2–3), and 5 (35.71%) patients had severe disability (mRS 4–5). Emergent decompressive craniectomy may provide a chance for survival and enable patients with malignant CVST to achieve an acceptable quality of life (QOL). [ABSTRACT FROM AUTHOR]

[Display omitted] Among patients who suffer from lung-related disability, acute respiratory distress syndrome (ARDS) is one of the diseases with the significant mortality rate and the main cause is the interference in pulmonary drug delivery by accumulated bronchoalveolar lavage fluid (BALF) in the alveolar region. Here, a zwitterion-functionalized multi-drug nanocomplex (ZnC) capable of anti-mucociliary clearance was synthesized. Additionally, nitric oxide (NO) was functionalized with ZnC to fuel the mobility in the BALF through its role as a nanomotor as well as anti-inflammation. Subsequently, dexamethasone (Dex) was loaded and final product of anti-inflammatory mucus permeator (AIM) was introduced. By in situ tracking the AIM within the mucus-rich environment, the fueled mobility by NO and zwitterion was demonstrated. Notably, when AIM was inhaled by the in vivo ARDS model, there was an increase in the anti-inflammation effect due to the presence of ZnC as well as the synergy between NO and Dex, which recovered the pulmonary function of the model and increased survival rate. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (group B streptococcus; GBS) is a Gram-positive coccus. It has emerged as a cause of significant infections in non-pregnant adults, particularly neonates and individuals aged 65 years or older, which can lead to fatal outcomes. Streptococcal toxic shock-like syndrome (STSS) is an acute illness, which is mainly caused by exotoxin-producing strains of Streptococcus pyogenes and may result in death. In this report, we present a fatal non-pregnant case of STSS induced by GBS in a 45-year-old healthy female. The patient presented with fever, polyarthralgia, myalgia, and skin erythema. Matrix Assisted Laser Desorption/Ionization‒Time of Flight Mass Spectrometry (MALDI-TOF-MS) and PCR identified GBS in colonies from her blood and urine cultures, and she was diagnosed with septicemia and STSS. On the sixth day of her illness, she died from acute respiratory distress syndrome and multiple organ dysfunction syndrome. Whole-genome sequencing revealed the presence of several virulence genes in the genome of the GBS strain detected in the blood cultures, which may have contributed to the development of STSS and the patient's death. [ABSTRACT FROM AUTHOR]

• The rs4986790 GG genotype of the toll-like receptor 4 is associated with the risk of COVID-19. • GG genotype (rs4986790) had a limited delivery of pro-inflammatory markers. • The AA and AG genotypes induce interleukin-10, interleukin-6, tumor necrosis factor-α, and Fas ligand production. • B-cell subpopulations are unaffected in patients with the GG genotype. • Patients with COVID-19, carrying the allele risk, secrete high levels of cytotoxic proteins. We investigated the expression of toll-like receptor (TLR)-4 on the cell surface of innate and adaptive cells from patients with COVID-19 carrying the rs4986790 GG genotype in the TLR4 gene and the functional profile of these cells. We included 1169 hospitalized patients with COVID-19. The rs4986790 in TLR4 was identified by real-time polymerase chain reaction. Peripheral blood mononuclear cells were isolated and cultured to evaluate TLR-4 expression on immune cells. Supernatants recovered culture assays were stored, and we measured cytokines and cytotoxic molecules. We showed that the rs4986790 (GG) was significantly associated (P = 0.0310) with severe COVID-19. Cells of patients with COVID-19 carrying the GG genotype have increased the frequency of monocytes and activated naïve and non-switched B cells positive to TLR-4 when cells are stimulated with lipopolysaccharide and with spike protein of SARS-CoV-2. Also, cells from patients with GG COVID-19 cannot produce pro-inflammatory cytokines after lipopolysaccharide stimulus, but they are high producers of cytotoxic molecules at baseline. The rs4986790 GG genotype of the TLR4 is associated with the risk of COVID-19 and acute respiratory distress syndrome. Peripheral blood mononuclear cells of patients carrying the rs4986790 (TLR4) GG genotype had a limited delivery of pro-inflammatory cytokines compared to the AA and AG genotypes in which TLR-4 stimulation induces IL-10, IL-6, tumor necrosis factor-α, and Fas ligand production. [ABSTRACT FROM AUTHOR]

We report a non-ambulatory 13-year-old boy with Duchenne muscular dystrophy who experienced severe acute respiratory distress syndrome and cerebral fat embolism following elective soft tissue surgery. Post-surgery radiological examination revealed bilateral femoral fractures and marked osteopenia that were believed to have caused disseminated pulmonary and cerebral fat embolism. The patient had never been on glucocorticoid treatment. Five months post-surgery, he remained in a state of minimal consciousness. A literature review was performed and eleven publications included, providing case reports of a total number of 23 patients with Duchenne muscular dystrophy with fat embolism syndrome. The most common causes were falls from the wheelchair that predominantly resulted in femoral fractures. Median age at the event was around 14 years. Seven patients succumbed to complications of fat embolism. No event was described in the context of surgery. We want to raise awareness that spontaneous unnoticed fractures may occur especially in adolescents with DMD from traumatic injury of large bones and also during elective surgery with a high risk of causing fat embolism with severe sequelae. • Spontaneous unnoticed fractures may occur in DMD due to osteoporosis during elective surgery, facilitating fat embolism. • The incidence of FES is higher in DMD compared with the healthy population and other genetic neuromuscular conditions. • The clinical outcome after FE in individuals with DMD seems to be less positive than in the general population. • The acute imaging pattern on susceptibility-weighted MR-imaging, FLAIR and DWI mimics the clinical picture seen in traumatic diffuse axonal injury. • Elective surgery in DMD should be carefully considered. [ABSTRACT FROM AUTHOR]

The article explores the utilization of corticosteroids in adults dealing with acute respiratory distress syndrome (ARDS) and severe pneumonia and delves into the impact of corticosteroids on ARDS, pneumonia treatment, and their role in managing severe respiratory conditions in adult patients.

Increased endothelial cell (EC) permeability is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Tyrosine phosphorylation of VE-cadherin is a key determinant of EC barrier disruption. However, the identity and role of tyrosine kinases in this context are incompletely understood. Here we report that Spleen Tyrosine Kinase (Syk) is a key mediator of EC barrier disruption and lung vascular leak in sepsis. Inhibition of Syk by pharmacological or genetic approaches, each reduced thrombin-induced EC permeability. Mechanistically, Syk associates with and phosphorylates VEcadherin to cause EC permeability. To study the causal role of endothelial Syk in sepsis-induced ALI, we used a remarkably efficient and cost-effective approach based on gene transfer to generate EC-ablated Syk mice. These mice were protected against sepsis-induced loss of VE-cadherin and inflammatory lung injury. Notably, the administration of Syk inhibitor R788 (fostamatinib); currently in phase II clinical trial for the treatment of COVID-19, mitigated lung injury and mortality in mice with sepsis. These data identify Syk as a novel kinase for VE-cadherin and a druggable target against ALI in sepsis. [ABSTRACT FROM AUTHOR]

Mechanical ventilation is an essential respiratory support in acute respiratory distress syndrome and intensive care cases. However, it is possible to cause ventilator-induced lung damage (VILI). In this work, we used a microfluidic device to provide a mechanical ventilation with cyclic stretch (30% total area change rate and 15 cycles per min) and oxygen (air) flux applied by a controlled pressured airflow. Compared to static control, the ventilation stretch resulted in significant death of A549 cells accompanied by increased lipid peroxidation, mitochondrial reactive oxygen species (ROS) production, and ferrous ion accumulation, while by decreased protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) proteins, as well as ratio of reduced-to-oxidized glutathione. The resulted A549 cell death could be alleviated by two ferroptosis inhibitors, deferoxamine and ferrostatin-1. These similar phenomena also occurred in other three types of human lung cells, such as primary alveolar type II epithelial cells, primary alveolar microvascular endothelial cells, and bronchial epithelial cell line. From the A549 RNA sequence analysis, the gene ontology (GO) based on 85 ferroptosis-related genes (FRGs) indicated that several iron homeostasis-related biological processes and molecular functions were involved in the ventilation-stretch-induced cell death, while the gene set enrichment analysis (GSEA) based on 2901 differentially expressed genes (DEGs) showed that glutathione metabolism was significantly suppressed. Finally, solute carrier family 39 member 14 (SLC39A14), a transporter of uptake extracellular divalent metal ion, was selected to be knocked down to verify its role in the ventilation-stretch-induced death of A549. Our results suggest that ferroptosis may be an alternative pathway for VILI, but it needs to be confirmed by further animal experiments and clinical data. [Display omitted] • Lung cell damage caused by in vitro ventilation stretch is proven to be related to ferroptosis. • Ventilation stretch exacerbates lipid peroxidation of cell membrane by inhibiting the expression of SLC7A11 and GPX4 proteins. • Ventilation stretch-induced ferroptosis in A549 cells is associated with iron ion accumulation caused by upregulation of SLC39A14 expression. • Inhibition of ferroptosis may be used as a potential therapy to relieve ventilator-induced lung injury. [ABSTRACT FROM AUTHOR]

Burns of the chest region constitute a common burn and develops skin contractures around the thorax region. Inhalation of toxic gases and chemical irritants during the fire leads to Acute Respiratory Distress Syndrome (ARDS). Breathing exercises are painful but are needed to help counteract contractures and increase lung capacity. These patients are usually in pain and extremely anxious about chest physiotherapy. Virtual reality distraction is one such technique that is gaining immense popularity when compared to other pain distraction techniques. However, studies examining the efficacy of the virtual reality distraction technique in this population are lacking. To find and compare the effects of the virtual reality distraction technique as a pain alleviation tool for reducing pain during chest physiotherapy in chest burns patients with ARDS in middle-aged adults. A randomized controlled study was conducted at the physiotherapy department between 1st Sep 2020 and 30th Dec 2022. The eligible sixty subjects were randomized into two groups: The virtual reality distraction group (n = 30) received virtual reality distraction technique and the control group (n = 30) received progressive relaxation technique before chest physiotherapy as a pain distraction technique. All the participants received chest physiotherapy as a common treatment (treatment as usual). Primary (Visual Analogue Scale – VAS) and secondary (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, peak expiratory flow (PEF), residual volume (RV), functional residual capacity (FRC), total lung capacity (TLC), RV/TLC, and diffusing capacity for carbon monoxide of the lungs (DLCO) outcome measures were measured at baseline, after four weeks, eight weeks and at six months follow up. The effects between the two groups were analyzed using the independent t-test and chi-square test. The intra-group effect was analyzed with a repeated measure ANOVA test. Baseline demographic characters and study variables show homogenous distribution between the groups (p > 0.05). Four weeks following two different training protocols virtual reality distraction group shows more significant changes in pain intensity, FVC, FEV1, FEV1/FVC, PEF, RV, FRC, TLC, RV/TLC, and DLCO (p = 0.001) but not in RV (p = 0.541). The similar improvements were noted in the 8 weeks and 6 months follow up. The reports of the study concluded that virtual reality distraction is an effective and useful technique in reducing pain and increasing lung capacity in chest burn patient with ARDS following smoke inhalation in community-dwelling middle-aged adults. In the virtual reality distraction group, the patients reported significantly less pain and clinically meaningful changes in pulmonary functions as compared to the control group (physiotherapy + relaxation). • Analysis the effects of Virtual reality distraction technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in community-dwelling middle-aged adults. • Analysis the effects of Progressive muscle relaxation technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in community-dwelling middle-aged adults. • Compare the effects of Virtual reality distraction and Progressive muscle relaxation technique to improve chest burns with acute respiratory distress syndrome (ARDS) following smoke inhalation in community-dwelling middle-aged adults. [ABSTRACT FROM AUTHOR]

[Display omitted] Pulmonary fibrosis is a major cause of the poor prognosis of acute respiratory distress syndrome (ARDS). While mechanical ventilation (MV) is an indispensable life-saving intervention for ARDS, it may cause the remodeling process in lung epithelial cells to become disorganized and exacerbate ARDS-associated pulmonary fibrosis. Piezo1 is a mechanosensitive ion channel that is known to play a role in regulating diverse physiological processes, but whether Piezo1 is necessary for MV-exacerbated ARDS-associated pulmonary fibrosis remains unknown. This study aimed to explore the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. Human lung epithelial cells were stimulated with hydrochloric acid (HCl) followed by mechanical stretch for 48 h. A two-hit model of MV after acid aspiration-induced lung injury in mice was used. Mice were sacrificed after 14 days of MV. Pharmacological inhibition and knockout of Piezo1 were used to delineate the role of Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis. In some experiments, ATP or the ATP-hydrolyzing enzyme apyrase was administered. The stimulation of human lung epithelial cells to HCl resulted in phenotypes of epithelial-mesenchymal transition (EMT), which were enhanced by mechanical stretching. MV exacerbated pulmonary fibrosis in mice exposed to HCl. Pharmacological inhibition or knockout of Piezo1 attenuated the MV-exacerbated EMT process and lung fibrosis in vivo and in vitro. Mechanistically, the observed effects were mediated by Piezo1-dependent Ca2+ influx and ATP release in lung epithelial cells. Our findings identify a key role for Piezo1 in MV-exacerbated ARDS-associated pulmonary fibrosis that is mediated by increased ATP release in lung epithelial cells. Inhibiting Piezo1 may constitute a novel strategy for the treatment of MV-exacerbated ARDS-associated pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

• Duration from onset to the crisis is significantly shorter in TMG patients. • The in-hospital clinical outcome of MC is worse in TMG patients compared with that in non-thymoma-associated MG patients. • MG patients with unresected thymoma had longer hospital stays than that with POMC. Thymoma-associated myasthenia gravis (TMG) had more severe symptoms and worse prognoses in comparison to non-thymoma-associated MG. Thymoma recurrence was frequently associated with transient worsening of MG and even acute respiratory failure, namely myasthenic crisis (MC). However, little is known about the clinical features and outcomes of MC in thymoma-associated MG patients. We performed a retrospective cohort study in MG patients recruited from 9 independent tertiary neuromuscular centers in China from Jan 2015, through Oct 2022. Overall, 156 MC from 149 MG patients with positive anti-acetylcholine receptor (AChR) antibodies were finally analyzed. Next, these patients were divided into two subgroups: the TMG group (n = 60 MCs, 58 patients) and the non-thymoma-associated MG group (n = 96 MCs, 91 patients). Compared with non-thymoma-associated MG, TMG patients had a significantly shorter disease duration from symptom onset to the crisis (17.95±40.9 vs 51.31±60.61 months, P <0.0001), a larger proportion of MGFA IVa as the initial onset clinical classification (6.67% vs 0, P = 0.0205), and a longer hospital stay (39.24±22.09 [6–111] vs. 33.2 ± 23.42 days [7–120]; P = 0.0317) during the crisis. Within the TMG group, the hospital stay was significantly longer in patients with unresected thymoma compared to that in postoperative myasthenic crisis (POMC) (47.68±24.9 [6–111] vs. 34.21±18.87 days [12–82]; P = 0.0257). Early identification of the MG categories may provide some hints in tailoring therapeutic strategies to improve the prognosis. [ABSTRACT FROM AUTHOR]

This consensus aims to provide evidence-based recommendations on common questions in the diagnosis and treatment of acute respiratory failure (ARF) for critically ill cancer patients. We developed six clinical questions using the PICO (Population, Intervention, Comparison, and Outcome) principle in diagnosis and treatment for critical ill cancer patients with ARF. Based on literature searching and meta-analyses, recommendations were devised. The GRADE (Grading of Recommendation Assessment, Development and Evaluation) method was applied to each question to reach consensus in the expert panel. The panel makes strong recommendations in favor of (1) metagenomic next-generation sequencing (mNGS) tests may aid clinicians in rapid diagnosis in critically ill cancer patients suspected of pulmonary infections; (2) extracorporeal membrane oxygenation (ECMO) therapy should not be used as a routine rescue therapy for acute respiratory distress syndrome in critically ill cancer patients but may benefit highly selected patients after multi-disciplinary consultations; (3) cancer patients who have received immune checkpoint inhibitor therapy have an increased incidence of pneumonitis compared with standard chemotherapy; (4) critically ill cancer patients who are on invasive mechanical ventilation and estimated to be extubated after 14 days may benefit from early tracheotomy; and (5) high-flow nasal oxygen and noninvasive ventilation therapy can be used as a first-line oxygen strategy for critically ill cancer patients with ARFs. A weak recommendation is: (6) for critically ill cancer patients with ARF caused by tumor compression, urgent chemotherapy may be considered as a rescue therapy only in patients determined to be potentially sensitive to the anticancer therapy after multidisciplinary consultations. The recommendations based on the available evidence can guide diagnosis and treatment in critically ill cancer patients with acute respiratory failure and improve outcomes. [ABSTRACT FROM AUTHOR]

Thoracic spinal deformities may reduce chest wall compliance, leading to respiratory complications. The first SARS-CoV-2 (L-variant) strain caused critical respiratory illness, especially in vulnerable patients. This study investigates the association between scoliosis and SARS-CoV-2 (COVID-19) disease course severity. Clinical data of 129 patients treated between March 2020 to June 2021 who received a positive COVID-19 polymerase chain reaction result from Mount Sinai and had a scoliosis ICD-10 code (M41.0–M41.9) was retrospectively analyzed. Degree of coronal plane scoliosis on imaging was confirmed by 2 independent measurers and grouped into no scoliosis (Cobb angle <10°), mild (10°–24°), moderate (25°–39°), and severe (>40°) cohorts. Baseline characteristics were compared, and a multivariable logistic regression controlling for clinically significant comorbidities examined the significance of scoliosis as an independent risk factor for hospitalization, intensive care unit (ICU) admission, acute respiratory distress syndrome (ARDS), mechanical ventilation, and mortality. The no (n = 42), mild (n = 14), moderate (n = 44), and severe scoliosis (n = 29) cohorts differed significantly only in age (P = 0.026). The percentage of patients hospitalized (P = 0.59), admitted to the ICU (P = 0.33), developing ARDS (P = 0.77), requiring mechanical ventilation (P = 1.0), or who expired (P = 0.77) did not significantly differ between cohorts. The scoliosis cohorts did not have a significantly higher likelihood of hospital admission (mild P = 0.19, moderate P = 0.67, severe P = 0.98), ICU admission (P = 0.97, P = 0.94, P = 0.22), ARDS (P = 0.87, P = 0.74, P = 0.94), mechanical ventilation (P = 0.73, P = 0.69, P = 0.70), or mortality (P = 0.74, P = 0.87, P = 0.66) than the no scoliosis cohort. Scoliosis was not an independent risk factor for critical COVID-19 illness. No trends indicated any consistent effect of degree of scoliosis on increased adverse outcome likelihood. [ABSTRACT FROM AUTHOR]

• The ethanolic extract was prepared from the leaves of P. insignis. • GC-MS analysis performed on the ethanolic extract of P. insignis leaves revealed the presence of 60 phytocompounds. • HPLC analysis identified the flavonoid catechin which justifies the anti-inflammatory effect of P. insignis in the treatment of acute respiratory distress syndrome. Platonia insignis Mart., popularly known as bacuri, is a plant in which all its parts are indicated for use in folk medicine. The decoction of the seeds, for example, is used to treat diarrhea, while the oil from the seeds is used to treat skin diseases, otitis, rheumatism, arthritis, and cicatrization. The objective of this work was to perform a phytochemical analysis of the ethanolic extract of P. insignis leaves and to evaluate the pharmacological action of the extract on acute respiratory distress syndrome (ARDS) by intestinal ischemia and reperfusion in rats. For the induction of ARDS, male rats were distributed into seven groups. The negative control group was submitted to ischemia and reperfusion but was not treated. The test groups were treated by inhalation with ethanolic extract of freeze-dried P. insignis leaves (500 mg/kg) and associations. Lung structural and inflammatory changes were evaluated by histological examination. The preliminary phytochemical screening found that the leaf extract contained alkaloids, saponins, and triterpenes. The GCMS– analysis verified that the extract presented 60 compounds, in which phytol (10.54%), gamma-sitosterol (9.88%), and hexadecanoic acid (9.84%) were the major compounds identified. Analysis by CLAE revealed the secondary metabolite catechin in the extract. Finally, the extract was able to stagnate the marked dilation of terminal and respiratory bronchioles and alveoli. The results suggest that the ethanolic extract of P. insignis leaves is a promising therapeutic option to treat ARDS. [ABSTRACT FROM AUTHOR]

Tuberculosis can cause acute respiratory failure, which is associated with a high mortality rate, even in patients receiving effective anti-tuberculosis therapy. We retrospectively analyzed patients with acute respiratory failure associated with tuberculosis who underwent pulse steroid therapy to describe the clinical characteristics and effectiveness of pulse steroid therapy in this condition. The medical records of patients admitted to our hospital for culture-proven tuberculosis treatment from April 1, 2017, to March 31, 2022, who received pulse steroid therapy for acute respiratory failure associated with tuberculosis were reviewed. In total, 10 patients were included in this study. Chest computed tomography (CT) revealed diffuse ground-glass opacities and consolidation in these patients. Overall, 70% of the patients (7/10) showed an adjudicated response to pulse steroid therapy, with improved respiratory condition and radiological findings. Three patients died without response to pulse steroid therapy. One patient died of pancreatic cancer after recovering from respiratory failure. The remaining six patients were discharged without supplemental oxygen and completed anti-tuberculosis therapy. Pulse steroid therapy can lead to dramatic improvements in some patients with acute respiratory failure associated with tuberculosis. [ABSTRACT FROM AUTHOR]

Interest in cell-based therapy using extracellular vesicles (EVs) is intensifying, building upon promising preclinical research and a handful of published clinical studies. Registered clinical trials remain small, heterogeneous in design and underpowered to determine safety and efficacy on their own. A scoping review of registered studies can identify opportunities to pool data and perform meta-analysis. Registered trials were identified by searching clinical trial databases (Clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform and the Chinese Clinical Trial Registry) on June 10, 2022. Seventy-three trials were identified and included for analysis. Mesenchymal stromal cells (MSCs) were the most common cell type from which EVs were derived (49 studies, 67%). Among the 49 identified MSC-EV studies, 25 were controlled trials (51%) with a combined total of 3094 participants anticipated to receive MSC-derived EVs (2225 in controlled studies). Although EVs are being administered to treat a broad range of conditions, trials treating patients with coronavirus disease-2019 and/or acute respiratory distress syndrome were observed most commonly. Despite heterogeneity between studies, we anticipate that at least some of the studies could be combined in meaningful meta-analysis and that a combined sample size of 1000 patients would provide the ability to detect a ≥5% difference in mortality with MSC-EVs compared to controls and could be achieved by December 2023. This scoping review identifies potential barriers that may stall clinical translation of EV-based treatment, and our analysis calls for more standardized product characterization, use of quantifiable product quality attributes and consistent outcome reporting in future clinical trials. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 induces the expression of innate immune genes in the nasopharynx. • Expression of immune genes in the nasopharynx was associated with COVID-19 severity. • High plasminogen activator urokinase receptor and low chemokine C-X-C motif ligand 10 expression levels were related to COVID-19 pneumonia. • Low expression of interferon-stimulated gene 15, retinoic acid-inducible gene I, C-C motif ligand 5, and chemokine C-X-C motif ligand 10 was related to severe pneumonia. We analyzed the expression of inflammatory and antiviral genes in the nasopharynx of SARS-CoV-2 infected patients and their association with the severity of COVID-19 pneumonia. We conducted a cross-sectional study on 223 SARS-CoV-2 infected patients. Clinical data were collected from medical records, and nasopharyngeal samples were collected in the first 24 hours after admission to the emergency room. The gene expression of eight proinflammatory/antiviral genes (plasminogen activator urokinase receptor [ PLAUR ], interleukin [ IL ] -6, IL-8 , interferon [ IFN ] -β , IFN-stimulated gene 15 [ ISG15 ], retinoic acid-inducible gene I [ RIG-I ], C-C motif ligand 5 [ CCL5 ], and chemokine C-X-C motif ligand 10 [ CXCL10 ]) were quantified by real-time polymerase chain reaction. Outcome variables were: (i) pneumonia; (ii) severe pneumonia or acute respiratory distress syndrome. Statistical analysis was performed using multivariate logistic regression analyses. We enrolled 84 mild, 88 moderate, and 51 severe/critical cases. High expression of PLAUR (adjusted odds ratio [aOR] = 1.25; P = 0.032, risk factor) and low expression of CXCL10 (aOR = 0.89; P = 0.048, protective factor) were associated with pneumonia. Furthermore, lower values of ISG15 (aOR = 0.88, P = 0.021), RIG-I (aOR = 0.87, P = 0.034), CCL5 (aOR = 0.73, P <0.001), and CXCL10 (aOR = 0.84, P = 0.002) were risk factors for severe pneumonia/acute respiratory distress syndrome. An unbalanced early innate immune response to SARS-CoV-2 in the nasopharynx, characterized by high expression of PLAUR and low expression of antiviral genes (ISG15 and RIG-I), and chemokines (CCL5 and CXCL10), was associated with COVID-19 severity. [Display omitted] [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia (HTG) is a major cause of acute pancreatitis (AP). We aimed to determine whether HTG is an independent risk factor for AP complications and construct a prediction model for non-mild AP. We conducted a multi-center cohort study including 872 patients with AP and divided them into HTG-AP and non-HTG-AP groups. Multivariate logistic regression was performed, and a prediction model for non-mild HTG-AP was developed. HTG-AP patients had a higher risk of systemic complications, including systemic inflammatory response syndrome [odds ratio (OR): 1.718; 95% confidence interval (CI): 1.286–2.295], shock (OR: 2.103; 95%CI: 1.236–3.578), acute respiratory distress syndrome (OR: 2.231; 95%CI: 1.555–3.200), acute renal failure (OR: 1.593; 95%CI: 1.036–2.450), and local complications such as acute peripancreatic fluid collection (OR: 2.072; 95%CI: 1.550–2.771), acute necrotic collection (OR: 1.996; 95%CI: 1.394–2.856), and walled-off necrosis (OR: 2.157; 95%CI: 1.202–3.870). The area under curve of our prediction model was 0.898 (95%CI: 0.857–0.940) and 0.875 (95%CI: 0.804–0.946) in the derivation and validation datasets respectively. HTG is an independent risk factor for AP complications. We constructed a simple and accurate prediction model for progression of non-mild AP. [ABSTRACT FROM AUTHOR]