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Post intensive care syndrome (PICS) affects an increasing number of critical illness survivors and their families, with serious physical and psychological sequelae. Since little is known about the burden of critical illness on ICU survivor families, we conducted a prospective observational study aiming to assess this, and investigate correlations of the patients’ psychometric and health-related quality of life (HRQOL) scores with family burden.

Chrysi Keskinidou, Alice G Vassiliou, Ioanna Dimopoulou, Anastasia Kotanidou, Stylianos E Orfanos First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, “Evangelismos” Hospital, Athens, GreeceCorrespondence: Alice G Vassiliou; Stylianos E Orfanos, First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, “Evangelismos” Hospital, Athens, Greece, Tel +30 210 7235521, Fax +30 210 7239127, Email alvass75@gmail.com; stylianosorfanosuoa@gmail.comAbstract: Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury characterized by an acute inflammatory response in the lung parenchyma. Hence, it is considered as the most appropriate clinical syndrome to study pathogenic mechanisms of lung inflammation. ARDS is associated with increased morbidity and mortality in the intensive care unit (ICU), while no effective pharmacological treatment exists. It is very important therefore to fully characterize the underlying pathobiology and the related mechanisms, in order to develop novel therapeutic approaches. In vivo and in vitro models are important pre-clinical tools in biological and medical research in the mechanistic and pathological understanding of the majority of diseases. In this review, we will present data from selected experimental models of lung injury/acute lung inflammation, which have been based on clinical disorders that can lead to the development of ARDS and related inflammatory lung processes in humans, including ventilation-induced lung injury (VILI), sepsis, ischemia/reperfusion, smoke, acid aspiration, radiation, transfusion-related acute lung injury (TRALI), influenza, Streptococcus (S.) pneumoniae and coronaviruses infection. Data from the corresponding clinical conditions will also be presented. The mechanisms related to lung inflammation that will be covered are oxidative stress, neutrophil extracellular traps, mitogen-activated protein kinase (MAPK) pathways, surfactant, and water and ion channels. Finally, we will present a brief overview of emerging techniques in the field of omics research that have been applied to ARDS research, encompassing genomics, transcriptomics, proteomics, and metabolomics, which may recognize factors to help stratify ICU patients at risk, predict their prognosis, and possibly, serve as more specific therapeutic targets.Keywords: acute respiratory distress syndrome, lung inflammation, mechanisms, biomarkers, omics

A potential complication in critically ill patients is the formation of bone in soft tissues, termed heterotopic ossification. The exact pathogenetic mechanisms are still undetermined. Bone morphogenetic proteins induce bone formation, while signalling through the receptor activator of nuclear factor kappa-Β (RANK) and its ligand (RANKL), regulates osteoclast formation, activation, and survival in normal bone modelling and remodelling. Osteoprotegerin protects bone from excessive bone loss by blocking RANKL from binding to RANK.

Healthcare professionals who are directly involved in the diagnosis, treatment, and general care of patients with SARS-CoV-2 are at risk of developing adverse psychological reactions. A cross-sectional study of healthcare professionals aimed to determine the impact of the SARS-CoV-2 pandemic on the mental health of healthcare professionals in two of the largest referral hospitals in Athens, Greece.

BACKGROUND: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. METHODS: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). FINDINGS: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61-1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64-1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09-0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. INTERPRETATION: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. FUNDING: Hellenic Foundation for Research and Innovation.

Purpose There is growing interest in improving the inclusiveness of racial and ethnic minority participants in trials of acute respiratory distress syndrome (ARDS). With our study we aimed to examine temporal trends of representation and mortality of racial and ethnic minority participants in randomized controlled trials of ARDS. Methods We performed a secondary analysis of eight ARDS Network and PETAL Network therapeutic clinical trials, published between 2000 and 2019. We classified race/ethnicity into 'White', 'Black', 'Hispanic', or 'Other' (including Asian, American Indian or Alaskan Native, Native Hawaiian, or other Pacific Islander participants). Results Of 5375 participants with ARDS, 1634 (30.4%) were Black, Hispanic, or Other race participants. Representation of racial and ethnic minority participants in trials did not change significantly over time (p = 0.257). However, among participants with moderate to severe ARDS (i.e., partial pressure of arterial oxygen to fraction of inspired oxygen ratio < 150), the difference in mortality between racial and ethnic minority participants and White participants decreased over time. In the five most recent trials, including 2923 participants with ARDS, there were no statistically significant differences in mortality between racial/ethnic groups, even after adjusting for potential confounders. In these five most recent trials, mortality was 31% for White, 31.9% for Black, 30.3% for Hispanic, and 37.1% for Other race participants (p = 0.633). Conclusion Representation of racial and ethnic minority participants in ARDS trials from North America, published between 2000 and 2019, did not change over time. Black and Hispanic participants with ARDS may have similar mortality as White participants within trials., Author(s): Eleni Papoutsi [sup.1], Panagiotis Kremmydas [sup.1], Vasiliki Tsolaki [sup.2], Anna Kyriakoudi [sup.3], Christina Routsi [sup.1], Anastasia Kotanidou [sup.1], Ilias I. Siempos [sup.1] [sup.4] Author Affiliations: (1) First Department of [...]

Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines. Data are limited regarding the optimal antimicrobial duration in HAP patients, and it should be individually tailored to each patient, taking into account the causative pathogen and the clinical response. Shorter courses are found to be as effective as longer courses in the management of VAP, except for pneumonia caused by non-fermenting Gram-negative bacteria; however, duration should be balanced between the possibility of higher recurrence rates and the documented benefits with shorter courses. Additionally, the validation of reliable biomarkers or clinical predictors that identify patients who would benefit from shorter therapy is crucial. Insights from this review may lead to future research on personalized antimicrobial therapies in pneumonia, in order to improve patient outcomes.

Background/objectives: Blood culture (BC) contamination is a frequent problem which leads to increased laboratory workload, inappropriate use of antibiotics and the associated adverse events, and increased healthcare costs. This study prospectively examined the effect of a care bundle on BC contamination rates in a high workload ICU. Results: During the study, in total, 4236 BC vials were collected. After the intervention, the BC contamination rate decreased significantly from 6.2% to 1.3%. The incidence rate of contaminated BC sets was significantly lower following the intervention: 0.461 vs. 0.154 BC sets per 100 ICU bed-days. Overall compliance with the BC care bundle increased dramatically from 3.4% to 96.9%. Methods: We performed a before–after study in a general ICU from January 2018 to May 2019, with the intervention starting on November 2018. Blood culture sets were classified as positive, contaminated, indeterminate, and negative. We used bivariate and interrupted time series analysis to assess the effect of the intervention on BC contamination rates and other BC quality indicators. Conclusions: The BC care bundle was effective in reducing BC contamination rates and improving several quality indicators in our setting. The indeterminate BC rate is an important but understudied problem, and we suggest that it should be included in BC quality indicators as well. A significant limitation of the study was that the long-term effect of the intervention was not assessed.

Background: Adolescent overweight and obesity are a public health problem with an epidemic trend. There is growing evidence that sleep quality correlates to body weight. The aim of this study was to investigate, sleep quality in adolescents with obesity/overweight. Methods: A total of 100 adolescents with overweight/obesity aged 12–18 years were enrolled. Anthropometric parameters were recorded and a laboratory investigation in the fasting state [glucose, insulin, cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, uric acid and glycated hemoglobin (HbA1c)] was performed. Insulin resistance was calculated by the Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR). Sleep quality was assessed with the Adolescent Sleep Hygiene Scale (ASHS) questionnaire. Results: According to ASHS, 93% of the participants were classified as “Good Sleepers” (GSs) (score > 3.8) and 7% as “Poor Sleepers” (PSs) (score < 3.8). PSs had a statistically higher body mass index (BMI) compared to GSs (p = 0.026). Increased body mass index (BMI) (r = −0.306, p = 0.002), fast insulin (r = −0.224, p = 0.027), and HOMA-IR (r = −0.260, p = 0.010) exerted a negative effect on sleep quality. Controlling for lipids and uric acid, only TC levels appeared to have a statistically significant and specifically positive correlation with the ASHS score (r = 0.202, p = 0.045). HbA1c values and waist circumference tended to be negatively correlated, but not significant to adolescent sleep quality [(r = −0.101, p = 0.330), (r = −0.095, p = 0.359), respectively]. The influence of central obesity on the ASHS score was also explored, but no correlation was found (p = 0.566). Conclusions: Sleep quality, as reflected by the ASHS score, was associated negatively with BMI, fasting insulin levels, and insulin resistance. Furthermore, a gender difference was observed, as adolescent males were found to achieve a higher overall ASHS score compared to females.

Background: Cervical ectopic pregnancy is a relatively rare type of ectopic pregnancy and has no standardized guidelines for management.Methods: This systematic review is based on the collection of case reports, published in PubMed/MEDLINE about the resolution of ectopic cervical pregnancies over the last decade and the presentation of a case managed in our healthcare unit. Studies involving cervical pregnancy in the first trimester with the presence of a viable embryo and β-hCG in the serum below 100.000 mIU/mL were included, while heterotopic pregnancies were excluded.Results: Nineteen articles reporting twenty-three case reports are demonstrated explicitly emphasizing on the management techniques. There is no established approach for the management of this type of ectopic pregnancy.Conclusion: It is important to consider the conservative approaches as first-line treatment in all cases of cervical pregnancy preserving fertility. Minimally invasive methods are also described and preferred as second-line treatment, as reported in our literature review.

Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (n = 40) and Balb/c (n = 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (RN), tissue damping (G) and elastance coefficient (H), hysteresivity (η), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly during the first months of 2020 and continues to expand in multiple areas across the globe. Molecular epidemiology has provided an added value to traditional public health tools by identifying SARS-CoV-2 clusters or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to estimate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 full-genome SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in five replicates of 3,000 sequences sampled globally, as well as the best hits to our data set identified by BLAST. Phylogenetic trees were reconstructed by the maximum likelihood method, and the putative source of SARS-CoV-2 infections was inferred by phylogeographic analysis. Phylogenetic analyses revealed the presence of 89 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on thorough risk assessment), respectively. The results of phylogeographic analysis were confirmed by a Bayesian approach. Our findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic. IMPORTANCE Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic. Our results can provide a roadmap about prevention policy in the future regarding the reopening of borders in the presence of differences in vaccination coverage, the circulation of the virus, and the presence of newly emergent variants across the globe.

Abstract Background Differential diagnosis of patients with lung infiltrates remains a challenge. Triggering receptor expressed on myeloid cells (TREM)-1 is a neutrophil and monocyte receptor up-regulated during infection. The aim of this study was to evaluate the diagnostic accuracy of TREM-1 and of C-reactive protein (CRP) from patients with lung infiltrates to discern community acquired lung infections. Methods 68 patients admitted to a medical ward with acute respiratory illness were enrolled in the study. Neutrophil and monocyte TREM-1 expression were measured by flow cytometry, sTREM-1 by an enzyme immunoassay and C-reactive protein by nephelometry. Clinical pulmonary infection score was recorded. Results 34 patients were diagnosed with bacterial community acquired pneumonia (group A) and 34 with non-bacterial pulmonary disease (group B). Median serum TREM-1 concentration was 102.09 pg/ml in group A and lower than 15.10 pg/ml (p < 0.0001) in group B. Mean±SE neutrophil TREM-1 expression was 4.67 ± 0.53 MFI in group A and 2.64 ± 0.25 MFI (p = 0.001) in group B. Monocyte TREM-1 expression was 4.2 ± 0.42 MFI in group A and 2.64 ± 0.35 MFI (p = 0.007) in group B and mean±SE CRP was 18.03 ± 2 mg/ml in group A and 7.1 ± 1.54 mg/ml (p < 0.001) in group B. A cut-off of 19.53 pg/ml of sTREM-1 with sensitivity 82.6% and specificity 63% to discriminate between infectious and non-infectious pulmonary infiltrates was found. sTREM-1 at admission greater than 180 pg/ml was accompanied with unfavourable outcome. Conclusion TREM-1 myeloid expression and sTREM-1 are reliable markers of bacterial infection among patients with pulmonary infiltrates; sTREM-1 is a predictor of final outcome.

Appendiceal neoplasms are usually asymptomatic or associated with mild, nonspecific symptoms. Due to the rarity of the disease and the lack of specific symptoms, this clinical entity escapes the diagnostic consideration of the gynecologist, when women come in with right iliac fossa pain. A case is presented of a 56‐year‐old woman with a mass in the right small pelvis, which was preoperatively diagnosed as originating from the ovary. An exploratory laparotomy followed in which the uterus and appendages were found to be macroscopically normal, while the mass described above came from the appendix, extended into the anatomical area of the right accessory, and was in contact with the atrophic right ovary. The appendix vermiformis was removed intact. The final pathologic examination confirmed an acellular mucinous tumor of the appendix. Accurate preoperative diagnosis of mucoceles is extremely difficult to make. The formation is discovered in a random imaging test, and the diagnosis is confirmed only intraoperatively. [ABSTRACT FROM AUTHOR]

Rationale: Because of the effects of aging on the respiratory system, it is conceivable that the association between driving pressure and mortality depends on age. Objectives: We endeavored to evaluate whether the association between driving pressure and mortality of patients with acute respiratory distress syndrome (ARDS) varies across the adult lifespan, hypothesizing that it is stronger in older, including very old (⩾80 yr), patients. Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials ("ARDSNet cohort"). We tested our hypothesis in a second, independent, national cohort ("Hellenic cohort"). We performed both binary logistic and Cox regression analyses including the interaction term between age (as a continuous variable) and driving pressure at baseline (i.e., the day of trial enrollment) as the predictor and 90-day mortality as the dependent variable. Measurements and Main Results: On the basis of data from 4,567 patients with ARDS included in the ARDSNet cohort, we found that the effect of driving pressure on mortality depended on age (P = 0.01 for the interaction between age as a continuous variable and driving pressure). The difference in driving pressure between survivors and nonsurvivors significantly changed across the adult lifespan (P < 0.01). In both cohorts, a driving pressure threshold of 11 cm H2O was associated with mortality in very old patients. Conclusions: Data from randomized controlled trials with strict inclusion criteria suggest that the effect of driving pressure on the mortality of patients with ARDS may depend on age. These results may advocate for a personalized age-dependent mechanical ventilation approach. [ABSTRACT FROM AUTHOR]

Pneumonia remains a major global health concern, causing significant morbidity and mortality among adults. This narrative review assesses the optimal duration of antimicrobial treatment in adults with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). Current evidence about the impact of treatment duration on clinical outcomes demonstrates that shorter antibiotic courses are non-inferior, regarding safety and efficacy, compared to longer courses, particularly in patients with mild to moderate CAP, which is in line with the recommendations of international guidelines. Data are limited regarding the optimal antimicrobial duration in HAP patients, and it should be individually tailored to each patient, taking into account the causative pathogen and the clinical response. Shorter courses are found to be as effective as longer courses in the management of VAP, except for pneumonia caused by non-fermenting Gram-negative bacteria; however, duration should be balanced between the possibility of higher recurrence rates and the documented benefits with shorter courses. Additionally, the validation of reliable biomarkers or clinical predictors that identify patients who would benefit from shorter therapy is crucial. Insights from this review may lead to future research on personalized antimicrobial therapies in pneumonia, in order to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background/objectives: Blood culture (BC) contamination is a frequent problem which leads to increased laboratory workload, inappropriate use of antibiotics and the associated adverse events, and increased healthcare costs. This study prospectively examined the effect of a care bundle on BC contamination rates in a high workload ICU. Results: During the study, in total, 4236 BC vials were collected. After the intervention, the BC contamination rate decreased significantly from 6.2% to 1.3%. The incidence rate of contaminated BC sets was significantly lower following the intervention: 0.461 vs. 0.154 BC sets per 100 ICU bed-days. Overall compliance with the BC care bundle increased dramatically from 3.4% to 96.9%. Methods: We performed a before–after study in a general ICU from January 2018 to May 2019, with the intervention starting on November 2018. Blood culture sets were classified as positive, contaminated, indeterminate, and negative. We used bivariate and interrupted time series analysis to assess the effect of the intervention on BC contamination rates and other BC quality indicators. Conclusions: The BC care bundle was effective in reducing BC contamination rates and improving several quality indicators in our setting. The indeterminate BC rate is an important but understudied problem, and we suggest that it should be included in BC quality indicators as well. A significant limitation of the study was that the long-term effect of the intervention was not assessed. [ABSTRACT FROM AUTHOR]

Background/Objectives: Endometriosis is characterized by the presence of ectopic endometrial-like glands and stroma outside the endometrial cavity, which mainly occurs in the pelvic cavity. Pulmonary endometriosis, or thoracic endometriosis syndrome (TES), describes the rare presence of endometrial-like cells in the thoracic cavity and includes catamenial pneumothorax, catamenial hemothorax, hemoptysis, and lung nodules. Our aim is to summarize the results of all reported cases of TES. Methods: Extensive research was conducted through MEDLINE/PUBMED using the keywords "thoracic endometriosis", "thoracic endometriosis syndrome", "catamenial pneumothorax", "catamenial hemoptysis", and "TES". Following PRISMA guidelines, all published cases of TES between January 1950 and March 2024 were included. A systematic review of 202 studies in English, including 592 patients, was performed. Results: The median age of women with TES is 33.8 years old. The most common clinical presentation is catamenial pneumothorax (68.4%), while lesions are mainly found in the right lung unilaterally (79.9%). Chest computed tomography (CT) was used alone or after an X-ray to determine the pathological findings. Ground-glass opacity nodules and cystic lesions represent the most common finding in CT, while pneumothorax is the most common finding in X-rays. Video-assisted thoracoscopic surgery (VATS) is the main therapeutic approach, usually in combination with hormonal therapy, including GnRH analogues, progestins, androgens, or combined oral contraceptives. Hormonal therapy was also administered as monotherapy. Symptom recurrence was reported in 10.1% of all cases after the treatment. Conclusions: High clinical awareness and a multidisciplinary approach are necessary for the best clinical outcome for TES patients. More studies are required to extract safer conclusions. [ABSTRACT FROM AUTHOR]

Background: Adolescent overweight and obesity are a public health problem with an epidemic trend. There is growing evidence that sleep quality correlates to body weight. The aim of this study was to investigate, sleep quality in adolescents with obesity/overweight. Methods: A total of 100 adolescents with overweight/obesity aged 12–18 years were enrolled. Anthropometric parameters were recorded and a laboratory investigation in the fasting state [glucose, insulin, cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides, uric acid and glycated hemoglobin (HbA1c)] was performed. Insulin resistance was calculated by the Homeostasis Model Assessment of Insulin Resistance index (HOMA-IR). Sleep quality was assessed with the Adolescent Sleep Hygiene Scale (ASHS) questionnaire. Results: According to ASHS, 93% of the participants were classified as "Good Sleepers" (GSs) (score > 3.8) and 7% as "Poor Sleepers" (PSs) (score < 3.8). PSs had a statistically higher body mass index (BMI) compared to GSs (p = 0.026). Increased body mass index (BMI) (r = −0.306, p = 0.002), fast insulin (r = −0.224, p = 0.027), and HOMA-IR (r = −0.260, p = 0.010) exerted a negative effect on sleep quality. Controlling for lipids and uric acid, only TC levels appeared to have a statistically significant and specifically positive correlation with the ASHS score (r = 0.202, p = 0.045). HbA1c values and waist circumference tended to be negatively correlated, but not significant to adolescent sleep quality [(r = −0.101, p = 0.330), (r = −0.095, p = 0.359), respectively]. The influence of central obesity on the ASHS score was also explored, but no correlation was found (p = 0.566). Conclusions: Sleep quality, as reflected by the ASHS score, was associated negatively with BMI, fasting insulin levels, and insulin resistance. Furthermore, a gender difference was observed, as adolescent males were found to achieve a higher overall ASHS score compared to females. [ABSTRACT FROM AUTHOR]

Background Plitidepsin has shown potent preclinical activity against severe acute respiratory syndrome coronavirus 2 and was generally well tolerated in a phase I trial of hospitalized patients with coronavirus disease 2019 (COVID-19). NEPTUNO, a phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. Methods Included patients had documented severe acute respiratory syndrome coronavirus 2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. Results After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19–related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio, 1.37; 95% confidence interval,.96–1.96; P =.08 for plitidepsin 1.5 mg vs control; hazard ratio, 1.06; 95% confidence interval,.73–1.53; P =.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. Conclusions Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. Results from this phase III trial suggest that plitidepsin, a first-in-class antiviral, may have a positive benefit-risk ratio in the management of hospitalized patients requiring oxygen therapy for moderate COVID-19. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) is a potent vasoconstrictor produced by endothelial cells and cleared from circulating blood mainly in the pulmonary vasculature. In a healthy pulmonary circulation, the rate of local production of ET-1 is less than its rate of clearance. In the present study, we aimed to investigate whether the abnormal pulmonary circulatory handling of ET-1 relates to poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS). To this end, central venous and systemic arterial ET-1 plasma levels were simultaneously measured on Days 1 and 3 following ICU admission in mechanically ventilated COVID-19 patients with ARDS (COVID-19 ARDS, N = 18). Central venous and systemic arterial ET-1 plasma levels were also measured in two distinct SARS-CoV-2-negative mechanically ventilated critically ill patient groups, matched for age, sex, and critical illness severity, with ARDS (non-COVID-19 ARDS, N = 14) or without ARDS (non-COVID-19 non-ARDS, N = 20). Upon ICU admission, COVID-19-induced ARDS patients had higher systemic arterial and central venous ET-1 levels compared to the non-COVID-19 ARDS and non-COVID-19 non-ARDS patients (p < 0.05), yet a normal systemic arterial:central venous (A:V) ET-1 ratio [0.63 (0.49–1.02)], suggesting that pulmonary ET-1 clearance is intact in these patients. On the other hand, the non-COVID-19 ARDS patients demonstrated abnormal ET-1 handling [A:V ET-1 ratio 1.06 (0.93–1.20)], while the non-COVID-19 non-ARDS group showed normal ET-1 handling [0.79 (0.52–1.11)]. On Day 3, the A:V ratio in all three groups was <1. When the COVID-19 ARDS patients were divided based on 28-day ICU mortality, while their systemic arterial and central venous levels did not differ, the A:V ET-1 ratio was statistically significantly higher upon ICU admission in the non-survivors [0.95 (0.78–1.34)] compared to the survivors [0.57 (0.48–0.92), p = 0.027]. Our results highlight the potential importance of ET-1 as both a biomarker and a therapeutic target in critically ill COVID-19 patients. The elevated A:V ET-1 ratio in non-survivors suggests that the early disruption of pulmonary ET-1 handling may be a key marker of poor prognosis. [ABSTRACT FROM AUTHOR]