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Hypoxia is characterized as one of the main consequences of sepsis, which is recognized as the leading cause of death in intensive care unit (ICU) patients. In this study, we aimed to examine whether the expression levels of genes regulated under hypoxia could be utilized as novel biomarkers for sepsis prognosis in ICU patients. Whole blood expression levels of hypoxia-inducible factor-1α (HIF1A), interferon-stimulated gene 15 (ISG15), hexokinase 2 (HK2), lactate dehydrogenase (LDHA), heme oxygenase-1 (HMOX1), erythropoietin (EPO), and the vascular endothelial growth factor A (VEGFA) were measured on ICU admission in 46 critically ill, initially non-septic patients. The patients were subsequently divided into two groups, based on the development of sepsis and septic shock (n = 25) or lack thereof (n = 21). HMOX1 mRNA expression was increased in patients who developed sepsis/septic shock compared to the non-septic group (p < 0.0001). The ROC curve, multivariate logistic regression, and Kaplan–Meier analysis demonstrated that HMOX1 expression could be utilized for sepsis and septic shock development probability. Overall, our results indicate that HMOX1 mRNA levels have the potential to be a valuable predictive factor for the prognosis of sepsis and septic shock in ICU patients.

Abstract Background The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ventilator-induced lung injury (VILI). Autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular lysophosphatidic acid (LPA) production, has been suggested to play a pathogenic role in, among others, pulmonary inflammation and fibrosis. Methods C57BL/6 mice were subjected to low and high tidal volume mechanical ventilation using a small animal ventilator: respiratory mechanics were evaluated, and plasma and bronchoalveolar lavage fluid (BALF) samples were obtained. Total protein concentration was determined, and lung histopathology was further performed Results Injurious ventilation resulted in increased BALF levels of ATX. Genetic deletion of ATX from bronchial epithelial cells attenuated VILI-induced pulmonary edema. Conclusion ATX participates in VILI pathogenesis.

Abstract The Pulmonary Vascular Research Institute GoDeep meta‐registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta‐registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty‐nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface‐based automated retrospective and prospective data transfer, GoDeep aims to provide in‐depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management.

Abstract Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow–FCSA curves over a range of flows. We noted where the curves diverged from the theoretical line of pure recruitment (Recruitment) and determined the flow where the curve slope equalled 50% that of Recruitment, or equalled that of a theoretical curve representing full capillary distention (Distention). The three mammalian species have similar flow ranges for the transition from predominantly recruitment to predominantly distention, with dogs having the highest transition point. Within the physiological range of most daily activity, the species are similar and accommodate increasing blood flow mainly via recruitment, with progressive distention at higher flows. This is highly relevant to pulmonary physiology during exercise.

25-hydroxyvitamin D [25(OH)D] is an important immunomodulator, whose deficiency may aggravate the incidence and outcome of infectious complications in patients admitted to the intensive care unit. The most recognized extra-skeletal action of vitamin D is the regulation of immune function. Host defense against intracellular pathogens depends upon both innate and adaptive immunity. It has been suggested that vitamin D regulates the pro-inflammatory endothelial response to lipopolysaccharide, rendering it a role in the sepsis cascade. Recent studies have indicated that vitamin D deficiency may be associated with worse outcomes in patients with coronavirus disease 2019 (COVID-19), such as more severe disease and higher mortality rates. To this end, clinical trials with vitamin D supplementation are being carried out in an effort to improve COVID-19 outcomes. In this review, we will discuss the role of vitamin D in the immune response, and more specifically its effect on immune cells. Subsequently, we will provide an overview of the studies that have investigated the predictive value of vitamin D in critical illness outcomes, and its therapeutic value as a supplement in critically ill patients. Finally, the emerging role of vitamin D deficiency in COVID-19 infection risk, and worse outcomes will be discussed.

Acute Kidney Injury (AKI) commonly complicates cardiac surgery in children with congenital heart disease (CHD). In this study we assessed incidence, risk factors, and outcomes of postoperative AKI, while testing the hypothesis that, depending on the underlying diagnosis, there would be significant differences in AKI incidence among different diagnostic groups. We conducted an observational cohort study of children with CHD undergoing cardiac surgery in a single tertiary center between January 2019 and August 2021 (n = 362). Kidney Disease Improving Global Outcome (KDIGO) criteria were used to determine the incidence of postoperative AKI. Diagnosis was incorporated into multivariate models using an anatomic-based CHD classification system. Overall survival was estimated using Kaplan–Meier curves. Log-rank test and adjusted Cox proportional hazard modelling were used to test for differences in survival distributions and determine AKI effect on survival function, respectively. AKI occurred in 70 (19.3%), with 21.4% in-hospital mortality for AKI group. Younger age, lower weight, longer cardiopulmonary bypass time, preoperative mechanical ventilation and diagnostic category were associated with postoperative AKI. Resolution rate was 92.7% prior to hospital discharge for survivors. AKI was associated with longer duration of mechanical ventilation, ICU and hospital length of stay. AKI patients had significantly higher probability of all-cause mortality postoperatively when compared to the non-AKI group (log-rank test, p < 0.001). Adjusted hazard ratio for AKI versus non-AKI group was 11.08 (95% CI 2.45–50.01; p = 0.002). Diagnostic category was associated with cardiac surgery-related AKI in children with CHD, a finding supporting the development of lesion specific models for risk stratification. Postoperative AKI had detrimental impact on clinical outcomes and was associated with decreased survival to hospital discharge.

SARS-CoV-2 infection may result in severe pneumonia leading to mechanical ventilation and intensive care (ICU) treatment. Complement activation was verified in COVID-19 and implicated as a contributor to COVID-19 pathogenesis. This study assessed the predictive potential of complement factors C3a and C5b-9 for COVID-19 progression and outcome. We grouped 80 COVID-19 patients into severe COVID-19 patients (n = 38) and critically ill (n = 42) and subdivided into non-intubated (n = 48) and intubated (n = 32), survivors (n = 57) and non-survivors (n = 23). Results: A significant increase for C3a and C5b-9 levels was observed between: severely and critically ill patients (p < 0.001 and p < 0.0001), non-intubated vs intubated (p < 0.001 and p < 0.05), survivors vs non-survivors (p < 0.001 and p < 0.01). ROC analysis for the need for ICU treatment revealed a higher AUC for C5b-9 (0.764, p < 0.001) compared to C3a (AUC = 0.739, p < 0.01). A higher AUC was observed for C3a for the need for intubation (AUC = 0.722, p < 0.001) or mortality (AUC = 0.740, p < 0.0001) compared to C5b-9 (need for intubation AUC = 0.656, p < 0.05 and mortality AUC = 0.631, p = NS). Combining the two markers revealed a powerful prediction tool for ICU admission (AUC = 0.773, p < 0.0001), intubation (AUC = 0.756, p < 0.0001) and mortality (AUC = 0.753, p < 0.001). C3a and C5b-9 may be considered as prognostic tools separately or in combination for the progression and outcome of COVID-19.

Pulmonary hypertension (PH) development remains a significant cardiovascular complication of haemoglobinopathies, severely affecting the morbidity and mortality of such patients. According to the 5th World Symposium on PH, PH related with chronic haemolytic anaemias is classified in group 5, mainly due to the multifactorial pathophysiology of PH in this patient population. There are no clear guidelines regarding the management of PH in patients with haemoglobinopathies; the use of specific pulmonary arterial hypertension (PAH) therapy in patients with β-thalassaemia and PH is based on data derived from other forms of PH, expert opinion and small series or case reports. The existing knowledge on the use of specific-PAH therapy in β-thalassaemia patients with PH is limited, and in most cases the diagnosis of PH is based on echocardiographic findings only. We herein report two patients with β-thalassaemia intermedia (TI) and PH, who got same initial approach but different outcome, to highlight the wide spectrum of TI-induced PH, the importance of optimal disease-directed therapy and the possible role of specific-PAH therapy. We also emphasize the central role of right heart catheterization in the diagnosis and follow-up of PH, since this information does facilitate the suitable use or withdrawal of specific PAH drugs in these patients.

Heme-oxygenase (HO)-1 is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties and previous reports have also emphasized the antiviral properties of HO-1, either directly or via induction of interferons. To investigate the potential role of HO-1 in patients with coronavirus disease 2019 (COVID-19), the present study assessed changes in HO-1 expression in whole blood and tissue samples. Upregulation of HO-1 protein was observed in lung, liver, and skin tissue independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence. A significant increase of blood HO-1 mRNA levels was observed in critically ill COVID-19 patients compared to those in severe COVID-19 patients and healthy controls. This increase was accompanied by significantly elevated levels of serum ferritin and bilirubin in critically ill compared to patients with severe disease. Further grouping of patients in survivors and non-survivors revealed a significant increase of blood HO-1 mRNA levels in the later. Receiver operating characteristic (ROC) analysis for prediction of ICU admission and mortality yielded an AUC of 0.705 (p = 0.016) and 0.789 (p = 0.007) respectively indicating that HO-1 increase is associated with poor COVID-19 progression and outcome. The increase in HO-1 expression observed in critically ill COVID-19 patients could serve as a mechanism to counteract increased heme levels driving coagulation and thrombosis or as an induced protective mechanism.

In the last years, biomarkers of infection, such as the soluble urokinase plasminogen activator receptor (suPAR), have been extensively studied as potential diagnostic and prognostic biomarkers in the intensive care unit (ICU). In this study, we investigated whether this biomarker can be used in COVID-19 and non-COVID-19 septic patients for mortality prediction. Serum suPAR levels were measured in 79 non-COVID-19 critically ill patients upon sepsis (within 6 h), and on admission in 95 COVID-19 patients (66 critical and 29 moderate/severe). The non-COVID-19 septic patients were matched for age, sex, and disease severity, while the site of infection was the respiratory system. On admission, COVID-19 patients presented with higher suPAR levels, compared to non-COVID-19 septic patients (p < 0.01). More importantly, suPAR measured upon sepsis could not differentiate survivors from non-survivors (p > 0.05), as opposed to suPAR measured on admission in COVID-19 survivors and non-survivors (p < 0.0001). By the generated ROC curve, the prognostic value of suPAR in COVID-19 was 0.81, at a cut-off value of 6.3 ng/mL (p < 0.0001). suPAR measured early (within 24 h) after hospital admission seems like a specific and sensitive mortality risk predictor in COVID-19 patients. On the contrary, suPAR measured at sepsis diagnosis in non-COVID-19 critically ill patients, does not seem to be a prognostic factor of mortality.

Current achievements in medical science and technological advancements in intensive care medicine have allowed better support of critically ill patients in intensive care units (ICUs) and have increased survival probability. Post-intensive care syndrome (PICS) is a relatively new term introduced almost 10 years ago, defined as “new or worsening impairments in physical, cognitive, or mental health status arising after critical illness and persisting beyond acute care hospitalization”. A significant percentage of critically ill patients suffer from PICS for a prolonged period of time, with physical problems being the most common. The exact prevalence of PICS is unknown, and many risk factors have been described well. Coronavirus disease 2019 (COVID-19) survivors seem to be at especially high risk for developing PICS. The families of ICU survivors can also be affected as a response to the stress suffered during the critical illness of their kin. This separate entity is described as PICS family (PICS-F). A multidisciplinary approach is warranted for the treatment of PICS, involving healthcare professionals, clinicians, and scientists from different areas. Improving outcomes is both challenging and imperative for the critical care community. The review of the relevant literature and the study of the physical, cognitive, and mental sequelae could lead to the prevention and timely management of PICS and the subsequent improvement of the quality of life for ICU survivors.

The present cross-sectional study consists of a comprehensive analysis of epidemiological, laboratory, and clinical characteristics of COVID-19 patients in relation to their immunogenetic profiles. We studied 125 COVID-19 patients comprising different stages of disease severity; non-hospitalized (mild n = 69) and hospitalized (n = 56). Analysis of disease characteristics revealed no major differences between males and females of each group of patients while hospitalized patients were older and presented with comorbidities. A positive allele association was observed for HLA-DRB1*01 in total COVID-19 patients versus healthy controls. Subgrouping of COVID-19 patients in mild and hospitalized further identified a statistically significant increase in HLA-DRB1*01 in mild COVID-19 patients versus controls. The frequency of A*11, A*23, and DRB1*09 alleles was higher, while the frequency of C*12 was lower, in hospitalized patients versus healthy controls albeit with uncorrected statistical significance. The identification of specific allele associations may provide useful future markers for disease susceptibility in order to allow successful clinical management of COVID-19 patients.

Abstract Background A subanalysis of a randomized clinical trial indicated sepsis survival benefit from interleukin (IL)-1 blockade in patients with features of the macrophage activation-like syndrome (MALS). This study aimed to investigate the frequency of MALS and to develop a biomarker of diagnosis and prognosis. Methods Patients with infections and systemic inflammatory response syndrome were assigned to one test cohort (n = 3417) and a validation cohort (n = 1704). MALS was diagnosed for patients scoring positive either for the hemophagocytic syndrome score and/or having both hepatobiliary dysfunction and disseminated intravascular coagulation. Logistic regression analysis was used to estimate the predictive value of MALS for 10-day mortality in both cohorts. Ferritin, sCD163, IL-6, IL-10, IL-18, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) were measured in the blood the first 24 h; ferritin measurements were repeated in 747 patients on day 3. Results The frequency of MALS was 3.7% and 4.3% in the test and the validation cohort, respectively. In both cohorts, MALS was an independent risk factor for 10-day mortality. A ferritin level above 4420 ng/ml was accompanied by 66.7% and 66% mortality after 28 days, respectively. Ferritin levels above 4420 ng/ml were associated with an increase of IL-6, IL-18, INF-γ, and sCD163 and a decreased IL-10/TNF-α ratio, indicating predominance of pro-inflammatory phenomena. Any less than 15% decrease of ferritin on day 3 was associated with more than 90% sensitivity for unfavorable outcome after 10 days. This high mortality risk was also validated in an independent Swedish cohort (n = 109). Conclusions MALS is an independent life-threatening entity in sepsis. Ferritin measurements can provide early diagnosis of MALS and may allow for specific treatment.

Pulmonary fibrosis is a progressive disease characterized by disruption of lung architecture and deregulation of the pulmonary function. Prostacyclin, a metabolite of arachidonic acid, is a potential disease mediator since it exerts anti-inflammatory and anti-fibrotic actions. We investigated the effect of treprostinil, a prostacyclin analogue, in bleomycin-induced experimental pulmonary fibrosis. Bleomycin sulfate or saline was administrated intratracheally to mice ( n = 9–10/group) at day 0. Orotracheal aspiration of treprostinil or vehicle was administered daily and started 24 h prior to bleomycin challenge. Evaluation of lung pathology was performed in tissue samples and bronchoalveolar lavage fluid collected 7, 14 and 21 days after bleomycin exposure. Lung injury was achieved due to bleomycin exposure at all time points as indicated by impaired lung mechanics, pathologic lung architecture (from day 14), and cellular and protein accumulation in the alveolar space accompanied by a minor decrease in lung tissue VE-cadherin at day 14. Treprostinil preserved lung mechanics, and reduced lung inflammation, fibrosis, and vascular remodeling (day 21); reduced cellularity and protein content of bronchoalveolar lavage fluid were additionally observed with no significant effect on VE-cadherin expression. Bleomycin-induced collagen deposition was attenuated by treprostinil from day 14, while treprostinil involvement in regulating inflammatory processes appears mediated by NF-κB signaling. Overall, prophylactic administration of treprostinil, a stable prostacyclin analogue, maintained lung function, and prevented bleomycin-induced lung injury, and fibrosis, as well as vascular remodeling, a hallmark of pulmonary hypertension. This suggests potential therapeutic efficacy of treprostinil in pulmonary fibrosis and possibly in pulmonary hypertension related to chronic lung diseases.

Pulmonary arterial hypertension (PAH) is a heterogenous clinical entity with poor prognosis, despite recent major pharmacological advances. To increase awareness about the pathophysiology, epidemiology, and management of the disease, large national registries are required. The Hellenic pulmOnary hyPertension rEgistry (HOPE) was launched in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. Baseline epidemiologic, diagnostic, and initial treatment data of consecutive patients with PAH are presented in this article. In total, 231 patients with PAH were enrolled from January 2015 until April 2018. At baseline, about half of patients with PAH were in World Health Organization functional class II. The majority of patients with PAH (56.7%) were at intermediate 1-year mortality risk, while more than one-third were low-risk patients, according to an abbreviated risk stratification score. Half of patients with PAH were on monotherapy, 38.9% received combination therapy, while prostanoids were used only in 12.1% of patients. In conclusion, baseline data of the Greek PAH population share common characteristics, but also have some differences with other registries, the most prominent being a better functional capacity. This may reflect earlier diagnosis of PAH that in conjunction with the increased proportion of patients with atypical PAH could partially explain the preference for monotherapy and the limited use of prostanoids in Greece. Nevertheless, early, advanced specific therapy is strongly recommended.

A damaged endothelium is an underlying condition of the many complications of COVID-19 patients. The increased mortality risk associated with diseases that have underlying endothelial dysfunction, such as acute respiratory distress syndrome (ARDS), suggests that endothelial (e) nitric oxide synthase (NOS)-derived nitric oxide could be an important defense mechanism. Additionally, intravenous recombinant angiotensin converting enzyme 2 (ACE2) was recently reported as an effective therapy in severe COVID-19, by blocking viral entry, and thus reducing lung injury. Very few studies exist on the prognostic value of endothelium-related protective molecules in severe COVID-19 disease. To this end, serum levels of eNOS, inducible (i) NOS, adrenomedullin (ADM), soluble (s) ACE2 levels, and serum (s) ACE activity were measured on hospital admission in 89 COVID-19 patients, hospitalized either in a ward or ICU, of whom 68 had ARDS, while 21 did not. In our cohort, the COVID-19-ARDS patients had considerably lower eNOS levels compared to the COVID-19 non-ARDS patients. On the other hand, sACE2 was significantly higher in the ARDS patients. iNOS, ADM and sACE activity did not differ. Our results might support the notion of two distinct defense mechanisms in COVID-19-derived ARDS; eNOS-derived nitric oxide could be one of them, while the dramatic rise in sACE2 may also represent an endogenous mechanism involved in severe COVID-19 complications, such as ARDS. These results could provide insight to therapeutical applications in COVID-19.

Recently, a lower mean pulmonary arterial pressure (PAP) cutoff of >20 mmHg for pulmonary hypertension (PH) definition has been proposed. We examined whether exercise Doppler echocardiography (EDE) can unmask PA hypertension (PAH) in systemic sclerosis (SSc) patients whose baseline echocardiography for PH is equivocal. We enrolled 49 patients with SSc who underwent treadmill EDE. Tricuspid regurgitation (TR) velocity was recorded immediately after EDE. Inotropic reserve of right ventricle (RV) was assessed by the change (post-prior to exercise) of tissue Doppler imaging-derived peak systolic velocity (S) of tricuspid annulus. Inclusion criteria comprised preserved left and RV function, and baseline TR velocity between 2.7 and 3.2 m/s. All patients had right-heart catheterization (RHC) within 48 h after EDE. From 46 patients with good quality of post-exercise TR velocity, RHC confirmed PAH in 21 (45.6%). Post-exercise TR velocity >3.4 m/s had a sensitivity of 90.5%, a specificity of 80% and an accuracy of 84.8% in detecting PAH. Inotropic reserve of RV was positively correlated with maximum achieved workload in METs (r = 0.571, p < 0.001). EDE has a good diagnostic accuracy for the identification of PAH in selected SSc patients whose baseline echocardiographic measurements for PH lie in the gray zone, and it is also potentially useful in assessing RV contractile reserve.

Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

Idiopathic pulmonary arterial hypertension (IPAH) initial evaluation and follow-up, a rare and incurable disease if left untreated, is based on a multiparametric approach (functional status of the patient, biomarkers, hemodynamic parameters and imaging evaluation of right heart impairment). Arterial stiffness (AS) and endothelial glycocalyx are indices of systemic circulation. We present the 3-years follow-up of a female IPAH patient. We propose aortic stiffness and endothelial glycocalyx indices as non-invasive markers of either improvement or deterioration of IPAH disease.

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan–Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan–Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.

Standard echocardiography is important for pulmonary arterial hypertension (PAH) screening in patients with connective tissue disease (CTD), but PAH diagnosis and monitoring require cardiac catheterization. Herein, using cardiac catheterization as reference, we tested the hypothesis that follow-up echocardiography is adequate for clinical decision-making in these patients. We prospectively studied 69 consecutive patients with CTD-associated PAH. Invasive baseline pulmonary artery systolic pressure (PASP) was 60.19 ± 16.33 mmHg (mean ± SD) and pulmonary vascular resistance (PVR) was 6.44 ± 2.95WU. All patients underwent hemodynamic and echocardiographic follow-up after 9.47 ± 7.29 months; 27 patients had a third follow-up after 17.2 ± 7.4 months from baseline. We examined whether clinically meaningful hemodynamic deterioration of follow-up catheterization-derived PASP (i.e., > 10% increase) could be predicted by simultaneous echocardiography. Echocardiography predicted hemodynamic PASP deterioration with 59% sensitivity, 85% specificity, and 63/83% positive/negative predictive value, respectively. In multivariate analysis, successful echocardiographic prediction correlated only with higher PVR in previous catheterization (p = 0.05, OR = 1.235). Notably, in patients having baseline PVR > 5.45 WU, echocardiography had both sensitivity and positive predictive values of 73%, and both specificity and negative predictive value of 91% for detecting hemodynamic PASP deterioration. In selected patients with CTD-PAH echocardiography can predict PASP deterioration with high specificity and negative predictive value. Additional prospective studies are needed to confirm that better patient selection can increase the ability of standard echocardiography to replace repeat catheterization.

Idiopathic pulmonary arterial hypertension (IPAH) has been extensively investigated, although it represents a less common form of the pulmonary hypertension (PH) family, as shown by international registries. Interestingly, in types of PH that are encountered in parenchymal lung diseases such as interstitial lung diseases (ILDs), chronic obstructive pulmonary disease (COPD), and many other diffuse parenchymal lung diseases, some of which are very common, the available data is limited. In this paper, we try to browse in the latest available data regarding the occurrence, pathogenesis, and treatment of PH in chronic parenchymal lung diseases.