COVID-19 infection-related coagulopathy and viscoelastic methods: A paradigm for their clinical utility in critical illness

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Association of malnutrition with periprosthetic joint and surgical site infections after total joint arthroplasty: a systematic review and meta-analysis

Background: A growing body of evidence associates malnutrition with several adverse outcomes. Aim: To investigate the link between malnutrition with surgical site and periprosthetic joint infections (SSIs and PJIs) following total knee and hip arthroplasty (TKA and THA) through a comprehensive meta-analysis of observational studies. Methods: A systematic search was conducted on PubMed and Scopus databases through December 2018, and recent proceedings of major orthopaedic meetings. Data from eligible studies were extracted and synthesized; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Findings: Seven publications were included, reporting eight independent cohort studies with >250,000 subjects. SSIs and PJIs were more likely to develop in malnourished patients (OR: 2.49; 95% CI: 2.13–2.90; and 3.62; 2.33–5.64, respectively). The association of SSI with malnutrition was evident both after TKA (2.42; 1.94–3.02) and after THA (2.66; 1.64–4.30). Similarly, PJI was associated with malnutrition after TKA (2.55; 1.10–5.91) and after THA (3.10; 1.84–5.25). Finally, PJI correlated with malnutrition both after primary arthroplasty (3.58; 1.82–7.03) and revision arthroplasty (3.96; 2.47–6.33). The subgroup analysis by study setting confirmed the relationship between PJI and malnutrition in hospital (6.02; 3.07–11.81) and population-based (2.80; 1.76–4.44) studies. Conclusion: Malnutrition is associated with PJIs and SSIs after total joint arthroplasty. Further high-quality research is warranted to confirm or refute these findings. © 2019 The Healthcare Infection Societ

Redox imbalance, macrocytosis, and RBC homeostasis

The erythrocyte represents a major component of the antioxidant capacity of the blood through the enzymes contained in the cell, the glutathione system, and the low-molecular-weight antioxidants of the erythrocyte membrane. A further major red blood cell contribution is in regenerating consumed redox equivalents via the oxidative pentose phosphate pathway and glutathione reductase. Moreover, its extracellular antioxidant capacity, its mobility, and the existence of reducing equivalents far in excess of its normal requirements make erythrocytes function as an effective oxidative sink in the organism. That is why red blood cell metabolism and homeostasis strongly affect the antioxidant properties of the whole body. Conversely, the relation between macrocytosis and oxidative stress has not been fully delineated. Reviewing the mechanisms involved in red blood cell homeostasis in cases of redox imbalance is crucial in identification of factors that could potentially improve erythrocyte survival and defense against oxidant damage. © Mary Ann Liebert, Inc

Nucleated red blood cells: Could they be indicator markers of illness severity for neonatal intensive care unit patients?

Background: We aimed to assess whether nucleated red blood cells (NRBCs) count could serve as a diagnostic and prognostic biomarker for morbidity and mortality in critically ill neonates. Methods: The association between NRBCs count and neonatal morbidity and mortality was evaluated in an observational cohort of critically ill neonates hospitalized in our neonatal intensive care unit over a period of 69 months. The discriminative ability of NRBCs count as diagnostic and prognostic biomarkers was evaluated by performing the Receiver Operating Characteristics (ROC) curve analysis. Results: Among 467 critically ill neonates included in the study, 45 (9.6%) of them experienced in-hospital mortality. No statistically significant difference was found with regards to NRBCs count between survivors and non-survivors, although the median value for NRBCs was sometimes higher for non-survivors. ROC curve analysis showed that NRBCs is a good discriminator marker for the diagnosis of perinatal hypoxia in neonates with area under the curve (AUC) [AUC 0.710; 95% confidence interval (CI), 0.660–0.759] and predominantly in preterm neonates (AUC 0.921 (95% CI, 0.0849–0.0993)) by using a cut-off value of ≥11.2%, with 80% sensitivity and 88.7% specificity. NRBCs also revealed significant prognostic power for mortality in septic neonates (AUC 0.760 (95% CI, 0.631–0.888)) and especially in preterms with sepsis (AUC 0.816 (95% CI, 0.681–0.951)), with cut-off value ≥ 1%, resulting in 81.6% sensitivity and 78.1% specificity. Conclusion: NRBCs count may be included among the early diagnostic and prognostic markers for sick neonates. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Erratum: Thromboelastometry Variables in Neonates with Perinatal Hypoxia (Seminars in Thrombosis and Hemostasis DOI: 10.1055/s-0040-1709473)

The authors have informed the publisher that the last name for Nicoletta Iacovidou was incorrectly spelled as Lacovidou in the above article published on May 21, 2020 (Doi: 10.1055/s-0040-1709473). The name has now been corrected in the aforementioned article. © 2020 Thieme Medical Publishers, Inc.. All rights reserved

The Non-Activated Thromboelastometry (NATEM) Assay’s Application among Adults and Neonatal/Pediatric Population: A Systematic Review

The non-activated thromboelastometry (NATEM) assay is a point-of-care assay that can provide a comprehensive insight into the actual hemostatic mechanism. However, there are very limited data about its use in clinical practice. The aim of this study was to systematically review the literature for any data regarding the use of NATEM in several clinical settings. A systematic review of PubMed and Scopus databases was conducted through 20 January 2022 for studies evaluating the use of the NATEM assay in different clinical settings. The literature search yielded a total of 47 publications, 30 of which met the eligibility criteria for this review. Evaluation of NATEM’s detecting ability for hemostasis disorders is limited in the literature. The results of the included studies indicate that NATEM seems to be a sensitive method for the detection of hyperfibrinolysis and may have an advantage in the diagnosis of hemostatic disorders. It could be more informative than the other ROTEM assays for detecting changes in coagulation parameters in patients who receive anticoagulants. However, the reported outcomes are highly varying among the included studies. NATEM has a high sensitivity to detect hypo-or hypercoagulability and provides a detailed insight into the whole hemostatic process from clot formation to clot breakdown. It could be a useful technique in variable fields of medicine, not only in adults, but also in pediatric and neonatal populations, to guide different hemostatic treatments and predict coagulation disorders or mortality/morbidity; this issue remains to be further investigated. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

The brain-gut axis: Psychological functioning and inflammatory bowel diseases

The brain-gut axis represents a complex bi-directional system comprising multiple inter-connections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. Depression and anxiety are prevalent among patients with chronic disorders characterized by a strong immune component, such as diabetes mellitus, cancer, multiple sclerosis, rheumatoid arthritis and IBD. Although psychological problems are an important aspect of morbidity and of impaired quality of life in patients with IBD, depression and anxiety continue to be under-diagnosed. There is lack of evidence regarding the exact mechanisms by which depression, anxiety and cognitive dysfunction may occur in these patients, and whether psychological disorders are the result of disease activity or determinants of the IBD occurrence. In this comprehensive re-view, we summarize the role of the brain-gut axis in the psychological functioning of patients with IBD, and discuss current preclinical and clinical data on the topic and therapeutic strategies poten-tially useful for the clinical management of these patients. Personalized pathways of psychological supports are needed to improve the quality of life in patients with IBD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Coagulation profiles of pulmonary arterial hypertension patients, assessed by non-conventional hemostatic tests and markers of platelet activation and endothelial dysfunction

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. © 2020 by the authors

The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk

Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences. © 2007 Elsevier Ltd. All rights reserved