Feline infectious peritonitis (FIP), once considered fatal disease with a mortality rate approaching 100%, has experienced a new therapeutic breakthrough in recent years. The aim of our study was to evaluate selected clinicopathological parameters before and after GS- 445124-based treatment of FIP in cats, which could serve as potential candidates for predicting treatment success and monitoring treatment progress.

Pre-treatment haematological parameters in 32 treated cats showed moderate leukocytosis, neutrophilia, lymphopenia and anaemia, which normalised post-treatment. Pre-treatment values of haemogram-derived inflammatory markers (ratio of neutrophils to lymphocytes, platelets to lymphocytes, lymphocytes to monocytes and the systemic immune-inflammatory index) differed significantly from those in the healthy cats and between patients with effusive and non-effusive disease (p < 0.05). Post-treatment, only the ratio of lymphocytes to monocytes remained higher; the other three markers were comparable to the control group. The biochemical results showed characteristic abnormalities (e.g. hyperproteinaemia, hypoalbuminemia, hypergammaglobulinemia, hyperbilirubinemia), which normalised with treatment. Lactate dehydrogenase activities did not differ significantly before and after treatment, except in cats with a relapse and one non-responder, which had markedly elevated values at the time of diagnosis. Analysis of archived blood samples using ELISA revealed significant differences in concentration of acute-phase protein haptoglobin (p = 0.004) and pro-inflammatory cytokine tumour necrosis factor-α (p = 0.028) before and after therapy. Therapy didn't elicit any statistically significant changes in concentrations of ferritin, interleukin- 1β and interleukin- 6.

Our findings demonstrate that successful treatment of FIP leads to highly significant changes in most clinicopathological parameters, including haemogram-derived inflammatory markers. The latter could offer a simple, inexpensive and readily available alternative to the more commonly used acute phase proteins for monitoring FIP treatment. Successful therapy leads to a significant decrease in haptoglobin and an increase in tumour necrosis factor-α. In our study, cats with an unfavourable outcome showed a marked increase in lactate dehydrogenase activity before therapy, suggesting that this parameter could be a promising prognostic factor in larger studies.

Mortality rates among critically ill pediatric patients remain a persistent challenge. It is imperative to identify patients at higher risk to effectively allocate appropriate resources. Our study aimed to develop a prediction score based on clinical parameters and hemogram to predict pediatric intensive care unit (PICU) mortality.

We conducted a retrospective study to develop a clinical prediction score using data from children aged 1 month to 18 years admitted for at least 24 hours to the PICU at Chiang Mai University between January 2018 and December 2022. PICU mortality was defined as death within 28 days of admission. The score was developed using multivariable logistic regression and assessed for calibration and discrimination.

There were 29 deaths in 330 children (8.8%). Our model for predicting 28-day ICU mortality uses four key predictors: male gender, use of vasoactive drugs, red blood cell distribution width (RDW) ≥15.9%, and platelet distribution width (PDW), categorized as follows: <10% (0 points), 10-14.9% (2 points), and ≥15% (4 points). Scores range from 0 to 8, with a cutoff value of 5 to differentiate low-risk (<5) from high-risk (≥5) groups. The tool demonstrates excellent performance with an AuROC curve of 0.86 (95% CI: 0.80-0.91, p<0.001) showing excellent discrimination and calibration, 82.8% sensitivity, and 73.1% specificity, respectively.

The score, developed from clinical data and hemogram, demonstrated potential in predicting ICU mortality among critically ill children. However, further studies are necessary to externally validate the score before it can be confidentially implemented in clinical practices.

Background: Inflammation has been linked to an increased risk of depression, but there is limited and conflicting research on the role of inflammatory markers in adolescent depression. The purpose of this study was to examine associations between cytokines TNF-α, IL-1β, IL-6, and IL-8 and depression among a community-based sample of adolescents (13-19 years of age). Methods: Salivary samples were self-collected by adolescents for assay of cytokines. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms and clinical depression, where a score ≥11 indicated the threshold for experiencing clinical depression. Multiple linear and logistic regression models were used to examine the relationships between cytokines and depression, adjusting for age, sex, ethnicity, income, and body mass index. Results: The mean age of the 83 participants was 15.86 years. Eight participants screened positive for depression; the mean depressive symptom score was 5.11. Higher levels of IL-6 (Coef = 1.33, p < .001) and IL-8 (Coef = 0.69, p = .025) were associated with more frequent depressive symptoms while higher levels of TNF-α (OR = 2.50, p = .002), IL-1β (OR = 1.98, p = .001), and IL-8 (OR = 2.44, p = .008) were associated with greater odds of meeting criteria for clinical depression. Conclusions: Future research should focus on factors that induce higher cytokine levels and the mechanisms underlying their effects on depression. Cytokines assessed in this study may ultimately have implications as methods for depression screening or targets for biologic interventions to prevent and treat adolescent depression.

Thrombotic microangiopathy (TMA) represents a diverse group of conditions characterized by the presence of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and ischemic end-organ injury. Thrombotic thrombocytopenic purpura (TTP) is an important cause of TMA requiring urgent identification and therapeutic plasma exchange (TPE). Cancer-related TMA is commonly misdiagnosed as TTP. In contrast to TTP, there is no clear evidence supporting the routine use of TPE in TMA associated with cancers. However, there are some case reports showing that TPE may also be useful in TMA not associated with TTP, such as cancer-related TMA. In fact, there are different postulated pathophysiology leading to this disease entity. Here, we present a rare case of TMA and acute kidney injury (AKI) secondary to metastatic pancreatic carcinoma who had a resolution of bleeding symptoms with complete hematological and renal recovery after four sessions of daily TPE. The patient finally died of cancer six months later. Our case shows that TPE could be valuable in cancer-related TMA in particular patients, especially those with clinical bleeding and thrombosis. The ability of TPE to remove abnormal components in the complement pathway and potential endothelial-damaging agents or autoantibodies and replace them with normal ones may explain its usefulness in some patients with cancer-related TMA.

The COVID-19 pandemic has raised significant concerns regarding its potential impact on maternal and neonatal health. This study aimed to investigate the immunologic and hemostatic profiles of neonates exposed to SARS-CoV-2 during the peripartum period (0-14 days prior to delivery). This retrospective study included 28 neonates born to COVID-19-positive mothers during the peripartum period and a control group of 54 neonates born to mothers who never tested positive for SARS-CoV-2 during pregnancy. Arterial blood samples were collected from all neonates on the second day of life for the simultaneous assessment of full blood count, C-reactive protein (CRP), serum interleukin-6 (IL-6), and Interferon gamma-induced protein 10 (IP-10) levels, as well as Rotational Thromboelastometry (ROTEM) tests (EXTEM, INTEM, and NATEM). Neonates born to COVID-19-positive mothers and those born to COVID-19-negative mothers exhibited similar coagulation profiles based on ROTEM analysis. Multiple linear regression analysis revealed that peripartum COVID-19 infection was associated with higher IP-10 levels in neonates (coefficient: +16.8, 95% CI: +9.0 to +24.6, p < 0.0001). Our study findings suggest that the presence of immunologic disturbance in neonates is related to recent peripartum exposure to maternal SARS-CoV-2 infection, as evidenced by increased IP-10 levels in blood samples obtained from neonates born to SARS-CoV-2-positive mothers. However, peripartum exposure to maternal SARS-CoV-2 did not appear to disrupt the hemostatic profile of the exposed newborns based on ROTEM test results.

Tuberculosis (TB) induces a hypercoagulable state characterized by systemic inflammation, endothelial dysfunction, and alterations in the coagulation and fibrinolytic pathways. This review explores the pathophysiological mechanisms underlying hypercoagulability in TB, including increased pro-inflammatory cytokine release, endothelial damage, platelet activation, and reduced anticoagulant and fibrinolytic activity. These factors contribute to an elevated risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), which complicate TB prognosis and treatment. The potential role of adjunctive anti-inflammatory therapies, such as vitamin D, NSAIDs, corticosteroids, and anti-platelet agents, is highlighted as a strategy to mitigate systemic inflammation and reduce thrombotic risks in patients with TB. The challenges of anticoagulation therapy, particularly in managing the interactions between anti-TB medications and traditional anticoagulants, are discussed, along with the potential of novel oral anticoagulants (NOAs) as alternatives. We also address therapy of hypercoagulability in TB within resource-limited settings which requires low-cost diagnostics, accessible anticoagulation options, adjunctive therapies, and preventive strategies integrated into existing healthcare systems. Effective risk stratification and individualized management strategies are vital for reducing the morbidity and mortality associated with thrombotic complications in TB.

Cardiovascular complications claim the lives of up to 70% of patients with diabetes mellitus (DM). The mechanisms increasing cardiovascular risk in DM remain to be fully understood and successfully addressed. Nonetheless, there is increasing evidence in the scientific literature of the participation of platelets in the cardiovascular complications of DM. Multiple reports describe the hyperactivity of platelets in DM and their participation in inflammatory responses. The understanding of the mechanisms underlying the contribution of platelets to cardiovascular pathologies in DM will help the development of targeted therapeutic strategies able to reduce cardiovascular risk in these patients. In this literature review, we summarise our current understanding of the molecular mechanisms leading to the contribution of platelets to cardiovascular risk in DM. Both platelet haemostatic activity leading to thrombus formation and their participation to inflammatory processes are stimulated by the biochemical conditions associated with DM. We also present evidence on how DM affect the efficacy of existing therapeutic treatments for thrombosis and, by converse, how antidiabetic drugs may affect platelet function and the haemostasis/thrombosis balance. Taken together, the growing evidence of the different and unexpected roles of platelets in the progression of DM provides a strong rationale for the design of cardiovascular drugs targeting specifically platelets, their pro-inflammatory activity and their activation mechanisms in this disease. Overall, this article provides an important up-to-date overview of the pathophysiological alterations of platelets in DM, which need to be taken into account for the effective management of cardiovascular health in this disease.

Hypercoagulability has been shown to act as an important component of ulcerative colitis (UC) pathogenesis and disease activity, and is strongly correlated with the occurrence of venous thromboembolism (VTE). This study aimed at providing novel therapeutic clues for hypercoagulable active UC.

The coagulation score model was developed using VTE cohorts, and the predictive performance of this model was evaluated by coagulation subtypes of UC patients, which were clustered by the unsupervised method. Subsequently, the response of UC of distinct coagulation types, as identified by the coagulation scoring model, to different biological agents was evaluated. Immunoinflammatory cells and molecules that were associated with hypercoagulable active UC were explored by employing gene set variation analysis, single-sample gene set enrichment analysis, univariate logistic regression analysis, and immunohistochemistry.

A coagulation scoring model was established, which includes five key coagulation factors (ARHGAP35, CD46, BTK, C1QB, and F2R), and accurately distinguished the coagulation subtypes of UC. When comparing anti-TNF-α agents with other biological agents after determining the model, especially golimumab, it showed more effective treatment for hypercoagulable active UC. CXCL8 has been identified as playing an important role in the tightly interconnected network between the immune-inflammatory system and coagulation system in UC. Immunohistochemical analysis showed that the expression of CXCL8, BTK, C1QB, and F2R was upregulated in active UC.

Anti-TNF-α agents have significant therapeutic effects on hypercoagulable active UC, and the strong association between CXCL8, hypercoagulation, and disease activity provides a novel therapeutic insight into hypercoagulable active UC.

This review discusses sources of reactive oxygen species, enzymatic antioxidant systems, and low molecular weight antioxidants. We present the pathology of varicose veins (VVs), including factors such as hypoxia, inflammation, dysfunctional endothelial cells, risk factors in varicose veins, the role of RBCs in venous thrombus formation, the influence of reactive oxygen species (ROS) and RBCs on VV pathology, and the role of hemoglobin in the damage of particles and macromolecules in VVs. This review discusses the production of ROS, enzymatic and nonenzymatic antioxidants, the pathogenesis of varicose veins as a pathology based on hypoxia, inflammation, and oxidative stress, as well as the participation of red blood cells in the pathology of varicose veins.

SUMMARYSARS-CoV-2 can not only cause respiratory symptoms but also lead to neurological complications. Research has shown that more than 30% of SARS-CoV-2 patients present neurologic symptoms during COVID-19 (A. Pezzini and A. Padovani, Nat Rev Neurol 16:636-644, 2020, https://doi.org/10.1038/s41582-020-0398-3). Increasing evidence suggests that SARS-CoV-2 can invade both the central nervous system (CNS) (M.S. Xydakis, M.W. Albers, E.H. Holbrook, et al. Lancet Neurol 20: 753-761, 2021 https://doi.org/10.1016/S1474-4422(21)00182-4 ) and the peripheral nervous system (PNS) (M.N. Soares, M. Eggelbusch, E. Naddaf, et al. J Cachexia Sarcopenia Muscle 13:11-22, 2022, https://doi.org/10.1002/jcsm.12896), resulting in a variety of neurological disorders. This review summarized the CNS complications caused by SARS-CoV-2 infection, including encephalopathy, neurodegenerative diseases, and delirium. Additionally, some PNS disorders such as skeletal muscle damage and inflammation, anosmia, smell or taste impairment, myasthenia gravis, Guillain-Barré syndrome, ICU-acquired weakness, and post-acute sequelae of COVID-19 were described. Furthermore, the mechanisms underlying SARS-CoV-2-induced neurological disorders were also discussed, including entering the brain through retrograde neuronal or hematogenous routes, disrupting the normal function of the CNS through cytokine storms, inducing cerebral ischemia or hypoxia, thus leading to neurological complications. Moreover, an overview of long-COVID-19 symptoms is provided, along with some recommendations for care and therapeutic approaches of COVID-19 patients experiencing neurological complications.

Platelet concentrates (PCs) intended for transfusion contain bioactive molecules that can be considered Biological Response Modifiers (BRMs), mainly originating from plasma regardless of the preparation process. During storage, NGAL and GDF-15 levels increase in single donor apheresis platelet concentrates (SDA-PC), whereas in buffy coat platelet concentrates (BC-PC), the levels of MIP1α, MCP-3, and HSAA increase, and GDF-15 levels decrease. These molecules, primarily released by leukocytes, may contribute to adverse reactions (ARs) following a PC transfusion. Notably, in SDA-PC or BC-PC transfusions that result in ARs, the levels of NGAL, HSAA, and GDF-15 are significantly elevated, while the levels of MDC and CX3CL1 are significantly reduced compared to transfusions without ARs. These biomarkers could potentially serve as predictors for PCs-induced ARs.

Osteoporosis (OP) is a disease characterized by decreased bone mass, deteriorated microstructure, and increased fragility and fracture risk. The diagnosis and prevention of OP and its complications have become major public health challenges. Therefore, exploring the complex ecological connections between the immune and skeletal systems may provide new insights for clinical prevention and treatment strategies.

First, we performed single-cell RNA sequencing on human lumbar lamina tissue and conducted clustering and subgroup analysis of quality-controlled single-cell transcriptome data to identify target subgroups. Subsequently, enrichment analysis and pseudotime analysis were performed. In addition, we conducted in-depth studies on the gene regulatory network between different cell subgroups and the communication between bone immune cells.

In this study, we identified several cell subgroups that may be involved in the progression of OP. For example, the CCL4+ NKT and CXCL8+ neutrophils subgroups promote OP progression by mediating an inflammatory environment that disrupts bone homeostasis, and the MNDA+ Mac subgroup promotes osteoclast differentiation to promote OP. Moreover, the TNFAIP6+ Obl, NR4A2+ B and HMGN2+ erythrocyte subgroups promoted the balance of bone metabolism and suppressed OP. In the cell communication network, Obl closely interacts with immune cell subgroups through the CXCR4-CXCL12, CTGF-ITGB2, and TNFSF14-TNFRSF14 axes.

Our research revealed specific subgroups and intercellular interactions that play crucial roles in the pathogenesis of OP, providing potential new insights for more precise therapeutic interventions for OP.

Increased hemoglobin concentrations may increase the risk of varicose veins. However, the underlying relationship between them was not yet understood.

Mendelian randomization (MR) analysis was performed to investigate causal effect between mean corpuscular hemoglobin concentration (MCHC, exposure factor) and varicose veins (outcome). Afterward, sensitivity analysis was used to ensure the reliability of MR analysis results. Then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of SNPs were performed. A search tool for recurring instances of neighbouring genes (STRING) database was used to construct a protein-protein interaction (PPI) network.

Therefore, the inverse-variance weighted (IVW) results showed there existed a causal relationship between MCHC and varicose veins (p = 0.0026), with MCHC serving as a significant risk factor. (odd ratio [OR] = 1.2321). In addition, the validity of the results of the forward MR analysis was verified by sensitivity analysis. Further, a PPI network of 92 single-nucleotide polymorphisms (SNPs) which used for forward MR analysis related genes was constructed. And they were found to be closely associated with the peroxisome proliferator-activated receptor (PPAR) signalling pathway and cellular response to external stimulus by enrichment analysis. In addition, we clarified that the effect of varicose veins on MCHC was minimal by reverse MR analysis, suggesting that the results of forward MR analysis were not disturbed by reverse results.

This study found a causal relationship between varicose veins and MCHC, which provided strong evidence for the effect of hemoglobin on varicose veins, and a new thought for the diagnosis and prevention of varicose veins in the future.

Generalized epileptic seizures are usually followed by a postictal phase that is often characterized by drowsiness, lethargy, weakness, and confusion. In rare cases, it can present with cutaneous manifestations. Here, we present the case of a 45-year-old male who experienced a seizure and subsequently developed a pinpoint rash with non-blanchable petechiae on various parts of his body. The rash appeared during transport to the emergency department and was resolved after seven days once the seizures were controlled. Initial imaging and basic labs were unremarkable other than a slight increase in postictal markers. No other cause behind this new rash was identified. Our case emphasizes the importance of postictal skin manifestations to aid in diagnosing seizures and avoid unnecessary investigations. The possible pathophysiology behind these generalized non-blanchable petechiae has been attributed to hemodynamic changes and neurogenic inflammation triggered in response to the seizures. Further research into the underlying mechanism and prompt recognition of these symptoms can improve the management of epilepsy care.

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted.

To examine the level of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in the pediatric patient group with keratoconus.

Patients aged 5-18 years with a diagnosis of keratoconus followed by the corneal department and children in the similar age group who were determined as controls were included in the study. Their topographies were evaluated. In both groups, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and mean platelet volume (MPV) were measured.

The study group consisted of children aged 15 ± 1.4 years and the control group 13 ± 1.3 years of age. The mean central corneal thickness of the patients in the patient group was 445.64 μm, and in the control group was 532.25 μm. The NLR was 3.37 ± 1.04 in the patient group and 2.31 ± 0.82 in the control group. The PLR was significantly increased in the KC group (147.54 ± 41.36) than in the control group (118.71 ± 27.11) (P = 0.042). MPV in the patient group was 12.18 ± 2.76 and 7.00 ± 1.37 in the control group. This value was found to be statistically significant (P = 0.047) when the control group and the patient group were compared.

Platelet/lymphocyte ratio and mean platelet volume, which are thought to be new markers of systemic inflammation, may be new indices in keratoconus in pediatric patients.

Thrombosis, a coagulation disorder, occurs due to altered levels of coagulation, fibrinolytic and immune factors, which are otherwise known to maintain hemostasis in normal physiological conditions. Here, we review the direct and indirect participation of a multifunctional nuclear enzyme poly (ADP-ribose) polymerase-1 (PARP1) in the expression of key genes and cellular processes involved in thrombotic pathogenesis. PARP1 biological activities range from maintenance of genomic integrity, chromatin remodeling, base excision DNA repair, stress responses to cell death, angiogenesis and cell cycle pathways. However, under homeostatic imbalances, PARP1 activities are linked with the pathogenesis of diseases, including cancer, aging, neurological disorders, and cardiovascular diseases. Disease-associated distressed cells employ a variety of PARP-1 functions such as oxidative damage exacerbations, cellular energetics and apoptosis pathways, regulation of inflammatory mediators, promotion of endothelial dysfunction, and ERK-mediated signaling in pathogenesis. Thrombosis is one such pathogenesis that comprises exacerbation of coagulation cascade due to biochemical alterations in endothelial cells, platelet activation, overexpression of adhesion molecules, cytokines release, and leukocyte adherence. Thus, the activation of endothelial and inflammatory cells in thrombosis implicates a potential role of PARP1 activation in thrombogenesis. This review article explores the direct impact of PARP1 activation in the etiology of thrombosis and discusses PARP1-mediated endothelial dysfunction, inflammation, and epigenetic regulations in the disease manifestation. Understanding PARP1 functions associated with thrombosis may elucidate novel pathogenetic mechanisms and help in better disease management through newer therapeutic interventions targeting PARP1 activity.

Microscopy imaging has enabled us to establish the presence of fibrin(ogen) amyloid (fibrinaloid) microclots in a range of chronic, inflammatory diseases. Microclots may also be induced by a variety of purified substances, often at very low concentrations. These molecules include bacterial inflammagens, serum amyloid A, and the S1 spike protein of severe acute respiratory syndrome coronavirus 2. Here, we explore which of the properties of these microclots might be used to contribute to differential clinical diagnoses and prognoses of the various diseases with which they may be associated. Such properties include distributions in their size and number before and after the addition of exogenous thrombin, their spectral properties, the diameter of the fibers of which they are made, their resistance to proteolysis by various proteases, their cross-seeding ability, and the concentration dependence of their ability to bind small molecules including fluorogenic amyloid stains. Measuring these microclot parameters, together with microscopy imaging itself, along with methodologies like proteomics and imaging flow cytometry, as well as more conventional assays such as those for cytokines, might open up the possibility of a much finer use of these microclot properties in generative methods for a future where personalized medicine will be standard procedures in all clotting pathology disease diagnoses.

Extracts from Selenicereus monacanthus (synonym: Hylocereus polyrhizus) have received attention due to their potent anti-inflammatory, antioxidant, anticancer, and antidiabetic properties. The current study aims to determine the anti-inflammatory and wound-healing potential of defatted S. monacanthus seed extract (DSMSE). Anti-inflammatory properties of DSMSE on LPS-induced inflammation on THP-1 were determined by measuring the levels of interleukins IL-6, IL-8, and IL-10. Wound healing scratch assay was performed using the human fibroblast (Hs27) cell that assesses the cell migration over 24 h exposure to DSMSE. Administration of DSMSE significantly reduced the LPS-stimulated release levels of IL-6 and IL-8 and significantly increased the levels of IL-10. Treatment with DSMSE showed a significant increase in wound closure with 70% of fibroblast migration. Therefore, the current study showed the anti-inflammatory and wound healing properties of DSMSE reducing inflammatory cytokines (IL-6 and IL-8), increasing IL-10 cytokine, and increasing wound closure at 24 h.

Erythrocytes (RBCs) have a highly specialized and organized membrane structure and undergo programmed cell death, known as eryptosis. Our preliminary data show a significant increase in the eryptosis during peritoneal dialysis (PD)-associated peritonitis. The objectives of the present study were assessment of the incrementation of eryptosis in PD patients with peritonitis, evaluation of the relationship between systemic eryptosis in peritonitis and specific peritonitis biomarkers in PD effluent (PDE), and confirmation of the induction of eryptosis by peritonitis in a vitro setting. We enrolled 22 PD patients with peritonitis and 17 healthy subjects (control group, CTR). For the in vivo study, eryptosis was measured in freshly isolated RBCs. For the in vitro study, healthy RBCs were exposed to the plasma of 22 PD patients with peritonitis and the plasma of the CTR group for 2, 4, and 24 h. Eryptosis was evaluated by flow cytometric analyses in vivo and in vitro. PDE samples were collected for biomarkers analysis.The percentage of eryptotic RBCs was significantly higher in PD patients with peritonitis than in CTR (PD patients with peritonitis: 7.7; IQR 4.3-14.2, versus CTR: 0.8; IQR 0.7-1.3; p < 0.001). We confirmed these in vivo results by in vitro experiments: healthy RBCs incubated with plasma from PD patients with peritonitis demonstrated a significant increase in eryptosis compared to healthy RBCs exposed to plasma from the control group at all times. Furthermore, significant positive correlations were observed between eryptosis level and all analyzed peritoneal biomarkers of peritonitis. We investigated a potential connection between systemic eryptosis and peritoneal biomarkers of peritonitis. Up-regulation of inflammatory markers could explain the increased rate of systemic eryptosis during PD-related peritonitis.

To evaluate the serum levels of HMGB1, IL1β, and α-klotho in COVID-19 patients with different disease severity, investigate their association with clinicopathological parameters, and to assess HMGB1 rs1045411 polymorphism and its relation with clinical severity.

120 COVID-19 patients (89 critically ill, 15 severe, and 16 moderately severe) along with 80 healthy control were enrolled.The serum levels of HMGB1,IL1β, and α-klotho were determined by ELISA. The HMGB1 rs1045411 polymorphism was detected by RT- PCR.

The serum levels of HMGB1, IL1β, and α-klotho were significantly higher in critically ill COVID-19 patients compared to other groups. The HMGB1rs1045411 polymorphism revealed a significant decrease in the percentage of T/T genotypes in COVID-19 patients compared to controls. The (ROC) analysis showed moderate diagnostic potential for serum HMGB1, IL1β, and α-klotho.

The serum HMGB1, IL1β, and α-klotho may be severity markers and promising therapeutic targets for COVID-19 patients.

Individuals who present to a hospital for treatment of a burn of any magnitude are more frequently hospitalised for ischemic heart disease, even decades after injury. Blood platelets are key mediators of cardiovascular disease. To investigate platelet involvement in post-burn cardiovascular risk, platelet reactivity was assessed in patients at 2- and 6-weeks after non-severe (TBSA < 20%) burn injury, and in a murine model 30 days after 8% TBSA full-thickness burn injury. Platelets were stimulated with canonical agonists and function reported by GPIIb/IIIa PAC1-binding site, CD62P expression, and formation of monocyte-platelet aggregates. In vivo thrombosis in a modified Folts model of vascular injury was assessed. Burn survivors had elevated frequencies of circulating monocyte-platelet aggregates, and platelets were hyperreactive, primarily to collagen stimulation. Burn plasma did not cause hyper-reactivity when incubated with control platelets. Platelets from burn injured mice also demonstrated increased response to collagen peptides but did not show any change in thrombosis following vascular injury. This study demonstrates the persistence of a small but significant platelet hyperreactivity following burn injury. Although our data does not suggest this heightened platelet sensitivity modulates thrombosis following vascular injury, the contribution of sub-clinical platelet hyperreactivity to accelerating atherogenesis merits further investigation.

Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG.

This is a pre-specified sub-study of the "Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation" study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1β, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points.

Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines.

High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography.

Blood flow disorders are often the result of the non-physiological narrowing of blood arteries caused by atherosclerosis and thrombus. The blood then proceeds through rising-peak-decreasing phases as it passes through the narrow area. Although abnormally high shear is known to activate platelets, the shear process that platelets undergo in small arteries is complex. Thus, understanding how each shear phase affects platelet activation can be used to improve antiplatelet therapy and decrease the risk of side effects like bleeding. Blood samples were sheared (68.8 ms,5200 s-1) in vitro by the microfluidic technique, and platelet activation levels (P-selectin and integrin αIIbβ3) and von Willebrand factor (vWF) binding to platelets were analyzed by flow cytometry. Post-stenosis platelet aggregation was dynamically detected using microfluidic technology. We studied TXA2, P2Y12-ADP, and integrin αIIbβ3-fibrinogen receptor pathways by adding antiplatelet drugs, such as acetylsalicylic acid (ASA, an active ingredient of aspirin that inhibits platelet metabolism), ticagrelor (hinders platelet activation), and tirofiban (blocks integrin αIIbβ3 receptor) in vitro, respectively, to determine platelet activation function mediated by transient non-physiological high shear rates. We demonstrated that platelets can be activated under transient pathological high shear rates. The shear rise and fall phases influenced shear-induced platelet activation by regulating the binding of vWF to platelets. The degree of platelet activation and aggregation increased with multiple shear rise and fall phases. ASA did not inhibit shear-mediated platelet activation, but ticagrelor and tirofiban effectively inhibited shear-mediated platelet activation. Our data demonstrated that the shear rise and fall phases play an important role in shear-mediated platelet activation and promote platelet activation and aggregation in a vWF-dependent manner. Blocking integrin αIIbβ3 receptor and hindering P2Y12-ADP were beneficial to reducing shear-mediated platelet activation.

Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown.

We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania.

Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites.

Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10-8) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity.

Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet.

Thrombosis is an important contributor to cerebral aneurysm growth and progression. A number of sophisticated multiscale and multiphase in silico models have been developed with a view towards interventional planning. Many of these models are able to account for clotting outcomes, but do not provide detailed insight into the role of flow during clot development. In this study, we present idealised, two-dimensional in silico cerebral fibrin clot model based on computational fluid dynamics (CFD), biochemical modelling and variable porosity, permeability, and diffusivity. The model captures fibrin clot growth in cerebral aneurysms over a period at least 1000 s in five different geometries. The fibrin clot growth results were compared to an experiment presented in literature. The biochemistry was found to be more sensitive to mesh size compared to the haemodynamics, while larger timesteps overpredicted clot size in pulsatile flow. When variable diffusivity was used, the predicted clot size was 25.4% lesser than that with constant diffusivity. The predicted clot size in pulsatile flow was 14.6% greater than in plug flow. Different vortex modes were observed in plug and pulsatile flow; the latter presented smaller intermediate modes where the main vortex was smaller and less likely to disrupt the growing fibrin clot. Furthermore, smaller vortex modes were seen to support fibrin clot propagation across geometries. The model clearly demonstrates how the growing fibrin clot alters vortical structures within the aneurysm sac and how this changing flow, in turn, shapes the growing fibrin clot.

Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients.

This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC.

The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC.

RDW is associated with sarcopenia risk in early-stage NSCLC.

SARS-CoV-2 mRNA vaccination can entail chronic fatigue/dysautonomia tentatively termed post-acute COVID-19 vaccination syndrome (PACVS). We explored receptor autoantibodies and interleukin-6 (IL-6) as somatic correlates of PACVS. Blood markers determined before and six months after first-time SARS-CoV-2 vaccination of healthy controls (N = 89; 71 females; mean/median age: 39/49 years) were compared with corresponding values of PACVS-affected persons (N = 191; 159 females; mean/median age: 40/39 years) exhibiting chronic fatigue/dysautonomia (≥three symptoms for ≥five months after the last SARS-CoV-2 mRNA vaccination) not due to SARS-CoV-2 infection and/or confounding diseases/medications. Normal vaccination response encompassed decreases in 11 receptor antibodies (by 25-50%, p < 0.0001), increases in two receptor antibodies (by 15-25%, p < 0.0001) and normal IL-6. In PACVS, serological vaccination-response appeared significantly (p < 0.0001) altered, allowing discrimination from normal post-vaccination state (sensitivity = 90%, p < 0.0001) by increased Angiotensin II type 1 receptor antibodies (cut-off ≤ 10.7 U/mL, ROC-AUC = 0.824 ± 0.027), decreased alpha-2B adrenergic receptor antibodies (cut-off ≥ 25.2 U/mL, ROC-AUC = 0.828 ± 0.025) and increased IL-6 (cut-off ≤ 2.3 pg/mL, ROC-AUC = 0.850 ± 0.022). PACVS is thus indicated as a somatic syndrome delineated/detectable by diagnostic blood markers.

Several studies have indicated that COVID-19 can lead to alterations in blood rheology, including an increase in red blood cell aggregation. The precise mechanisms behind this phenomenon are not yet fully comprehended. The latest findings suggest that erythrocyte aggregation significantly influences microcirculation, causes the formation of blood clots in blood vessels, and even damages the endothelial glycocalyx, leading to endothelial dysfunction. The focus of this research lies in investigating the cellular factors influencing these changes in aggregation and discussing potential causes and implications in the context of COVID-19 pathophysiology. For this purpose, the aggregation of erythrocytes in a group of 52 patients with COVID-19 pneumonia was examined in a 70 kDa Dextran solution, which eliminates the influence of plasma factors. Using image analysis, the velocities and sizes of the formed aggregates were investigated, determining their porosity. This study showed that the process of erythrocyte aggregation in COVID-19 patients, independent of plasma factors, leads to the formation of more compact, denser, three-dimensional aggregates. These aggregates may be less likely to disperse under circulatory shear stress, increasing the risk of thrombotic events. This study also suggests that cellular aggregation factors can be responsible for the thrombotic disorders observed long after infection, even when plasma factors have normalized. The results and subsequent broad discussion presented in this study can contribute to a better understanding of the potential complications associated with increased erythrocyte aggregation.

Sepsis is a life-threatening multiple-organ dysfunction induced by infection and is one of the leading causes of mortality and critical illness worldwide. The pathogenesis of sepsis involves the alteration of several biochemical pathways such as immune response, coagulation, dysfunction of endothelium and tissue damage through cellular death and/or apoptosis. Recently, in vitro and in vivo studies reported changes in the morphology and in the shape of human red blood cells (RBCs) causing erythrocyte death (eryptosis) during sepsis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure to phosphatidylserine (PS), which attract macrophages. The aim of this study was to evaluate the in vitro induction of eryptosis on healthy RBCs exposed to septic plasma at different time points. Furthermore, we preliminary investigated the in vivo levels of eryptosis in septic patients and its relationship with Endotoxin Activity Assay (EAA), mortality and other biological markers of inflammation and oxidative stress. We enrolled 16 septic patients and 16 healthy subjects (no systemic inflammation in the last 3 months) as a control group. At diagnosis, we measured Interleukin-6 (IL-6) and Myeloperoxidase (MPO). For in vitro study, healthy RBCs were exposed to the plasma of septic patients and CTR for 15 min, 1, 2, 4 and 24 h. Morphological markers of death and eryptosis were evaluated by flow cytometric analyses. The cytotoxic effect of septic plasma on RBCs was studied in vitro at 15 min, 1, 2, 4 and 24 h. Healthy RBCs incubated with plasma from septic patients went through significant morphological changes and eryptosis compared to those exposed to plasma from the control group at all time points (all, p < 0.001). IL-6 and MPO levels were significantly higher in septic patients than in controls (both, p < 0.001). The percentage of AnnexinV-binding RBCs was significantly higher in septic patients with EAA level ≥0.60 (positive EAA: 32.4%, IQR 27.6-36.2) compared to septic patients with EAA level <0.60 (negative EAA: 14.7%, IQR 5.7-30.7) (p = 0.04). Significant correlations were observed between eryptosis and EAA levels (Spearman rho2 = 0.50, p < 0.05), IL-6 (Spearman rho2 = 0.61, p < 0.05) and MPO (Spearman rho2 = 0.70, p < 0.05). In conclusion, we observed a quick and great cytotoxic effect of septic plasma on healthy RBCs and a strong correlation with other biomarkers of severity of sepsis. Based on these results, we confirmed the pathological role of eryptosis in sepsis and we hypothesized its use as a biomarker of sepsis, potentially helping physicians to face important treatment decisions.

The SARS-CoV-2 virus, causing the devastating COVID-19 pandemic, has been reported to affect platelets and cause increased thrombotic events, hinting at the possible bidirectional interactions between platelets and the virus. In this review, we discuss the potential mechanisms underlying the increased thrombotic events as well as altered platelet count and activity in COVID-19. Inspired by existing knowledge on platelet-pathogen interactions, we propose several potential antiviral strategies that platelets might undertake to combat SARS-CoV-2, including their abilities to internalize the virus, release bioactive molecules to interfere with viral infection, and modulate the functions of immune cells. Moreover, we discuss current and potential platelet-targeted therapeutic strategies in controlling COVID-19, including antiplatelet drugs, anticoagulants, and inflammation-targeting treatments. These strategies have shown promise in clinical settings to alleviate the severity of thrombo-inflammatory complications and reduce the mortality rate among COVID-19 patients. In conclusion, an in-depth understanding of platelet-SARS-CoV-2 interactions may uncover novel mechanisms underlying severe COVID-19 complications and could provide new therapeutic avenues for managing this disease.

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest itself in several ways, including coagulopathy and thrombosis. These complications can be the first and sometimes only manifestations of SARS-CoV-2 infection and can occur early or late in the course of the disease. However, these symptoms are more prevalent in hospitalized patients with venous thromboembolism, particularly those admitted to intensive care units. Moreover, various forms of arterial and venous thrombosis, or micro- or macro-vasculature embolisms, have been reported during the current pandemic. They have led to harmful consequences, such as neurological and cardiac events, nearly all resulting from the hypercoagulable state caused by this viral infection. The severe hypercoagulability observed in patients with COVID-19 accounts for most cases of the disease that become critical. Therefore, anticoagulants seem to be one of the most vital therapeutics for treating this potentially life-threatening condition. In the current paper, we present a thorough review of the pathophysiology of COVID-19-induced hypercoagulable state and the use of anticoagulants to treat SARS-CoV-2 infections in different patient groups, as well as their pros and cons.

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening, rare acute thrombotic microangiopathy (TMA), caused by a severe ADAMTS13 deficiency. As the COVID-19 pandemic rapidly spread around the globe, much data about the pathogenicity of this virus were published. Soon after the detection of the first cases of COVID-19, it was clear that there was a wide range of COVID coagulopathy manifestations, such as deep venous thrombosis, pulmonary thromboembolism, and thrombotic microangiopathies. In the literature, little data have been reported about the association between TTP and COVID-19, and the treatment of COVID-19-associated TTP is still under debate. Here we present the case of a 46-year-old woman who developed a COVID-associated TTP, successfully treated with plasma exchange (PEX), steroids, and caplacizumab.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major challenge to be faced in recent years. While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019, children were thought to be exclusively asymptomatic or to present with mild conditions. However, around April 2020, there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children - multisystemic inflammatory syndrome in children (MIS-C) - which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement. The Centers for Disease Control and Prevention considers a suspected case of MIS-C an individual aged < 21 years presenting with fever, high inflammatory markers levels, and evidence of clinically severe illness, with multisystem (> 2) organ involvement, no alternative plausible diagnoses, and positive for recent SARS-CoV-2 infection. Despite its severity, there are no definitive disease management guidelines for this condition. Conversely, the complex pathogenesis of MIS-C is still not completely understood, although it seems to rely upon immune dysregulation. Hence, in this study, we aim to bring together current evidence regarding the pathogenic mechanisms of MIS-C, clinical picture and management, in order to provide insights for clinical practice and implications for future research directions.

COVID-19 is characterized by dysregulated thrombosis and coagulation that can increase mortality in patients. Platelets are fast responders to pathogen presence, alerting the surrounding immune cells and contributing to thrombosis and intravascular coagulation. The SARS-CoV-2 genome has been found in platelets from patients with COVID-19, and its coverage varies according to the method of detection, suggesting direct interaction of the virus with these cells. Antibodies against Spike and Nucleocapsid have confirmed this platelet-viral interaction. This review discusses the immune, prothrombotic, and procoagulant characteristics of platelets observed in patients with COVID-19. We outline the direct and indirect interaction of platelets with SARS-CoV-2, the contribution of the virus to programmed cell death pathway activation in platelets and the consequent extracellular vesicle release. We discuss platelet activation and immunothrombosis in patients with COVID-19, the effect of Spike on platelets, and possible activation of platelets by classical platelet activation triggers as well as contribution of platelets to complement activation. As COVID-19-mediated thrombosis and coagulation are still not well understood in vivo, we discuss available murine models and mouse adaptable strains.

Okadaic acid (OA), a lipophilic phycotoxin distributed worldwide, causes diarrheic shellfish poisoning and even leads to tumor formation. Currently, the consumption of contaminated seafood is the most likely cause of chronic OA exposure, but there is a serious lack of relevant data. Here, the Sprague-Dawley rats were exposure to OA by oral administration at 100 µg/kg body weight, and the tissues were collected and analyzed to assess the effect of subchronic OA exposure. The results showed that subchronic OA administration disturbed colonic mucosal integrity and induced colitis. The colonic tight junction proteins were disrupted and the cell cycle of colonic epithelial cells was accelerated. It is inferred that disruption of the colonic tight junction proteins might be related to the development of chronic diarrhea by affecting water and ion transport. Moreover, the accelerated proliferation of colonic epithelial cells indicated that subchronic OA exposure might promote the restitution process of gut barrier or induce tumor promoter activity in rat colon.

COVID-19 infection and vaccination offer disparate levels of defense against reinfection and breakthrough infection. This study was designed to examine the effects of curcumin supplementation, specifically HydroCurc (CURC), versus placebo (CON) on circulating inflammatory biomarkers in adults who had previously been diagnosed with COVID-19 and subsequently received a primary series of monovalent vaccine doses. This study was conducted between June 2021 and May 2022. Participants were randomized to receive CURC (500 mg) or CON capsules twice daily for four weeks. Blood sampling was completed at baseline and week-4 and analyzed for biomarkers. Linear regression was utilized to examine the between-group differences in post-trial inflammatory biomarker levels, adjusting for baseline and covariates including age, sex, race/ethnicity, and interval between COVID-19 diagnosis and trial enrollment. The sample (n = 31) was 71% female (Age 27.6 ± 10.4 y). The CURC group exhibited significantly lower post-trial concentrations of proinflammatory IL-6 (β = -0.52, 95%CI: -1.03, -0.014, p = 0.046) and MCP-1 (β = -0.12, 95%CI: -0.23, -0.015, p = 0.027) compared to CON, adjusting for baseline and covariates. Curcumin intake confers anti-inflammatory activity and may be a promising prophylactic nutraceutical strategy for COVID-19. These results suggest that 4 weeks of curcumin supplementation resulted in significantly lower concentrations of proinflammatory cytokines in adults who recovered from COVID-19 infection and were subsequently vaccinated.

Coronavirus disease 2019 (COVID-19) is a rapidly spreading acute respiratory infection caused by SARS-CoV-2. The pathogenesis of the disease remains unclear. Recently, several hypotheses have emerged to explain the mechanism of interaction between SARS-CoV-2 and erythrocytes, and its negative effect on the oxygen-transport function that depends on erythrocyte metabolism, which is responsible for hemoglobin-oxygen affinity (Hb-O2 affinity). In clinical settings, the modulators of the Hb-O2 affinity are not currently measured to assess tissue oxygenation, thereby providing inadequate evaluation of erythrocyte dysfunction in the integrated oxygen-transport system. To discover more about hypoxemia/hypoxia in COVID-19 patients, this review highlights the need for further investigation of the relationship between biochemical aberrations in erythrocytes and oxygen-transport efficiency. Furthermore, patients with severe COVID-19 experience symptoms similar to Alzheimer's, suggesting that their brains have been altered in ways that increase the likelihood of Alzheimer's. Mindful of the partly assessed role of structural, metabolic abnormalities that underlie erythrocyte dysfunction in the pathophysiology of Alzheimer's disease (AD), we further summarize the available data showing that COVID-19 neurocognitive impairments most probably share similar patterns with known mechanisms of brain dysfunctions in AD. Identification of parameters responsible for erythrocyte function that vary under SARS-CoV-2 may contribute to the search for additional components of progressive and irreversible failure in the integrated oxygen-transport system leading to tissue hypoperfusion. This is particularly relevant for the older generation who experience age-related disorders of erythrocyte metabolism and are prone to AD, and provide an opportunity for new personalized therapies to control this deadly infection.

Coronavirus disease 2019 (COVID-19), which is caused by novel coronavirus-2019 (nCoV-2019), is a highly contagious disease with high mortality and morbidity risk. Infected people may suffer from respiratory infections, which may be more progressive in patients with a defective immune system and underlying medical problems. In this regard, the cells involved in the innate immune system, play a decisive role in disease progression and complication development. Pathogen entrapment is the critical role of neutrophil extracellular traps (NETosis). This process involves the widespread release of fibrous structures by the stimulant-activated neutrophils. These fibrous structures are composed of cytosolic proteins and granular contents brought together by a network of released chromatins. This network can inhibit the spread of pathogens by their entrapment. Moreover, NETosis damage the host by producing toxic agents and triggering thrombosis. Therefore, this phenomenon may act as a double-edged sword. Regarding the rapid expansion of COVID-19, it is crucial to examine the involvement of NETosis in infected patients. This study aims to discuss NETosis participation to show its probable association with increased risk of thrombogenicity and help develop new therapeutic approaches in the battle against this viral disease.

SARS-CoV-2 infection causes a considerable inflammatory response coupled with impaired platelet reactivity, which can lead to platelet disorders recognized as negative prognostic factors in COVID-19 patients. The virus may cause thrombocytopenia or thrombocytosis during the different disease stages by destroying or activating platelets and influencing platelet production. While it is known that several viruses can impair megakaryopoiesis by generating an improper production and activation of platelets, the potential involvement of SARS-CoV-2 in affecting megakaryopoiesis is poorly understood. To this purpose, we explored, in vitro, the impact of SARS-CoV-2 stimulation in the MEG-01 cell line, a human megakaryoblastic leukemia cell line, considering its spontaneous capacity of releasing platelet-like particles (PLPs). We interrogated the effect of heat-inactivated SARS-CoV-2 lysate in the release of PLPs and activation from MEG-01, the signaling pathway influenced by SARS-CoV-2, and the functional effect on macrophagic skewing. The results highlight the potential influence of SARS-CoV-2 in the early stages of megakaryopoiesis by enhancing the production and activation of platelets, very likely due to the impairment of STATs signaling and AMPK activity. Overall, these findings provide new insight into the role of SARS-CoV-2 in affecting megakaryocyte-platelet compartment, possibly unlocking another avenue by which SARS-CoV-2 moves.

Primary blast lung injury (PBLI), caused by exposure to high-intensity pressure waves from explosions in war, terrorist attacks, industrial production, and life explosions, is associated with pulmonary parenchymal tissue injury and severe ventilation insufficiency. PBLI patients, characterized by diffused intra-alveolar destruction, including hemorrhage and inflammation, might deteriorate into acute respiratory distress syndrome (ARDS) with high mortality. However, due to the absence of guidelines about PBLI, emergency doctors and rescue teams treating PBLI patients rely on experience. The goal of this review is to summarize the mechanisms of PBLI and their cross-linkages, exploring potential diagnostic and therapeutic targets of PBLI. We summarize the pathophysiological performance and pharmacotherapy principles of PBLI. In particular, we emphasize the crosstalk between hemorrhage and inflammation, as well as coagulation, and we propose early control of hemorrhage as the main treatment of PBLI. We also summarize several available therapy methods, including some novel internal hemostatic nanoparticles to prevent the vicious circle of inflammation and coagulation disorders. We hope that this review can provide information about the mechanisms, diagnosis, and treatment of PBLI for all interested investigators.