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Inhibition of p38 mitogen-activated protein kinase (MAPKs) is a potential therapeutic approach for the treatment of acute and chronic pulmonary inflammatory conditions. Here, we report the in vitro and in vivo characterization of the anti-inflammatory effects of CHF6297, a novel potent and selective p38α inhibitor designed for inhalation delivery as a dry powder formulation. CHF6297 has been proven to inhibit p38α enzymatic activity with sub-nanomolar potency (IC50 = 0.14 ± 0.06 nM), with >1,000-fold selectivity against p38γ and p38δ. In human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides (LPS), as well as in human bronchial epithelial cells (BEAS2B) stimulated with TNF-α or cigarette smoke extract (CSE), CHF6297 inhibited interleukin (IL)-8 release with low nanomolar potency. CHF6297 administered to rats by using a nose-only inhalation device as a micronized dry powder formulation blended with lactose dose-dependently inhibited the LPS-induced neutrophil influx in the bronchoalveolar lavage fluid (BALF). CHF6297 administered intratracheally to rats dose-dependently counteracted the IL-1β (0.3 mg/kg)-induced neutrophil influx (ED50 = 0.22 mg/kg) and increase in IL-6 levels (ED50 = 0.82 mg/kg) in the BALF. In mice exposed to tobacco smoke (TS), CHF6297, administered intranasally (i.n.) for 4 days at 0.03 or 0.3 mg/kg, dose-dependently inhibited the corticosteroid-resistant TS-induced neutrophil influx in the BALF. In a murine house dust mite (HDM) model of asthma exacerbated by influenza virus A (IAV) (H3N3), CHF6297 (0.1 mg/kg, i.n.) significantly decreased airway neutrophilia compared to vehicle-treated IAV/HDM-challenged mice. When CHF6297, at a dose ineffective per se (0.03 mg/kg), was added to budesonide, it augmented the anti-inflammatory effects of the steroid. Overall, CHF6297 effectively counteracted lung inflammation in experimental models where corticosteroids exhibit limited anti-inflammatory activity, suggesting a potential for the treatment of acute exacerbations associated with chronic obstructive pulmonary disease (COPD) and asthma, acute lung injury (ALI), and viral-induced hyperinflammation. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion With chronic transfusion in sickle cell disease (SCD), equipoise exists regarding whether increasing the post‐procedure hematocrit (Hct) suppresses endogenous erythropoiesis. Reticulocytosis predicts SCD morbidity and mortality, so this study's objective was to clarify the role of the post‐procedure Hct in suppressing reticulocytosis and to identify other potential red cell exchange (RCE) parameters predictive of reticulocytosis.This retrospective analysis of 17 patients who underwent chronic RCE at a single institution between 2014 and 2022 examined both standard red cell exchanges (SRCE) and exchanges preceded by isovolemic hemodilution (IVH‐RCE). Post‐procedure parameters with biologic plausibility to influence the subsequent procedure's absolute reticulocyte count (sPre‐ARC) were examined using regression modeling.Neither post‐hematocrit, nor post‐hemoglobin (Hb), nor ΔHb/day was associated with sPre‐ARC or the change in HbS% per day (ΔHbS%/day). Concurrent Hb was predictive for SRCE but not IVH‐RCE, where ARC trended lower than with SRCE. Male gender and post‐procedure neutrophil and white cell counts were predictors of sPre‐ARC, consistent with their associations with SCD morbidity and mortality. IVH‐RCE had a stronger correlation than standard RCE between pre‐Hct and neutrophil or white cell depletion.Although targeting a post‐procedure Hct maintains a higher subsequent pre‐procedure Hb and a lower sPre‐HbS%, it does not lead to sustained suppression of reticulocytosis as measured by the sPre‐ARC or the ΔHbS%/day. IVH‐RCE or the addition of hydroxyurea could be considered in those patients with high reticulocyte, white blood cell, or neutrophil counts. [ABSTRACT FROM AUTHOR]

Background. Spontaneous bacterial peritonitis (SBP) is a life-threatening infection in patients with portal hypertension (PH) and ascites. Its prevention and treatment are vital to improve the prognosis in decompensated PH. Alterations in gut microbiota, gut permeability, and systemic immune dysfunction are cornerstones in the development of SBP in patients with PH. This contributes to the translocation of bacteria from the intestinal lumen to the mesenteric lymph nodes, and then to the portal and systemic circulation from where the ascitic fluid can be colonized with the subsequent development of peritonitis. The purpose was to monitor the course of the disease and determine the possibility of correcting pathological factors of SBP such as bacterial contamination and volume of ascitic fluid, nature of bacterial contamination, increased intra-abdominal pressure, hypoalbuminemia, and to evaluate the role of antibacterial therapy, paracentesis in the treatment of patients with SBP in decompensated PG. Materials and methods. Examination and treatment of 242 patients with ascites who were admitted for emergency medical care were carried out. Diagnostic paracentesis was performed to examine ascitic fluid, which allowed to detect neutrophilia > 250 cells in 1 mm3 in 194 (80.2 %) patients and indicated the presence of SBP. These patients made up the first group of observation. In the second group, there were 48 (19.8 %) patients with no clinical and laboratory signs of SBP at the time of hospitalization. Methodology of analysis of actual research material: to find a statistical difference between the distribution of nominal data of patients in this study, we used Pearson’s χ2 test. To establish the strength of the relationship between variables, we determined the polychoric correlation coefficient. When a statistically significant difference was detec-ted, a stratification analysis was performed with determination of the 95% confidence interval of the odds ratio (Clopper-Pearson method) and the risk ratio for the development of complications in PH. Results. Empiric antibacterial therapy, which was carried out from the moment of receiving information about SBP and began with the use of broad-spectrum antibiotics, was successful in 41 % of cases that was confirmed by repeated examination of ascitic fluid. In antibiotic resistance, determining the sensitivity of ascitic microflora led to a delay in an effective anti-inflammatory treatment and affected the results. In the first group, 39 (20.1 %) patients died, in the second group, 22 (50 %), total mortality was 25.2 %. Conclusions. Diagnostic paracentesis combined with the assessment of bacterial contamination of ascitic fluid, evaluation of intra-abdominal pressure, state of osmoregulation based on albumin concentration is a safe and informative method of diagnosing the severity of pathological process in patients with complicated PH. Treatment of SBP requires urgent care, both in terms of elimination of the infectious factor, and normalization of the disturbed mechanisms of reabsorption regulation by peritoneal and hepatorenal processes. High mortality in patients with SBP is due to the development of inflammation in the abdominal cavity against the background of progressive hepatorenal insufficiency and the inability to correct decompensated PH.

Heightened unfolded protein responses (UPRs) are associated with the risk for asthma, including severe asthma. Treatment-refractory severe asthma manifests a neutrophilic phenotype with T helper (Th)17 responses. However, how UPRs participate in the deregulation of Th17 cells leading to neutrophilic asthma remains elusive. This study found that the UPR sensor IRE1 is induced in the murine lung with fungal asthma and is highly expressed in Th17 cells relative to naive CD4+ T cells. Cytokine (e.g., IL-23) signals induce the IRE1–XBP1s axis in a JAK2-dependent manner. This noncanonical activation of the IRE1–XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse Th17 cells. Ern1 (encoding IRE1) deficiency decreases the expression of endoplasmic reticulum stress factors and impairs the differentiation and cytokine secretion of Th17 cells. Genetic ablation of Ern1 leads to alleviated Th17 responses and airway neutrophilia in a fungal airway inflammation model. Consistently, IL-23 activates the JAK2–IRE1–XBP1s pathway in vivo and enhances Th17 responses and neutrophilic infiltration into the airway. Taken together, our data indicate that IRE1, noncanonically activated by cytokine signals, promotes neutrophilic airway inflammation through the UPR-mediated secretory function of Th17 cells. The findings provide a novel insight into the fundamental understanding of IRE1 in Th17-biased TH2-low asthma. [ABSTRACT FROM AUTHOR]

Background: Polycythemia Rubra Vera (PRV) is a myeloproliferative neoplasm characterized by uncontrolled red blood cell production. This study aimed to evaluate the applicability of the 2016 WHO diagnostic criteria for PRV in Sulaimaniyah City, Kurdistan Region, Iraq, focusing on the incidence of JAK2 mutations and their association with patient demographics and clinical features. Materials & Methods: A cross-sectional retrospective study was conducted on 100 PRV patients between February 2023 and February 2024 at Hiwa Hematology/Oncology Hospital and Shorsh Teaching Hospital. Patients were selected using a convenience sampling method, which involved including all eligible patients with available JAK2 mutation data and bone marrow examination results during the study period. Blood parameters, bone marrow examination, and JAK2 mutation status were analyzed. Statistical associations between JAK2 mutation status and age, gender, and clinical features (neutrophilia, thrombocytosis, splenomegaly) were assessed. Results: The mean age of the patients was 52.91 ± 16.76 years, with 51% older than 50 years. Males comprised 68% of the cohort. Among the patients, 47% were JAK2 mutation-positive, and 53% were JAK2-negative. JAK2- positive patients were significantly older (mean age 57.51 ±17.84 years) compared to JAK2-negative patients (mean age 48.83 ± 14.73 years; p=0.009). A significant association was found between JAK2 mutation status and gender (p=0.01), with a higher proportion of males among JAK2-negative patients. JAK2-positive patients showed higher incidences of neutrophilia (25.5% vs. 3.8%; p=0.002), thrombocytosis (46.8% vs. 13.2%; p<0.001), and splenomegaly (53.2% vs. 9.4%; p<0.001) compared to JAK2-negative patients. Conclusions: The study revealed that while the 2016 WHO criteria are generally effective for diagnosing PRV, the higher-than-expected proportion of JAK2-negative patients suggests the need for additional diagnostic considerations in this population. The significant associations between JAK2 mutation status and specific clinical features emphasize the heterogeneity of PRV presentations and the potential need for regional adaptations of the WHO criteria. [ABSTRACT FROM AUTHOR]

We previously reported that myeloperoxidase-deficient (MPO-/-) mice develop more severe neutrophil-rich lung inflammation than wild-type mice following intranasal Zymosan administration. Interestingly, we found that these mutant mice with severe lung inflammation also displayed pronounced neutrophilia and anemia, characterized by increased granulopoiesis and decreased erythropoiesis in the bone marrow, compared to wild-type mice. This condition was associated with higher concentrations of granulocyte-colony stimulating factor (G-CSF) in both the lungs and serum, a factor known to enhance granulopoiesis. Neutrophils accumulating in the lungs of MPO-/- mice produced greater amounts of G-CSF than those in wild-type mice, indicating that they are a significant source of G-CSF. In vitro experiments using signal transduction inhibitors and Western blot analysis revealed that MPO-/- neutrophils express higher levels of G-CSF mRNA in response to Zymosan, attributed to the upregulation of the IκB kinase/nuclear factor (NF)-κB pathway and the extracellular-signal-regulated kinase/NF-κB pathway. These findings highlight MPO as a critical regulator of granulopoiesis and erythropoiesis in inflamed tissues.

The identification of patients with poor prognosis and early detection of COVID-19 disease complications are made possible by pathological analyses of routine hematological, coagulation, and biochemical tests. Interpreting analyses needs to be done within the framework of each patient's unique clinical picture. It's also critical to keep an eye on changes at the individual parameter level. From May 20th, 2021, to March 30th, 2024, a comprehensive search of literature was carried out using international databases, such as PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. The research question was formulated using the PICO strategy. The following terms were used: biochemical parameters in COVID-19, hematological parameters in COVID-19, blood coagulation parameters in COVID-19, indicators of inflammation, and indicators of tissue damage in SARS-CoV-2. Routine hematological, coagulation, and biochemical tests are primarily used to monitor the progression of the disease and the effectiveness of treatment rather than being utilized for the established diagnosis of COVID-19 due to their low specificity. Molecular genetics and immunological techniques should be used to determine the COVID-19 disease diagnosis. [ABSTRACT FROM AUTHOR]

Rationale: Acute respiratory distress syndrome (ARDS) has an unacceptably high mortality rate (35%) and is without effective therapy. Orai1 is a Ca2+ channel involved in store-operated Ca2+ entry (SOCE), a process that exquisitely regulates inflammation. Orai1 is considered a druggable target, but no Orai1-specific inhibitors exist to date. Objectives: To evaluate whether ELD607, a first-in-class Orai1 antagonist, can treat ARDS caused by bacterial pneumonia in preclinical models. Methods: ELD607 pharmacology was evaluated in HEK293T cells and freshly isolated immune cells from patients with ARDS. A murine acute lung injury model caused by bacterial pneumonia was then used: mice were infected with Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus, or multidrug-resistant P. aeruginosa and then treated with ELD607 intranasally. Measurements and Main Results: ELD607 specifically inhibited SOCE in HEK293T cells with a half-maximal inhibitory concentration of 9 nM. ELD607 was stable in ARDS airway secretions and inhibited SOCE in ARDS immune cells. In vivo, inhaled ELD607 significantly reduced neutrophilia and improved survival. Surprisingly, Orai1 inhibition by ELD607 caused a significant reduction in lung bacteria, including methicillin-resistant S. aureus. ELD607 worked as an immunomodulator that reduced cytokine levels, reduced neutrophilia, and promoted macrophage-mediated resolution of inflammation and clearance of bacteria. Indeed, when alveolar macrophages were depleted with inhaled clodronate, ELD607 was no longer able to resolve inflammation or clear bacteria. Conclusions: These data indicate that specific Orai1 inhibition by ELD607 may be a novel approach to reduce multiorgan inflammation and treat antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background: The complete blood count (CBC) profile has been found extremely useful in monitoring the growth of SARS-CoV-2 infection; however, predictive CBC parameters that could be used in the management of the disease may vary in different populations. Methods: This study comparatively analyzed the CBC profile of SARS-CoV-2 patients (N = 75; confirmed positive by real-time polymerase chain reaction [PCR]) and healthy individuals (confirmed negative by real-time PCR) from Kashmir (north India). Results: Compared with healthy individuals, most of the CBC parameters (hemoglobin levels [13.43 vs 10.9 g/dL; P = 0.0001], lymphocytes [16.04% vs 30.8%; P = 0.00001], monocytes [5.53% vs 7.53%; P = 0.009], and platelet count [150 vs 186 ×103 µL; P = 0.037]) were significantly low in SARS-CoV-2 infected patients, while neutrophilia was more common in infected patients (76.77% vs 59.26%). Among derived parameters, the neutrophil-to-lymphocyte ratio (NLR; 7.31 vs 2.04; P = 0.001) and derived NLR (d-NLR; 4.43 vs 1.5; P = 0.0002) were significantly high in SARS-CoV-2 patients. Further correlation analysis revealed a significant association of neutrophilia with the severity of the disease in SARS-CoV-2 infected patients. Moreover, receiver operating characteristic (ROC) analysis of derived CBC parameters (NLR, d-NLR, and platelet‐to-lymphocyte ratio [PLR] with disease severity and disease outcome) revealed d-NLR as better predictive marker of disease severity (area under the curve [AUC] = 0.658) and disease outcome (AUC = 0.766) compared to PLR with disease severity (AUC = 0.645) and disease outcome (AUC = 0.693). Conclusion: We therefore conclude, of the CBC parameters neutrophilia as the marker of disease severity and among derived parameters, d-NLR as an early predictive biomarker of both disease severity and poor disease outcome in SARS-CoV-2 patients.

Background: The complete blood count (CBC) profile has been found extremely useful in monitoring the growth of SARS-CoV-2 infection; however, predictive CBC parameters that could be used in the management of the disease may vary in different populations. Methods: This study comparatively analyzed the CBC profile of SARS-CoV-2 patients (N=75; confirmed positive by real-time polymerase chain reaction [PCR]) and healthy individuals (confirmed negative by real-time PCR) from Kashmir (North India). Results: Compared with healthy individuals, most of the CBC parameters (hemoglobin levels [13.43 vs 10.9 g/dL; P = 0.0001], lymphocytes [16.04% vs 30.8%; P = 0.00001], monocytes [5.53% vs 7.53%; P = 0.009], and platelet count [150 vs 186 ×103 µL; P = 0.037]) were significantly low in SARS-CoV-2 infected patients, while neutrophilia was more common in infected patients (76.77% vs 59.26%). Among derived parameters, the neutrophil-to-lymphocyte ratio (NLR; 7.31 vs 2.04; P = 0.001) and derived NLR (d-NLR; 4.43 vs 1.5; P = 0.0002) were significantly high in SARS-CoV-2 patients. Further correlation analysis revealed a significant association of neutrophilia with the severity of the disease in SARS-CoV-2 infected patients. Moreover, receiver operating characteristic (ROC) analysis of derived CBC parameters (NLR, d-NLR, and platelet‐to-lymphocyte ratio [PLR] with disease severity and disease outcome) revealed d-NLR as better predictive marker of disease severity (area under the curve [AUC] = 0.658) and disease outcome (AUC = 0.766) compared to PLR with disease severity (AUC = 0.645) and disease outcome (AUC = 0.693). Conclusion: We therefore conclude, of the CBC parameters neutrophilia as the marker of disease severity and among derived parameters, d-NLR as an early predictive biomarker of both disease severity and poor disease outcome in SARS-CoV-2 patients. [ABSTRACT FROM AUTHOR]

The identification of patients with poor prognosis and early detection of COVID-19 disease complications are made possible by pathological analyses of routine hematological, coagulation, and biochemical tests. Interpreting analyses needs to be done within the framework of each patient’s unique clinical picture. It’s also critical to keep an eye on changes at the individual parameter level. From May 20th, 2021, to March 30th, 2024, a comprehensive search of literature was carried out using international databases, such as PubMed, Embase, Web of Science, Scopus, and the Cochrane Library, in compliance with the PRISMA guidelines. The research question was formulated using the PICO strategy. The following terms were used: biochemical parameters in COVID-19, hematological parameters in COVID-19, blood coagulation parameters in COVID-19, indicators of inflammation, and indicators of tissue damage in SARS-CoV-2. Routine hematological, coagulation, and biochemical tests are primarily used to monitor the progression of the disease and the effectiveness of treatment rather than being utilized for the established diagnosis of COVID-19 due to their low specificity. Molecular genetics and immunological techniques should be used to determine the COVID-19 disease diagnosis.

Inhibition of p38 mitogen-activated protein kinase (MAPKs) is a potential therapeutic approach for the treatment of acute and chronic pulmonary inflammatory conditions. Here, we report the in vitro and in vivo characterization of the anti-inflammatory effects of CHF6297, a novel potent and selective p38α inhibitor designed for inhalation delivery as a dry powder formulation. CHF6297 has been proven to inhibit p38α enzymatic activity with sub-nanomolar potency (IC50 = 0.14 ± 0.06 nM), with >1,000-fold selectivity against p38γ and p38δ. In human peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharides (LPS), as well as in human bronchial epithelial cells (BEAS2B) stimulated with TNF-α or cigarette smoke extract (CSE), CHF6297 inhibited interleukin (IL)-8 release with low nanomolar potency. CHF6297 administered to rats by using a nose-only inhalation device as a micronized dry powder formulation blended with lactose dose-dependently inhibited the LPS-induced neutrophil influx in the bronchoalveolar lavage fluid (BALF). CHF6297 administered intratracheally to rats dose-dependently counteracted the IL-1β (0.3 mg/kg)-induced neutrophil influx (ED50 = 0.22 mg/kg) and increase in IL-6 levels (ED50 = 0.82 mg/kg) in the BALF. In mice exposed to tobacco smoke (TS), CHF6297, administered intranasally (i.n.) for 4 days at 0.03 or 0.3 mg/kg, dose-dependently inhibited the corticosteroid-resistant TS-induced neutrophil influx in the BALF. In a murine house dust mite (HDM) model of asthma exacerbated by influenza virus A (IAV) (H3N3), CHF6297 (0.1 mg/kg, i.n.) significantly decreased airway neutrophilia compared to vehicle-treated IAV/HDM-challenged mice. When CHF6297, at a dose ineffective per se (0.03 mg/kg), was added to budesonide, it augmented the anti-inflammatory effects of the steroid. Overall, CHF6297 effectively counteracted lung inflammation in experimental models where corticosteroids exhibit limited anti-inflammatory activity, suggesting a potential for the treatment of acute exacerbations associated with chronic obstructive pulmonary disease (COPD) and asthma, acute lung injury (ALI), and viral-induced hyperinflammation.

Abstract Background Severe asthma is associated with substantial mortality and has unmet therapeutic need. A subset of severe asthma is characterized by neutrophilic airway inflammation. Classically activated (or M1) macrophages which express IL-12 and IL-23 are associated with airway neutrophilia in asthma. Exogenous IL-25 was reported to suppress intestinal inflammation in animal models of inflammatory bowel diseases via suppressing IL-12 and IL-23 production. We hypothesize that IL-25 ameliorates airway neutrophilia via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma. Methods In a mouse model of neutrophil-dominant allergic airway inflammation, the effect of mouse recombinant IL-25 on airway inflammation were assessed by H&E staining and bronchoalveolar lavage (BAL) cell counting. The percentage of M1 macrophages in lung tissue and BAL cells were analyzed by flow cytometry. Quantitative PCR and immunostaining were performed to measure the expression of Il12, Il23, and inflammatory cytokines. Mechanistic experiments were performed in primary culture of macrophages from mouse lungs. The expression of IL-12, IL-23 and IL-25 in sputum was analyzed in a cohort of severe asthma and subjects with eosinophilic or non-eosinophilic asthma. Results Intranasal administration of IL-25 markedly decreased the number of neutrophils in BAL cells in a murine model of neutrophil-dominant allergic airway inflammation. Moreover, exogenous IL-25 decreased the number of M1 macrophages, and reduced the expression of IL-12, IL-23 in the lungs of the mouse model. Exogenous IL-25 also inhibited the expression of inflammatory cytokines IL-1β, IFN-γ, TNF-α and IL-17 A. In vitro, IL-25 suppressed IL-12 and IL-23 expression in lipopolysaccharide (LPS)-stimulated primary culture of mouse pulmonary macrophages. Mechanistically, IL-25 inhibited LPS-induced c-Rel translocation to nucleus via STAT3-dependent signaling. In a cohort of severe asthma, IL-25 protein levels in sputum were significantly lower than control subjects. The transcript levels of IL-12 and IL-23 were increased whereas IL-25 transcripts were decreased in sputum cells from subjects with non-eosinophilic asthma compared to eosinophilic asthma. Conclusions IL-25 expression is downregulated in subjects with severe or non-eosinophilic asthma. Exogenous IL-25 ameliorates airway neutrophilia, at least in part, via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23.

Abstract A farm in North-West Germany experienced a high morbidity and mortality in their sow herd. Sows showed fever, lethargy, oedema, mucosal discharge and dyspnoea. Necropsy revealed a severe fibrinous and purulent polyserositis. Haematological and histological examinations confirmed septicaemia. Streptococcus equi subspecies zooepidemicus was isolated in high yields from major organs. Sequence typing of this isolate (21/455) revealed a new sequence type showing a significantly higher proliferation rate in comparison to two other isolates. Other infectious agents (influenza A virus, Porcine Reproductive and Respiratory Syndrome Virus, Porcine Circovirus 2, african swine fever virus, classical swine fever virus, Actinobacillus pleuropneumoniae) were excluded by routine diagnostic examinations. A climate check revealed an insufficient air supply in the area for the gestating sows. This case describes the first disease outbreak in swine due to S. zooepidemicus in Germany.

Background: Severe asthma is associated with substantial mortality and has unmet therapeutic need. A subset of severe asthma is characterized by neutrophilic airway inflammation. Classically activated (or M1) macrophages which express IL-12 and IL-23 are associated with airway neutrophilia in asthma. Exogenous IL-25 was reported to suppress intestinal inflammation in animal models of inflammatory bowel diseases via suppressing IL-12 and IL-23 production. We hypothesize that IL-25 ameliorates airway neutrophilia via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23 in asthma. Methods: In a mouse model of neutrophil-dominant allergic airway inflammation, the effect of mouse recombinant IL-25 on airway inflammation were assessed by H&E staining and bronchoalveolar lavage (BAL) cell counting. The percentage of M1 macrophages in lung tissue and BAL cells were analyzed by flow cytometry. Quantitative PCR and immunostaining were performed to measure the expression of Il12, Il23, and inflammatory cytokines. Mechanistic experiments were performed in primary culture of macrophages from mouse lungs. The expression of IL-12, IL-23 and IL-25 in sputum was analyzed in a cohort of severe asthma and subjects with eosinophilic or non-eosinophilic asthma. Results: Intranasal administration of IL-25 markedly decreased the number of neutrophils in BAL cells in a murine model of neutrophil-dominant allergic airway inflammation. Moreover, exogenous IL-25 decreased the number of M1 macrophages, and reduced the expression of IL-12, IL-23 in the lungs of the mouse model. Exogenous IL-25 also inhibited the expression of inflammatory cytokines IL-1β, IFN-γ, TNF-α and IL-17 A. In vitro, IL-25 suppressed IL-12 and IL-23 expression in lipopolysaccharide (LPS)-stimulated primary culture of mouse pulmonary macrophages. Mechanistically, IL-25 inhibited LPS-induced c-Rel translocation to nucleus via STAT3-dependent signaling. In a cohort of severe asthma, IL-25 protein levels in sputum were significantly lower than control subjects. The transcript levels of IL-12 and IL-23 were increased whereas IL-25 transcripts were decreased in sputum cells from subjects with non-eosinophilic asthma compared to eosinophilic asthma. Conclusions: IL-25 expression is downregulated in subjects with severe or non-eosinophilic asthma. Exogenous IL-25 ameliorates airway neutrophilia, at least in part, via inhibiting macrophage M1 polarization and the expression of IL-12 and IL-23. [ABSTRACT FROM AUTHOR]

A farm in North-West Germany experienced a high morbidity and mortality in their sow herd. Sows showed fever, lethargy, oedema, mucosal discharge and dyspnoea. Necropsy revealed a severe fibrinous and purulent polyserositis. Haematological and histological examinations confirmed septicaemia. Streptococcus equi subspecies zooepidemicus was isolated in high yields from major organs. Sequence typing of this isolate (21/455) revealed a new sequence type showing a significantly higher proliferation rate in comparison to two other isolates. Other infectious agents (influenza A virus, Porcine Reproductive and Respiratory Syndrome Virus, Porcine Circovirus 2, african swine fever virus, classical swine fever virus, Actinobacillus pleuropneumoniae) were excluded by routine diagnostic examinations. A climate check revealed an insufficient air supply in the area for the gestating sows. This case describes the first disease outbreak in swine due to S. zooepidemicus in Germany. [ABSTRACT FROM AUTHOR]

Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA‐approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases. Synopsis: Deregulation of inflammasome activity contributes to hematopoietic alterations associated to chronic inflammatory diseases, including neutrophilia and anemia. Zebrafish models and human blood cells were used to identify the critical role of the NLRP1 inflammasome on the regulation of hematopoiesis and possible therapeutic targets for clinical intervention.Erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis.ZAKα/P38 kinase axis phosphorylated and promoted the assembly of NLRP1 in HSPCs which, in turn, regulates their erythroid‐myeloid lineage decision.NLRP1 inflammasome in HSPCs was inhibited by LRRFIP1 and FLII, independently of DPP9.The FDA/EMA‐approved drug Nilotinib inhibited NLRP1 inflammasome activation alleviating neutrophilia and promoting erythroid differentiation. [ABSTRACT FROM AUTHOR]

The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO2 and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO2 have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO2; nano-sized dust has a greater number of particles and a larger total particle--cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophildriven lung pathogenesis explains why dust exposure induces more severe lesions in rats than hamsters; why, on a mass-dose basis, nano-sized dusts are more toxic than the micron-sized dusts; why lung lesions progress with time; and why dose--response curves of particle toxicity exhibit a hockey stick like shape with a threshold. The neutrophil centric AOP for particle-induced lung disease has implications for risk assessment of human exposures to dust particles and environmental particulate matter. [ABSTRACT FROM AUTHOR]

The correction notice in the journal "Frontiers in Pharmacology" addresses an error in Figure 1 of the article titled "CHF6297: a novel potent and selective p38 MAPK inhibitor with robust anti-inflammatory activity and suitable for inhaled pulmonary administration as dry powder." The chemical structures in the figure were inaccurate, but this correction does not impact the scientific conclusions of the article. The authors have provided the corrected Figure 1, and the original article has been updated accordingly. [Extracted from the article]

Abstract Chronic inflammatory diseases are associated with hematopoietic lineage bias, including neutrophilia and anemia. We have recently identified that the canonical inflammasome mediates the cleavage of the master erythroid transcription factor GATA1 in hematopoietic stem and progenitor cells (HSPCs). We report here that genetic inhibition of Nlrp1 resulted in reduced number of neutrophils and increased erythrocyte counts in zebrafish larvae. We also found that the NLRP1 inflammasome in human cells was inhibited by LRRFIP1 and FLII, independently of DPP9, and both inhibitors regulated hematopoiesis. Mechanistically, erythroid differentiation resulted in ribosomal stress‐induced activation of the ZAKα/P38 kinase axis which, in turn, phosphorylated and promoted the assembly of NLRP1 in both zebrafish and human. Finally, inhibition of Zaka with the FDA/EMA‐approved drug Nilotinib alleviated neutrophilia in a zebrafish model of neutrophilic inflammation and promoted erythroid differentiation and GATA1 accumulation in K562 cells. In conclusion, our results reveal that the NLRP1 inflammasome regulates hematopoiesis and pave the way to develop novel therapeutic strategies for the treatment of hematopoietic alterations associated with chronic inflammatory and rare diseases.

Solomon Getawa, Biruk Bayleyegn Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Solomon Getawa, Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, P.O.Box: 196, Gondar, Ethiopia, Tel +251-914-665-736, Email solomon2525geta@gmail.comBackground: Heart failure pathophysiology and its clinical symptoms are characterized by inflammation. Elevated levels of leukocyte subpopulations are a well-known indicator of inflammation and play a predictive role in determining the prognosis of patients with cardiovascular diseases. Besides, platelets are essential mediators of inflammation, especially when they interact with leukocytes. Platelet synthesis, activation, and function are all impacted by heart failure. Thus, the study was aimed at determining the magnitude of platelet, neutrophil, and lymphocyte abnormalities in patients with heart failure.Methods: A retrospective cross-sectional study was conducted from June to July 2022 at the University of Gondar comprehensive specialized hospital. A total of 245 medical records of heart failure patients were included. Data regarding socio-demographic, clinical, and some hematological and biochemical parameters were collected from medical records. Data was entered into Epi-Data 4.6.0.2 and then exported to Stata 11.0 statistical software for analysis. A binary logistic regression analysis with its odds ratio was calculated to identify factors associated with the outcome variables. P-value < 0.05 was considered statistically significant.Results: The most frequent leukocyte abnormality among adults with heart failure was neutrophilia, which was detected in 17.55% (95% CI: 13.26– 22.87). Besides, lymphocytosis was observed in 10.20% (95% CI: 6.97– 14.70) of patients. The magnitude of thrombocytopenia and thrombocytosis among patients with heart failure was 12.24% (95% CI: 8.67– 17.01%) and 2.86% (95% CI: 1.36– 5.90%), respectively. Only being female was significantly associated with neutrophilia in patients with heart failure (AOR = 2.33; 95% CI: 1.05– 5.16). However, none of the variables were significantly associated with platelet and lymphocyte abnormalities.Conclusion: Neutrophilia, lymphocytosis, and thrombocytopenia are the common leukocyte and platelet abnormalities in heart failure patients. Therefore, early detection and management of the underlying causes of those abnormalities may be important to improve patients’ outcomes and prevent further complications.Keywords: heart failure, platelet, neutrophil, lymphocyte, neutrophilia, lymphocytosis, thrombocytopenia

Abstract Background There have been suggestions that hematologic abnormalities in COVID-19 are linked with the progression and severity of diseases and mortality. Lymphopenia, sepsis, and thrombocytopenia were highly reported in patients with COVID-19. This study investigated the significance of hematologic abnormalities in patients with COVID-19 in Lagos, Nigeria, and its potential as a diagnostic tool for COVID-19 severity. Results This was a retrospective observational study with a total of 340 patients with COVID-19 (236 patients included in the analysis). These patients were categorized into two groups, comprising 71 patients with severe COVID-19 (SCP) and 165 patients with non-severe COVID-19 (NSCP). The majority were males in both categories (SCP 74.6% and NSCP 63.6%). The mean ± SD ages for SCP and NSCP were 52.28 ± 16.87 and 42.44 ± 17.18 years, respectively. The SCP (52.1%) and NSCP (20.0%) had underlying health conditions. The SCP exhibited significantly higher neutrophil counts (P

A 6-year-old girl presented with recurrent skin rash at the initial stage, recent joint pain, and neutrophilia was found during a routine blood test. After a multidisciplinary case discussion, she was diagnosed with chronic neutrophil leukemia, and the symptoms were relieved after hydroxyurea and luxolitinib treatment. She received the allogeneic hematopoietic stem cell transplantation subsequently. At present, she is in stable condition and under follow-up. Chronic neutrophil leukemia is a rare disease, which rarely occurs in children. It is more difficult to diagnose in patients with skin rash as the first manifestation. The diagnosis and treatment of this case reflects the important role of multidisciplinary cooperation in the diagnosis and treatment of difficult and rare diseases.

Background: Diaphragmatic hernia is an emerging threat in dairy animals due to accidental ingestion of potential foreign body via feed or fodder leads to traumatic reticulo pericarditis and net results into loss of milk production. Loss of milk production due to diaphragmatic hernia in dairy animals is worrying situation among the milkman and it needs to be addressed in early stage. Considering the livelihood of poor to marginal farmers on dairy animals, the present study aimed to evaluate the clinico-haematological changes and surgical management of diaphragmatic hernia in cattle and buffalo. Methods: The present retrospective study was carried in thirty two clinical cases of diaphragmatic hernia in cattle (17) and buffaloes (15) presented to teaching veterinary clinical complex from the rural area irrespective breeds, age and no. of lactation of animals. Result: The incidence was higher in recently parturited followed by advanced pregnant animals aged between 3.5-14 years (7.109±0.406) with duration of illness ranged between 4-35 days (16.563±1.627). All animals showed recurrent tympany, suspended rumination, constipation, neutrophilia, alkaline ruminal pH, lymphopenia and increased level of muscle enzymes and non-responsive to medicinal therapy. Plain radiography of thoraco-abdominal region showed break in continuity of diaphragmatic line and herniation of reticulum into thoracic cavity. All animals were subjected to surgical correction of diaphragmatic hernia under isoflurane general anaesthesia. Out of 32, 27 animals were recovered uneventfully and remaining five animals were succumbed during surgical repair of hernia due to cardiovascular failure. The present study concludes that, diaphragmatic hernia is common wasting disorders in dairy animals characterized by scanty faeces, recurrent tympany, neutrophilia, increased level of muscle enzymes due to chronic inflammatory changes and it can be treated successfully with herniorrhaphy under isoflurane general anaesthesia. [ABSTRACT FROM AUTHOR]

A 9‐year‐old female spayed Boston Terrier presented for diagnostic investigation of lethargy, poor appetite, weight loss, and a marked leukocytosis. Significant muscle wasting and a palpable abdominal mass were present on physical examination. Abdominal imaging revealed the mass to be of small intestinal origin; consequently, an intestinal resection and anastomosis were performed without complication. The histopathologic diagnosis was a gastrointestinal stromal tumor, verified by immunohistochemical positivity to CD117 (KIT). Two weeks after discharge, the leukocytosis had resolved. Though the exact molecular mediator of the severe leukocytosis was undetermined, resolution following tumor removal suggests a paraneoplastic cause. To the authors' knowledge, this is the first reported case of probable paraneoplastic leukocytosis secondary to a gastrointestinal stromal tumor in the dog. Gastrointestinal tract imaging should be performed when this uncommon hematologic abnormality is present. [ABSTRACT FROM AUTHOR]

Abstract Background Asthma is a chronic inflammatory disease that affects the lungs. Variation in whole blood cell lines is caused by the progression and severity of asthma. Common hematological abnormalities encountered during asthma include eosinophilia, neutrophilia, leukocytosis, and increased erythrocyte sedimentation rate. The main aim of this study was to assess the selected hematological abnormalities and their associated factors among asthmatic patients in Northwest Ethiopia from March to May 2021. Methodology A hospital-based cross-sectional study was conducted on a total of 320 asthmatic patients in Northwest Ethiopia. A simple random sampling technique was employed to select study participants. A pre-tested structured questionnaire and a checklist were used to collect data. Blood samples were collected from asthmatic patients for complete blood count and erythrocyte sedimentation rate determination. Hematological profiles were analyzed by Unicel DxH 800 (Beckman Coulter, Ireland). The erythrocyte sedimentation rate was determined by using the Westergren method. The data were entered into EpiData version 3.0.4 and analyzed with a statistical package for social science version 20 software. The bi-variable and multi-variable binary logistic regression models were used to assess the factors associated with hematological abnormalities. A p value of less than 0.05 in the multivariable logistic regression analysis was considered statistically significant. Results The overall prevalence of neutrophilia, eosinophilia, thrombocytopenia, leukocytosis, and basophilia was 35.3%, 20%, 11.9%, 10.3%, and 4.1%, respectively. Neutrophilia was associated with a lack of physical activity (AOR = 3.25; 95% CI 1.43–7.37) and a history of taking non-asthmatic drugs within the previous three months (AOR = 2.63; 95% CI 1.22–5.65). Being admitted to the emergency department (AOR = 0.27; 95% CI 0.11–5.67) was found to be associated with eosinophilia. In addition, being admitted to the emergency department (AOR = 5.44; 95%CI: 2.6–11.3) was associated with thrombocytopenia. Conclusion The current study demonstrated the predominant prevalence of neutrophilia, followed by eosinophilia, among asthma patients. Therefore, hematological abnormalities should be taken into account for proper monitoring and management of asthmatic patients.

Background: Hyperglycemic patients are at a high risk of COVID-19 severity. Neutrophils have been considered critical effector cells in COVID-19 development. Vitamin D deficiency is prevalent in hyperglycemic patients and was found to adversely associate with the neutrophil count. Aim: The goal of this work was to evaluate the characteristics of diabetic and pre-diabetic COVID-19 patients and discovered changes in neutrophils and their correlation, if any, with disease clinical presentation. Patients and Methods: The study included total of (514) Covid-19 positive patients confirmed by PCR and recruited from the Prince Mohammad Bin Abdulaziz Hospital in Riyadh, Saudi Arabia. Patient's clinical characteristics were collected for all patients. Laboratory tests include HbA1c, neutrophil count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, D- dimer, 25 hydroxy vitamin D (25(OH)D), and folate. Results: The results found that 286 patients (55.6%) were diabetic, 77 patients (15%) were pre-diabetic and 151 (29.4%) were normoglycaemic. A significant difference was exhibited regarding the neutrophil count and inflammatory factors of COVID-19 severity. Furthermore, the neutrophil count was found to be directly correlated with the severity monitoring biochemical markers for Covid-19: CRP, ESR, ferritin, and D-dimer and inversely associated with vitamin D levels in diabetic and pre-diabetic patients. Conclusion: Our findings highlight the change of neutrophils in COVID-19 diabetic and pre-diabetic patients that was found to correlate positively with CRP, ESR, ferritin, and D-dimer, and negatively with 25(OH)D, but their correlation with the clinical presentation of the disease need further large investigations. [ABSTRACT FROM AUTHOR]

Gentamicin (GM) is an aminoglycoside antibiotic that induces nephrotoxicity. GM also causes necrosis of cells in the renal proximal tubules, resulting in acute tubular necrosis, followed by acute renal failure. Morphological alteration of blood cells, leukocytes and platelets count, as well as biochemical effects of l-cysteine (Cys) and antibiotic gentamicin, in clinically healthy male Wistar rats, were studied. Rats were divided into four groups: control (injected with 0.9% saline i.p.), GM (80 mg/kg b.w.; gentamicin injected i.p.), Cys-GM (100 mg/kg b.w.; l-cysteine and 80 mg/kg b.w. gentamicin injected i.p.), and Cys-GM-Cys (administered double dosage of 100 mg/kg b.w. l-cysteine and 80 mg/kg b.w. gentamicin i.p.). Biochemical and hematological analyses were performed on blood samples taken six days after treatments. Total proteins, albumin concentration and A/G ratio were significantly lower in experimental groups. Cholesterol, triglycerides, urea, and creatinine concentrations were significantly higher in relation to control. GM-induced lymphocytopenia, thrombocytopenia and neutrophilia. Echinocytosis and platelet disaggregation were found in all GM-treated animals. GM caused renal injury which indirectly led to erythrocyte abnormalities, changes in platelet aggregation, decreased protein fractions, and increased lipid and nitrogen components. The results suggest that GM-induced renal injury leads to significant biochemical changes in blood plasma, erythrocyte membrane impairment which can consequently cause anemia. Therefore, Cys might represent a novel therapeutic tool in the prevention and treatment of gentamicin-induced renal injury and blood cell disorders. [ABSTRACT FROM AUTHOR]

Aims Diagnosis of Adenotonsillar Hypertrophy (ATH), the leading cause of pediatric Obstructive Sleep Apnea (OSA), depends on physical exam via Brodsky's staging of tonsils. This study investigates the associations of ATH with patient parameters, and balances in-office tonsil hypertrophy appraisal against true organ mass. Materials and Methods A prospective cohort was formed of 103 children operated for ATH, and 31 matched controls. Demographic, clinical and tympanographic data, as well as Complete Blood Count (CBC) indices were compared. Absolute and relative to total body weight tonsil specimen mass were correlated with Brodsky's score. Results Tonsillar size indices were significantly raised in ATH patients. Elevated leukocytes (P = 0.012) and increased neutrophil percentage (P = 0.025) conveyed higher ATH risk. Subjective evaluation of tonsils graded 1 or 2 correlated significantly with absolute (P = 0.001) and relative (P = 0.006) objective measurements. Brodsky's score 3 and 4 displayed marginal significant association with relative (P = 0.050) but not with true (P = 0.989) mass. Conclusion An occult hematologic inflammatory response was detected in ATH children. Clinical estimation of severely hypertrophic tonsils should be adjusted for total body weight. Trial Registration Number: NCT03541434 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: There have been suggestions that hematologic abnormalities in COVID-19 are linked with the progression and severity of diseases and mortality. Lymphopenia, sepsis, and thrombocytopenia were highly reported in patients with COVID-19. This study investigated the significance of hematologic abnormalities in patients with COVID-19 in Lagos, Nigeria, and its potential as a diagnostic tool for COVID-19 severity. Results: This was a retrospective observational study with a total of 340 patients with COVID-19 (236 patients included in the analysis). These patients were categorized into two groups, comprising 71 patients with severe COVID-19 (SCP) and 165 patients with non-severe COVID-19 (NSCP). The majority were males in both categories (SCP 74.6% and NSCP 63.6%). The mean ± SD ages for SCP and NSCP were 52.28 ± 16.87 and 42.44 ± 17.18 years, respectively. The SCP (52.1%) and NSCP (20.0%) had underlying health conditions. The SCP exhibited significantly higher neutrophil counts (P < 0.05) and significantly lower mean hemoglobin, red blood cell (RBC), packed cell volume (PCV), and lymphocyte values (P < 0.05). Anemia and lymphocytopenia were more prominent in the SCP group than in the NSCP group (P < 0.05). Hemoglobin, RBC, PCV, and lymphocytes were inversely correlated with age-group in the SCP, while only lymphocytes and platelets were inversely correlated with age-group in the NSCP. The highest area under the ROC curve (AUC) for neutrophils was 0.739 with a sensitivity of 62.0% and specificity of 80.0%, while white blood cells had an AUC of 0.722 with a sensitivity of 73.2% and specificity of 61.2%. The AUC for neutrophil–lymphocyte ratio (NLR) was 0.766 with a sensitivity of 63.3% and specificity of 83.5%, while that for the platelet–lymphocyte ratio (PLR) was 0.695 with a sensitivity and specificity of 61.7% and 77.8%. Conclusions: COVID-19 affected the levels of hemoglobin, RBC, PCV, and lymphocytes in the blood, and the differences were significant between the SCP and NSCP. The significant changes in neutrophil and lymphocyte counts may be useful in the prognosis and management of COVID-19 severity in hospital settings. Furthermore, NLR and PLR may be used in the prognosis and management of severe COVID-19 infection, as well as provide an objective basis for early identification and management in low-resource settings. [ABSTRACT FROM AUTHOR]

• MPO deficiency is a risk factor for inflammation-induced neutrophilia and anemia. • MPO deficiency leads to increased granulopoiesis and decreased erythropoiesis. • Neutrophil-derived G-CSF may play a critical role in the increased granulopoiesis. • MPO deficiency enhances IKKβ/NF-κB-dependent G-CSF production from neutrophils. We previously reported that myeloperoxidase-deficient (MPO-/-) mice develop more severe neutrophil-rich lung inflammation than wild-type mice following intranasal Zymosan administration. Interestingly, we found that these mutant mice with severe lung inflammation also displayed pronounced neutrophilia and anemia, characterized by increased granulopoiesis and decreased erythropoiesis in the bone marrow, compared to wild-type mice. This condition was associated with higher concentrations of granulocyte-colony stimulating factor (G-CSF) in both the lungs and serum, a factor known to enhance granulopoiesis. Neutrophils accumulating in the lungs of MPO-/- mice produced greater amounts of G-CSF than those in wild-type mice, indicating that they are a significant source of G-CSF. In vitro experiments using signal transduction inhibitors and Western blot analysis revealed that MPO-/- neutrophils express higher levels of G-CSF mRNA in response to Zymosan, attributed to the upregulation of the IκB kinase/nuclear factor (NF)-κB pathway and the extracellular-signal-regulated kinase/NF-κB pathway. These findings highlight MPO as a critical regulator of granulopoiesis and erythropoiesis in inflamed tissues. [ABSTRACT FROM AUTHOR]

The unanticipated outbreak of the COVID-19 pandemic has shocked the world in terms of both lives and livelihood. SARS-CoV-2 virus primarily affects the respiratory system, although other organ systems are also involved. Early diagnosis followed up by a retrospective analysis and tracking of a few markers relevant to the immunological status of the individual may aid in determining the state of the patient's disease prognosis. The aim of the present study was to evaluate immunological parameters such as neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), and D-dimer, taking into account the patient's age and oxygen saturation level. Our retrospective analysis of clinical data revealed that such parameters as CRP, D-dimer, and NLR should be taken into consideration to predict severe COVID-19-related complications. The data obtained indicate that patients over age 60 are especially vulnerable to severe COVID-19.

Natalia Troianova,1,&ast; Barbara Mariotti,1,&ast; Valentina Micheletti,2,3 Federica Calzetti,1 Marta Donini,1 Gianluca Salvagno,4,5 Marcello Ferrari,2,3 Ernesto Crisafulli,2,3 Flavia Bazzoni1 1Department of Medicine, Division of General Pathology, University of Verona, Verona, Italy; 2Department of Medicine, Respiratory Medicine Unit, University of Verona and Verona University Hospital, Verona, Italy; 3Department of Medicine, Section of Internal Medicine, University of Verona and Verona University Hospital, Verona, Italy; 4Section of Clinical Biochemistry, University Hospital of Verona, Verona, Italy; 5Service of Laboratory Medicine, Pederzoli Hospital, Peschiera del Garda, Italy&ast;These authors contributed equally to this workCorrespondence: Flavia BazzoniDepartment of Medicine, Division of General Pathology University of Verona, Strada le Grazie 8, Verona, 37134, ItalyTel +39 045 8027128Email flavia.bazzoni@univr.itPurpose: Chronic obstructive pulmonary disease is characterized by chronic inflammatory response both at the lung site and at the systemic level. Abnormalities in circulating leukocytes have been reported to occur in COPD patients and have been often shown to correlate with the decline in lung function. COPD affects men and women at a virtually comparable rate, even though distinct sex specific symptoms, progression and therapeutic implications have been described. Nonetheless, these sex-associated differences have not been analyzed in terms of circulating leukocytes. To assess the impact of sex on the changes of circulating immune cells in COPD patients.Patients and Methods: Blood samples were collected from 50 COPD patients (31 males, 19 females) and 63 age and sex-matched controls (35 males, 28 females) enrolled in this pilot study. Complete blood cell count and multi-parametric flow cytometry analysis were performed to characterize the leukocyte populations and subsets.Results: Male COPD patients are distinguished from controls by a significant increase in white blood cell counts, neutrophil total and differential counts, and neutrophil-to-lymphocyte ratio. Conversely, a generalized leukocyte decrease discriminated female COPD patients from the related controls. The impact of sex is further remarked by a decrease in adaptive immune cell subpopulations in males as opposed to a consistent increase of innate immune cell types in females correlating with disease severity.Conclusion: These data indicate that the definition of specific changes of circulating leukocytes to be used as reliable biomarkers of the disease severity cannot be accomplished irrespectively of sex.Keywords: sex, COPD, blood leukocytes, neutrophil-to-lymphocyte ratio, neutrophilia

Background: Cerebrospinal fluid (CSF) is commonly analyzed in South American camelids with suspected neurologic disease because of ease of collection and characteristic findings associated with certain diseases. Objectives: To assess CSF findings associated with short‐term survival or non‐survival in South American camelids in which neurologic disease was a differential diagnosis based on history and physical examination. Animals: Twenty‐one llamas and 33 alpacas that underwent CSF analysis at the University of Missouri Veterinary Health Center. Methods: Retrospective study. Medical records of camelids that underwent CSF analysis between January 2005 and September 2021 were studied. Short‐term survival was defined as survival to discharge from the Veterinary Health Center. A Fisher's exact test was used to compare species, CSF results, and survival. Results: Odds of survival were 3.9 times higher in camelids with a total nucleated cell count (TNCC) <3 cells/μL (P =.04). No significant association was found between survival and total protein concentration (TPC; P =.15) or percentage of eosinophils (P = 1.0). No significant correlation was found between species and increased TNCC (P =.63), TPC (P =.55), or percentage of eosinophils (P =.30). Among camelids diagnosed with Paralephostrongylus tenuis infestation, odds of survival were 4.95 times higher in alpacas (P =.05). Conclusions: Cerebrospinal fluid TNCC ≥3 cells/μL is associated with decreased odds of short‐term survival in South American camelids. [ABSTRACT FROM AUTHOR]

Background and Aims: In patients with acutely decompensated cirrhosis (ADC) who present with clinically apparent precipitants (i.e., infections, acute liver injury), alterations in blood markers of inflammation associate with progression toward severe phenotypes (e.g., acute-on-chronic liver failure, ACLF). It is unclear whether alterations in blood inflammatory markers may associate with progression of ADC independently of precipitants., Methods: We prospectively enrolled 394 patients admitted for ADC who were classified into four phenotypes of increasing severity: no organ dysfunction (n=168), organ dysfunction alone (n=72), organ failure without ACLF (n=91), and ACLF (n=63). Clinical blood cell counts and serum levels of inflammatory markers (including soluble markers related to type-1, type-2, and type-3 inflammation) were obtained at enrollment. Ordinal regression with adjacent categories logit model adjusted for confounders (including precipitants) was used to analyze associations between changes in each blood inflammatory marker and the worsening of ADC., Results: Inflammatory markers that were associated with higher risk of progressing to the next more severe stage were as follows: increasing neutrophil counts (adjusted common odds ratio [cOR] 1.17, 95%CI 1.06-1.28); increasing levels of the type-2 cytokine interleukin (IL)-25 (cOR 1.21, 95%CI 1.06-1.39), type-3 cytokines IL-6 (cOR 1.15, 95%CI 1.02-1.28) and IL-22 (cOR 1.16, 95%CI 1.03-1.30), or anti-inflammatory soluble CD163 (cOR 1.94, 95%CI 1.58-2.38); decreasing lymphocyte counts (cOR 0.77, 95%CI 0.68-0.87), or decreasing levels of the type-1 cytokine IFN-γ (cOR 0.85, 95%CI 0.75-0.95)., Conclusions: Among patients with ADC, alterations in blood levels of cytokines related to type-1, type-2 and type-3 inflammation, together with neutrophilia, lymphopenia and elevated anti-inflammatory signals were individually associated with an increased risk of progressing toward ACLF, independently of the presence of clinically apparent precipitants., (Copyright © 2024. Published by Elsevier B.V.)

The objective of this study was to determine the extent that nebulized glycosylated caffeic acid phenylether ester-4-O-alpha-D-glucopyranoside (G-CAPE) attenuates particulate-induced airway inflammation in healthy horses. Our hypothesis was that nebulization with G-CAPE would result in improved respiratory scores, higher arterial oxygen partial pressure, and less inflammatory airway infiltrates in horses with induced airway inflammation, compared with untreated controls. Five healthy adult horses were housed inside a climate controlled, closed barn on straw bedding and fed ad lib moldy grass hay for 16 days to induce airway inflammation. An experimental crossover study was performed in which animals were treated with 200 mg G-CAPE dissolved in 45 mL of 10% triethanolamine (G-CAPE group) or 45 mL of 10% triethanolamine (CONTROL group), and clinical respiratory scoring, arterial blood gases, and bronchoalveolar lavages (BALs) were collected at predetermined time points up to 24 h post nebulization. While the mean neutrophil percentage decreased in treated horses compared to controls (9.3 ± 2.0 and 16.9 ± 2.4, respectively) at 6 hours post treatment (t = 6 h), the difference did not achieve statistical significance (p = 0.1154). Blood gas analysis did not differ significantly between groups. There was a significant difference in the mean respiratory scores of G-CAPE-treated horses between baseline and at 1-h post treatment (from 3.2 ± 0.7 to 1.6 ± 0.7, p = 0.0013). This study demonstrates that a single nebulized dose of G-CAPE decreased clinical respiratory scores 1 h post administration and decreased BAL percentage of neutrophils 6 h post administration in horses with particulate induced airway inflammation. This compound shows promise as an anti-inflammatory and warrants further investigation.

IntroductionPoor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival.MethodsA cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables.ResultsMultivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival.ConclusionNeutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.

SARS-CoV-2 is a systemic infection that has a significant impact on the hemostasis and hematopoietic system. Lymphopenia may be considered a cardinal laboratory finding, with prognostic potential. The study aimed to determine the differential leukocyte count in SARSCoV-2 among Sudanese patients, during the period from March to December 2020. A total of 787 subjects were enrolled 487 patients with COVID-19 and 300 healthy volunteers as a control group; their ages ranged from 29 to 89 years. 3 ml of EDTA venous blood samples were collected from each participant standard for CBC investigation and then analyzed by SPSS version 21 (Mean and Standard deviation). A significant association between leukocyte count among ICU, ER group, and control with (P. value 0.000), in addition, a significant association was revealed among mild group and control group in differential neutrophil count, differential lymphocyte count, and absolute neutrophil count (p. value 0.000), however non-significant in TWBC absolute mixed cell count, absolute lymphocyte count, and differential mixed cells count (value 0.7,0.2, 0.19) respectively. The study concluded that leukocytosis with neutrophilia and lymphopenia is associated with the severity of SARS-CoV-2 infection, and should be implicated as predict for a serious course of the disease as well as mortality. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 is an infectious disease that was found at the end of 2019. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized as the virus that leads to COVID-19. The study was directed to find out the hematological parameter changes in COVID-19 patients according to the severity of the disease. Methods: The study has been done in two centers Sulaymaniyah and Duhok Governorates for a period of six months between September 2021 to March 2022. A total of 201 enrolled patients were included. For each patient demographic characteristics and blood test results (total and differential WBC, Hb, platelet, ferritin, CRP, D-dimer, NLR, PLR) were collected, following the severity of the disease and the outcome of each one of the patients. SPSS software was used for statistical analysis. Results: The study revealed that female patients were more than males 60.2% and 39.8% respectively with an overall mean age of 54.65±17 years. The mean duration of hospitalization is 14.4 ± 7.7 days. Furthermore, the study showed that patients had 30.8% leukocytosis,17.4% lymphopenia, and 31.8% neutrophilia. Higher NLR and PLT are seen in severe cases with NLR ≥3.1and PLR ≥ 285. Also, high levels of CRP, D-dimer, and ferritin were seen in severe COVID-19 patients. Conclusions: Changes in hematological parameters can be useful in predicting of the disease severity of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic inflammatory disease that affects the lungs. Variation in whole blood cell lines is caused by the progression and severity of asthma. Common hematological abnormalities encountered during asthma include eosinophilia, neutrophilia, leukocytosis, and increased erythrocyte sedimentation rate. The main aim of this study was to assess the selected hematological abnormalities and their associated factors among asthmatic patients in Northwest Ethiopia from March to May 2021.Methodology: A hospital-based cross-sectional study was conducted on a total of 320 asthmatic patients in Northwest Ethiopia. A simple random sampling technique was employed to select study participants. A pre-tested structured questionnaire and a checklist were used to collect data. Blood samples were collected from asthmatic patients for complete blood count and erythrocyte sedimentation rate determination. Hematological profiles were analyzed by Unicel DxH 800 (Beckman Coulter, Ireland). The erythrocyte sedimentation rate was determined by using the Westergren method. The data were entered into EpiData version 3.0.4 and analyzed with a statistical package for social science version 20 software. The bi-variable and multi-variable binary logistic regression models were used to assess the factors associated with hematological abnormalities. A p value of less than 0.05 in the multivariable logistic regression analysis was considered statistically significant.Results: The overall prevalence of neutrophilia, eosinophilia, thrombocytopenia, leukocytosis, and basophilia was 35.3%, 20%, 11.9%, 10.3%, and 4.1%, respectively. Neutrophilia was associated with a lack of physical activity (AOR = 3.25; 95% CI 1.43-7.37) and a history of taking non-asthmatic drugs within the previous three months (AOR = 2.63; 95% CI 1.22-5.65). Being admitted to the emergency department (AOR = 0.27; 95% CI 0.11-5.67) was found to be associated with eosinophilia. In addition, being admitted to the emergency department (AOR = 5.44; 95%CI: 2.6-11.3) was associated with thrombocytopenia.Conclusion: The current study demonstrated the predominant prevalence of neutrophilia, followed by eosinophilia, among asthma patients. Therefore, hematological abnormalities should be taken into account for proper monitoring and management of asthmatic patients. [ABSTRACT FROM AUTHOR]