ABSTRACT
Introduction: The main aim of this study was to assess the utility of differential white cell count and cell population data (CPD) for the detection of COVID-19 in patients admitted for community-acquired pneumonia (CAP) of different etiologies. Methods: This was a multicenter, observational, prospective study of adults aged ≥18 years admitted to three teaching hospitals in Spain from November 2019 to November 2021 with a diagnosis of CAP. At baseline, a Sysmex XN-20 analyzer was used to obtain detailed information related to the activation status and functional activity of white cells. Results: The sample was split into derivation and validation cohorts of 1065 and 717 patients, respectively. In the derivation cohort, COVID-19 was confirmed in 791 patients and ruled out in 274 patients, with mean ages of 62.13 (14.37) and 65.42 (16.62) years, respectively (p<0.001). There were significant differences in all CPD parameters except MO-Y. The multivariate prediction model showed that lower NE-X, NE-WY, LY-Z, LY-WY, MO-WX, MO-WY, and MO-Z values and neutrophil-to-lymphocyte ratio were related to COVID-19 etiology with an AUC of 0.819 (0.790, 0.846). No significant differences were found comparing this model to another including biomarkers (p=0.18). Conclusions: Abnormalities in white blood cell morphology based on a few cell population data values as well as NLR were able to accurately identify COVID-19 etiology. Moreover, systemic inflammation biomarkers currently used were unable to improve the predictive ability. We conclude that new peripheral blood biomarkers can help determine the etiology of CAP fast and inexpensively. (AU)
Subject(s)
Humans , Male , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Pandemics , Coronavirus Infections/epidemiology , Community-Acquired Infections/diagnosis , Pneumonia , Prospective Studies , Leukocyte Count , BiomarkersABSTRACT
INTRODUCTION: The main aim of this study was to assess the utility of differential white cell count and cell population data (CPD) for the detection of COVID-19 in patients admitted for community-acquired pneumonia (CAP) of different etiologies. METHODS: This was a multicenter, observational, prospective study of adults aged ≥18 years admitted to three teaching hospitals in Spain from November 2019 to November 2021 with a diagnosis of CAP. At baseline, a Sysmex XN-20 analyzer was used to obtain detailed information related to the activation status and functional activity of white cells. RESULTS: The sample was split into derivation and validation cohorts of 1065 and 717 patients, respectively. In the derivation cohort, COVID-19 was confirmed in 791 patients and ruled out in 274 patients, with mean ages of 62.13 (14.37) and 65.42 (16.62) years, respectively (p<0.001). There were significant differences in all CPD parameters except MO-Y. The multivariate prediction model showed that lower NE-X, NE-WY, LY-Z, LY-WY, MO-WX, MO-WY, and MO-Z values and neutrophil-to-lymphocyte ratio were related to COVID-19 etiology with an AUC of 0.819 (0.790, 0.846). No significant differences were found comparing this model to another including biomarkers (p=0.18). CONCLUSIONS: Abnormalities in white blood cell morphology based on a few cell population data values as well as NLR were able to accurately identify COVID-19 etiology. Moreover, systemic inflammation biomarkers currently used were unable to improve the predictive ability. We conclude that new peripheral blood biomarkers can help determine the etiology of CAP fast and inexpensively.
Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia , Adult , Humans , Adolescent , COVID-19/diagnosis , Prospective Studies , Leukocyte Count , Community-Acquired Infections/diagnosis , Pneumonia/diagnosis , BiomarkersABSTRACT
Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated. First, we assessed IGF1R genomic alterations and expression in NSCLC patient tissue samples, as well as IGF1R serum levels. Next, we performed tumor heterotopic transplantation and pulmonary metastases in IGF1R-deficient mice using melanoma and Lewis lung carcinoma (LLC) cells. Herein we report increased amplification and mRNA expression, as well as increased protein expression (IGF1R/p-IGF1R) and IGF1R levels in tumor samples and serum from NSCLC patients, respectively. Moreover, IGF1R deficiency in mice reduced tumor growth, proliferation, inflammation and vascularization, and increased apoptosis after tumor heterotopic transplantation. Following induction of lung metastasis, IGF1R-deficient lungs also demonstrated a reduced tumor burden, and decreased expression of tumor progression markers, p-IGF1R and p-ERK1/2. Additionally, IGF1R-deficient lungs showed increased apoptosis and diminished proliferation, vascularization, EMT and fibrosis, along with attenuated inflammation and immunosuppression. Accordingly, IGF1R deficiency decreased expression of p-IGF1R in blood vessels, fibroblasts, tumor-associated macrophages and FOXP3+ tumor-infiltrating lymphocytes. Our results demonstrate that IGF1R promotes metastatic tumor initiation and progression in lung TME. Furthermore, our research indicates that IGF1R could be a potential biomarker for early prediction of drug response and clinical evolution in NSCLC patients.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Receptor, IGF Type 1 , Animals , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation , Humans , Inflammation , Lung Neoplasms/pathology , Mice , Receptor, IGF Type 1/genetics , Receptor, IGF Type 1/metabolism , Tumor MicroenvironmentABSTRACT
Hemoglobin III (HbIII) is one of the two oxygen reactive hemoproteins present in the bivalve, Lucina pectinata. The clam inhabits a sulfur-rich environment and HbIII is the only hemoprotein present in the system which does not yet have a structure described elsewhere. It is known that HbIII exists as a heterodimer with hemoglobin II (HbII) to generate the stable Oxy(HbII-HbIII) complex but it remains unknown if HbIII can form a homodimeric species. Here, a new chromatographic methodology to separate OxyHbIII from the HbII-HbIII dimer has been developed, employing a fast performance liquid chromatography and ionic exchange chromatography column. The nature of OxyHbIII in solution at concentrations from 1.6 mg/mL to 20.4 mg/mL was studied using small angle X-ray scattering (SAXS). The results show that at all concentrations, the Oxy(HbIII-HbIII) dimer dominates in solution. However, as the concentration increases to nonphysiological values, 20.4 mg/mL, HbIII forms a 30% tetrameric fraction. Thus, there is a direct relationship between the Oxy(HbIII-HbIII) oligomeric form and hemoglobin concentration. We suggest it is likely that the OxyHbIII dimer contributes to active oxygen transport in tissues of L pectinata, where the Oxy(HbII-HbIII) complex is not present.
Subject(s)
Bivalvia/metabolism , Oxyhemoglobins/chemistry , Protein Multimerization , Scattering, Small Angle , X-Ray Diffraction/methods , Amino Acid Sequence , Animals , Bivalvia/genetics , Crystallography, X-Ray , Electrophoresis, Polyacrylamide Gel , Heme/chemistry , Heme/metabolism , Hydrogen Sulfide/metabolism , Oxyhemoglobins/genetics , Oxyhemoglobins/metabolism , Protein Conformation , Sequence Homology, Amino Acid , Tandem Mass Spectrometry/methodsABSTRACT
BACKGROUND: Bendopnea is a symptom described in heart failure (HF) that is related to short-term prognosis; however, its frequency and characteristics in respiratory diseases such as OSAS is still unknown. This study was carried out to evaluate the prevalence of bendopnea in patients with severe obstructive sleep apnea syndrome (OSAS) METHODS: We conducted a study of 95 patients attending a sleep disorders unit with severe OSAS. Bendopnea was considered when shortness of breath occurred within 30s of bending forward. RESULTS: Bendopnea was present in 33/95 of the patients included (34.7%). The median age was 62 years (52-71), 65 were men (68.4%), with a median weight of 92 (81-107) and BMI of 34kg/m2 (±7.1). The median duration of shortness of breath was 5s (2-10). The presence of bendopnea was related to age (p<.0001), obesity (p .004), respiratory diseases (p .01) and HF (p .03). Admission rate was higher in those with bendopnea without reaching statistical significance. CONCLUSION: One-third of patients with severe OSAS present bendopnea. This symptom is related to a higher prevalence of comorbidities (HF, obesity and other respiratory diseases). It is also related to a higher CT90.
Subject(s)
Heart Failure , Sleep Apnea, Obstructive , Comorbidity , Dyspnea/epidemiology , Dyspnea/etiology , Heart Failure/complications , Heart Failure/epidemiology , Humans , Male , Middle Aged , Prognosis , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiologyABSTRACT
Asthma is a chronic inflammatory disease characterized by bronchial hyperresponsiveness, mucus overproduction and airway remodeling. Notably, we have recently demonstrated that insulin-like growth factor 1 receptor (IGF1R) deficiency in mice attenuates airway hyperresponsiveness and mucus secretion after chronic house dust mite (HDM) exposure. On this basis, inbred C57BL/6 and Igf1r-deficient mice were given HDM extract to study the acute inflammatory profile and implication of Igf1r in acute asthma pathobiology. Additionally, Igf1r-deficiency was therapeutically induced in mice to evaluate the resolution of HDM-induced inflammation. Acute HDM exposure in inbred C57BL/6 mice led to a progressive increase in inflammation, airway remodeling and associated molecular indicators. Preventively-induced Igf1r-deficiency showed reduced neutrophil and eosinophil numbers in BALF and bone marrow, a significant reduction of airway remodeling and decreased levels of related markers. In addition, therapeutic targeting of Igf1r promoted the resolution of HDM-induced-inflammation. Our results demonstrate for the first time that Igf1r is important in acute asthma pathobiology and resolution of HDM-induced inflammation. Thus, IGF1R is suggested to be a promising candidate for future therapeutic approaches for the treatment and prevention of asthma.
Subject(s)
Asthma/therapy , Disease Models, Animal , Gene Targeting , Inflammation/therapy , Receptor, IGF Type 1/genetics , Acute Disease , Animals , Bone Marrow Cells , Bronchoalveolar Lavage Fluid , Mice , Mice, Inbred C57BLABSTRACT
IGF1R (Insulin-like Growth Factor 1 Receptor) is a tyrosine kinase with pleiotropic cellular functions. IGF activity maintains human lung homeostasis and is implicated in pulmonary diseases such as cancer, ARDS, COPD, asthma and fibrosis. Here we report that lung transcriptome analysis in mice with a postnatally-induced Igf1r gene deletion showed differentially expressed genes with potentially protective roles related to epigenetics, redox and oxidative stress. After bleomycin-induced lung injury, IGF1R-deficient mice demonstrated improved survival within a week. Three days post injury, IGF1R-deficient lungs displayed changes in expression of IGF system-related genes and reduced vascular fragility and permeability. Mutant lungs presented reduced inflamed area, down-regulation of pro-inflammatory markers and up-regulation of resolution indicators. Decreased inflammatory cell presence in BALF was reflected in diminished lung infiltration mainly affecting neutrophils, also corroborated by reduced neutrophil numbers in bone marrow, as well as reduced lymphocyte and alveolar macrophage counts. Additionally, increased SFTPC expression together with hindered HIF1A expression and augmented levels of Gpx8 indicate that IGF1R deficiency protects against alveolar damage. These findings identify IGF1R as an important player in murine acute lung inflammation, suggesting that targeting IGF1R may counteract the inflammatory component of many lung diseases.
Subject(s)
Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Bleomycin/adverse effects , Inflammation/etiology , Inflammation/metabolism , Receptor, IGF Type 1/deficiency , Acute Lung Injury/pathology , Animals , Biomarkers , Capillary Permeability , Cell Proliferation , Disease Models, Animal , Gene Expression , Gene Expression Profiling , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Inflammation/pathology , Mice , Mice, Knockout , Mice, Transgenic , MutationABSTRACT
A pesar de los múltiples avances diagnósticos o terapéuticos de la medicina de los últimos años, el derrame pleural (DP) continúa siendo una de las enfermedades que con frecuencia tiene que abordar el especialista de aparato respiratorio o el cirujano torácico. El presente texto no tiene como objetivo realizar una revisión exhaustiva sobre las enfermedades que pueden producir DP, su diagnóstico o su tratamiento, sino constituir una actualización de los conocimientos publicados en los últimos años. Teniendo en cuenta la vocación eminentemente práctica de esta normativa, se ha concedido más extensión a las enfermedades que presentan una mayor incidencia o prevalencia, aunque no hemos renunciado a un ligero recordatorio de otras menos frecuentes. Entre los mayores avances destacan los conocimientos sobre la utilidad de la ecografía torácica, los fibrinolíticos y los agentes pleurodésicos, o la utilización de nuevas técnicas de drenaje pleural, como los tubos torácicos finos o los catéteres tunelizados. La actualización periódica de las normativas favorece la potencial incorporación de nuevas técnicas en el estudio de la enfermedad pleural
Although during the last few years there have been several important changes in the diagnostic or therapeutic methods, pleural effusion is still one of the diseases that the respiratory specialist have to evaluate frequently. The aim of this paper is to update the knowledge about pleural effusions, rather than to review the causes of pleural diseases exhaustively. These recommendations have a longer extension for the subjects with a direct clinical usefulness, but a slight update of other pleural diseases has been also included. Among the main scientific advantages are included the thoracic ultrasonography, the intrapleural fibrinolytics, the pleurodesis agents, or the new pleural drainages techniques
Subject(s)
Humans , Pleural Effusion/diagnosis , Pleural Effusion/therapy , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/therapy , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/therapy , Hemothorax/diagnosis , Hemothorax/therapyABSTRACT
Although during the last few years there have been several important changes in the diagnostic or therapeutic methods, pleural effusion is still one of the diseases that the respiratory specialist have to evaluate frequently. The aim of this paper is to update the knowledge about pleural effusions, rather than to review the causes of pleural diseases exhaustively. These recommendations have a longer extension for the subjects with a direct clinical usefulness, but a slight update of other pleural diseases has been also included. Among the main scientific advantages are included the thoracic ultrasonography, the intrapleural fibrinolytics, the pleurodesis agents, or the new pleural drainages techniques.
Subject(s)
Pleural Effusion/diagnosis , Pleural Effusion/therapy , Algorithms , Combined Modality Therapy , Diagnostic Imaging/methods , Exudates and Transudates/chemistry , Humans , Nutritional Support , Pleural Effusion/etiology , Pleural Effusion/microbiology , Pleural Effusion, Malignant/diagnosis , Pleural Effusion, Malignant/therapy , Pleurodesis/methods , Pneumonia/complications , Pneumonia/drug therapy , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Sclerosing Solutions/therapeutic use , Sensitivity and Specificity , Tuberculosis, Pleural/complications , Tuberculosis, Pleural/diagnosis , Tuberculosis, Pleural/drug therapyABSTRACT
Lucina pectinata haemoglobin II (HbII) transports oxygen in the presence of H(2)S to the symbiotic system in this bivalve mollusc. The composition of the haem pocket at the distal site includes TyrB10 and GlnE7, which are very common in other haem proteins. Obtaining crystals of oxyHbII at various pH values is required in order to elucidate the changes in the conformations of TyrB10 and GlnE7 and structural scenarios induced by changes in pH. Here, the growth of crystals of oxyHbII using the capillary counterdiffusion (CCD) technique at various pH values using a two-step protocol is reported. In the first step, a mini-screen was used to validate sodium formate as the best precipitating reagent for the growth of oxyHbII crystals. The second step, a pH screen typically used for optimization, was used to produce crystals in the pH range 4-9. Very well faceted prismatic ruby-red crystals were obtained at all pH values. X-ray data sets were acquired using synchrotron radiation of wavelength 0.886 A (for the crystals obtained at pH 5) and 0.908 A (for those obtained at pH 4, 8 and 9) to maximum resolutions of 3.30, 1.95, 1.85 and 2.00 A for the crystals obtained at pH 4, 5, 8 and 9, respectively. All of the crystals were isomorphous and belonged to space group P4(2)2(1)2.
Subject(s)
Bivalvia/chemistry , Hemoglobins/chemistry , Animals , Crystallization , Hydrogen-Ion Concentration , X-Ray DiffractionABSTRACT
The native oxygen-carrier haemoglobins complex (HbII-III) is composed of haemoglobin II (HbII) and haemoglobin III (HbIII), which are found in the ctenidia tissue of the bivalve mollusc Lucina pectinata. This protein complex was isolated and purified from its natural source and crystallized using the vapour-diffusion and capillary counter-diffusion methods. Oxy and cyano derivatives of the complex crystallized using several conditions, but the best crystals in terms of quality and size were obtained from sodium formate pH 5 using the counter-diffusion method in a single capillary. Crystals of the oxy and cyano complexes, which showed a ruby-red colour and nonsingular prismatic shapes, scattered X-rays to resolution limits of 2.15 and 2.20 A, respectively, using a 0.886 A synchrotron-radiation source. The crystals belonged to the tetragonal system, space group P4(2)2(1)2, with unit-cell parameters a = b = 74.07, c = 152.07 and a = b = 73.83, c = 152.49 A for the oxy and cyano complexes, respectively. The asymmetric unit of both crystals is composed of a single copy of the heterodimer, with Matthew coefficients (V(M)) of 3.08 and 3.06 A(3) Da(-1) for the oxy and cyano complexes, respectively, which correspond to a solvent content of approximately 60.0% by volume.
