COVID-19: A Comprehensive Review on Cardiovascular Alterations, Immunity, and Therapeutics in Older Adults.

Here, we present a review focusing on three relevant issues related to COVID-19 and its impact in older adults (60 years and older). SARS-CoV-2 infection starts in the respiratory system, but the development of systemic diseases accompanied by severe clinical manifestations has also been reported, with cardiovascular and immune system dysfunction being the major ones. Additionally, the presence of comorbidities and aging represent major risk factors for the severity and poor prognosis of the disease. Since aging-associated decline has been largely related to immune and cardiovascular alterations, we sought to investigate the consequences and the underlying mechanisms of these pathologies to understand the severity of the illness in this population. Understanding the effects of COVID-19 on both systems should translate into comprehensive and improved medical care for elderly COVID-19 patients, preventing cardiovascular as well as immunological alterations in this population. Approved therapies that contribute to the improvement of symptoms and a reduction in mortality, as well as new therapies in development, constitute an approach to managing these disorders. Among them, we describe antivirals, cytokine antagonists, cytokine signaling pathway inhibitors, and vaccines.

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission.

BCR-ABL is an aberrant tyrosine kinase responsible for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs) induce a potent antileukemic response mostly based on the inhibition of BCR-ABL, but they also increase the activity of Natural Killer (NK) and CD8+ T cells. After several years, patients may interrupt treatment due to sustained, deep molecular response. By unknown reasons, half of the patients relapse during treatment interruption, whereas others maintain a potent control of the residual leukemic cells for several years. In this study, several immunological parameters related to sustained antileukemic control were analyzed. According to our results, the features more related to poor antileukemic control were as follows: low levels of cytotoxic cells such as NK, (Natural Killer T) NKT and CD8±TCRγß+ T cells; low expression of activating receptors on the surface of NK and NKT cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX. A Random Forest algorithm predicted 90% of the accuracy for the classification of CML patients in groups of relapse or non-relapse according to these parameters. Consequently, these features may be useful as biomarkers predictive of CML relapse in patients that are candidates to initiate treatment discontinuation.

Src Tyrosine Kinase Inhibitors: New Perspectives on Their Immune, Antiviral, and Senotherapeutic Potential.

Deregulated activity of the Src tyrosine kinases leads to malignant transformation. Since the FDA approval of the tyrosine kinase inhibitor, imatinib, in 2001 for the treatment of chronic myeloid leukemia (CML), the number of these inhibitors together with Src tyrosine kinase inhibitors (STKIs) has increased notably due to their beneficial effects. Dasatinib, a second-generation STKI inhibitor widely studied, proved high efficiency in CML patients resistant to imatinib. In the last decade STKIs have also been implicated and showed therapeutic potential for the treatment of diverse pathologies other than cancer. In this regard, we review the properties of STKIs, dasatinib in particular, including its immunomodulatory role. Similarly, the potential benefits, adverse effects, and safety concerns of these inhibitors regarding viral infections are considered. Moreover, since life expectancy has increased in the last decades accompanied by age-related morbidity, the reduction of undesirable effects associated to aging has become a powerful therapeutic target. Here, we comment on the ability of STKIs to alleviate age-associated physical dysfunction and their potential impact in the clinic.

CD26 and Asthma: a Comprehensive Review.

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.

Effects on soil phosphorus dynamics of municipal solid waste compost addition to a burnt and unburnt forest soil.

The main aim of this research was to assess the effects of municipal solid waste compost (MSWC) addition to a burnt and unburnt calcareous soil, on the distribution of soil P forms in particle-size and extractable fractions. Three MSWC doses (1, 2 and 4% w/w) were added to burnt and unburnt soil samples and were incubated for 92 days at 29 °C and 75% of field capacity moisture. A particle-size fractionation followed by a sequential P extraction procedure was carried out. The burnt soil showed significantly lower concentrations of organic P forms (Porg) and significantly higher concentrations of stable P forms than the unburnt soil. Besides, in both burnt and unburnt soils, most P-forms presented higher concentrations in the clay fractions than in the sand and silt fractions, possibly due to the different proportions of microbial synthesized and plant-derived substances in the different particle-size fractions. Finer fractions of MSWC showed higher total P and Porg concentrations than coarser fractions. Our results showed that the highest dose of MSWC` was the most effective one for the rehabilitation of the burnt soil. MSWC amendment also caused an increase in soil P availability in the unburnt soil which initially contained relatively low levels of P. During the incubation process, a high proportion of organic P contained in the MSWC was mineralized into inorganic P forms. These forms were precipitated with Ca cations which are very abundant in these calcareous soils, significantly increasing the P fraction extracted by HCl in both amended soils. Hence, adding compost to the soil involved an increase in the available P reservoir in the long term. The combination of particle-size fractionation, chemical sequential extraction and incubation experiments can be a valuable tool for splitting soil phosphorus into different fractions regarding their availability in relation to short and long-term transformations in soil.

Análisis del líquido y elastancia pleurales como predictores de respuesta a la pleurodesis en los derrames pleurales malignos / Pleural Fluid Analysis and Pleural Elastance as Predictors of Response to Pleurodesis in Patients With Malignant Pleural Effusion

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Síndrome de Sjögren primario con derrame pleural / Primary Sjögren Syndrome With Pleural Effusion

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Urinothorax: a systematic review.

BACKGROUND: The characteristics of patients with urinothorax (UT) are poorly defined. METHODS: A systematic review was performed searching for studies reporting clinical findings, pleural fluid (PF) characteristics, and the most effective treatment of UT. Case descriptions and retrospective studies were included. RESULTS: The review included 78 studies with a total of 88 patients. Median age was 45 years, male/female ratio was 1.6:1 and in 76% of cases the etiology was trauma. Pleural effusion (PE) was predominantly unilateral (87%) and occupied over 2/3 of the hemithorax in most cases (64.4%). PF was straw-colored (72.7%) or hematic (27.3%) with urine-like odor in all cases. PF was transudate in 56.2% of cases (18/32) and among 14 exudates (43.8%), 3 were concordant exudates, 1 protein-discordant and 10 LDH-discordant, with lymphocyte (44.4%) and neutrophil (38.5%) predominance. The PF/serum (PF/S) creatinine ratio was >1 in all cases except one (97.9%). The diagnosis was established on the basis of PF/S creatinine ratio >1 (56.6%), urinary tract contrast extravasation (12%), abnormal computed tomography (8.4%), laparotomy findings (6%), and association of obstructive uropathy with PE (6%). The outcome was favorable (74/77; 96.1%) when treatment was direct towards the uropathy (alone or associated with thoracentesis/thoracic drainage). Outcome was unfavorable in the 15 patients who were only treated with thoracentesis/thoracic drainage. CONCLUSIONS: UT is usually traumatic, unilateral, and PF does not have a specific pattern or cellularity predominance, with a PF/S creatinine ratio almost always >1. Treatment should include the uropathy, with or without PF evacuation.

Asthma exacerbations: factors related to longer hospital stay.

BACKGROUND: Hospital admissions account for a significant part of asthma cost, but with significant differences between geographic areas. AIMS: The aim of our study is to analyse hospital admissions due to asthma, as well as the factors associated with longer hospital stays. METHODS: A review was retrospectively carried out on all admissions of patients over 18 years old due to exacerbation of asthma occurring in our hospital between the years 2000 and 2010. The personal characteristics of each patient, the asthma personal history, characteristics of every exacerbation, as well as the treatment before admission and after hospital discharge were recorded. RESULTS: During the study period, there were 2163 hospital admissions in 1316 patients (mean age 62.6 years; mean hospital stay 11.6 days). The admissions mainly occur in winter, in the 56-75-year age group, and in patients with severe asthma. Female sex, higher comorbidity, a greater number of emergencies due to asthma in the previous year, and baseline treatment with theophylline were independently associated to longer hospital stay. CONCLUSIONS: The management of asthma in our population seems improvable. There appears to be a need to optimise both the diagnosis and treatment of the disease, and to identify risk factors as important as tobacco habits. As regards exacerbations, the hospital stay and mortality must be significantly reduced.

Predictive models of malignant transudative pleural effusions.

BACKGROUND: There are no firm recommendations when cytology should be performed in pleural transudates, since some malignant pleural effusions (MPEs) behave biochemically as transudates. The objective was to assess when would be justified to perform cytology on pleural transudates. METHODS: Consecutive patients with transudative pleural effusion (PE) were enrolled and divided in two groups: malignant and non-MPE. Logistic regression analysis was used to estimate the probability of malignancy. Two prognostic models were considered: (I) clinical-radiological variables; and (II) combination of clinical-radiological and analytical variables. Calibration and discrimination [receiver operating characteristics (ROC) curves and area under the curve (AUC)] were performed. RESULTS: A total of 281 pleural transudates were included: 26 malignant and 255 non-malignant. The AUC obtained with Model 1 (left PE, radiological images compatible with malignancy, absence of dyspnea, and serosanguinous appearance of the fluid), and Model 2 (the variables of Model 1 plus CEA) were 0.973 and 0.995, respectively. Although no false negatives are found in Models 1 and 2 to probabilities of 11% and 14%, respectively, by applying bootstrapping techniques to not find false negatives in 95% of other possible samples would require lowering the cut-off points for the aforementioned probabilities to 3% (Model 1) and 4% (Model 2), respectively. The false positive results are 32 (Model 1) and 18 (Model 2), with no false negatives. CONCLUSIONS: The applied models have a high discriminative ability to predict when a transudative PE may be of neoplastic origin, being superior to adding an analytical variable to the clinic-radiological variables.

Spontaneous bilateral haemothorax as presentation of primary pleural epithelioid haemangioendothelioma.

Pleural epithelioid haemangioendothelioma (EHE) is a rare tumour that originates in the vascular endothelium with an intermediate degree of malignancy between haemangioma and angiosarcoma. Smoking and asbestos exposure are unproven risk factors and diagnosis is usually confirmed by thoracoscopy, since pleural fluid (PF) cytology is often not conclusive. Immunohistochemistry can also help to confirm the diagnosis. We report an 85-year-old patient with bilateral pleural EHE diagnosed by thoracoscopy, who debuted with a spontaneous bilateral haemothorax, the second described so far, and we conducted a thorough review of the literature to describe the clinical, radiological and prognostic features, as well as the PF, of this rare tumour.

Dasatinib-induced pleural effusion: Chylothorax, an option to consider.

Dasatinib is a drug for treatment of oncogene fusion protein BCR-ABL-positive chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant/intolerant to imatinib. Pleural effusion (PE) is a common adverse effect, and in this context, we present four cases seen due to this cause. One of them is a chylothorax. The PE grade is variable, and the physiopathology is not well established, although a block in T-lymphocyte function or inhibition of platelet-derived growth factor receptor-ß is suggested being involved. The PE is generally a lymphocyte-predominant exudate, but can also present as chylothorax. Several factors have been associated with its appearance, particularly the administration in two daily doses. Low grade (1-2) PEs usually respond well to interrupt the treatment while those of higher grade may also require therapeutic thoracentesis and corticosteroids. There are currently no firm guidelines that establish when to resort to one form of treatment or another.

Characteristics of patients with pseudochylothorax-a systematic review.

BACKGROUND: Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory disorders. Nevertheless, the characteristics of patients with PCT are poorly defined. METHODS: A systematic review was performed across two electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of PCT. Case descriptions and retrospective studies were included. RESULTS: The review consisted of 62 studies with a total of 104 patients. Median age was 58 years, the male/female ratio was 2.6/1, and in the 88.5% of cases the etiology was tuberculosis (TB) or rheumatoid arthritis (RA). PE was usually unilateral (88%) and occupied greater than one-third of the hemithorax (96.3%). There was no evidence of pleural thickening in 20.6% of patients, and 14 patients had a previous PE. The pleural fluid (PF) was an exudate, usually milky (94%) and with a predominance of lymphocytes (61.1%). The most sensitive tests to establish the diagnosis were the cholesterol/triglycerides ratio (CHOL/TG ratio) >1, and the presence of cholesterol crystals (97.4% and 89.7%, respectively). PF culture for TB was positive in the 34.1% of patients. Favorable outcomes with medical treatment, therapeutic thoracentesis, decortication/pleurectomy, pleurodesis, thoracic drainage and thoracoscopic drainage were achieved in 78.9%, 47.8%, 86.7%, 66.6%, 37.5% and 42.9%, respectively. CONCLUSIONS: PCT is usually tuberculous or rheumatoid, unilateral and the PF is a milky exudate. The presence of cholesterol crystals and a CHOL/TG ratio >1 are the most sensitive test for the diagnosis. The lack of pleural thickening does not rule out PCT. Treatment should be sequential, treating the underlying causes, and assessing the need for interventional techniques.

Characteristics of Patients with Lymphangioleiomyomatosis and Pleural Effusion: A Systematic Review.

The characteristics of patients with lymphangioleiomyomatosis (LAM) are poorly defined, as they may present with or without pleural effusion (PE). We performed a systematic review across four electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of LAM. Case descriptions and retrospective studies were included, unrestricted by year of publication. The review consisted of 94 studies (199 patients) spanning a period of nearly 55 years. The median age was 38 years (range: 1 month to 69 years), and 79.7% were between 21 and 50 years old. All cases had dyspnea, 95% had a cough, and 87.5% had chest pain. PE was exudative chylothorax, usually unilateral (76%) and right-sided, predominantly lymphocytic, and with proportionately higher levels of proteins than lactate dehydrogenase. Sirolimus was effective in all cases, completely in 87%, and partially in 13%, although the number of patients receiving sirolimus was small. The present study confirmed that LAM and PE mainly occur in women of childbearing age (third to fifth decade of life). PE was usually unilateral and presented as a lymphocyte-predominant chylous exudate. The most effective treatment for PE seems to be sirolimus, although studies with larger series are needed to confirm this.

Predicting malignant and tuberculous pleural effusions through demographics and pleural fluid analysis of patients.

INTRODUCTION: The differential diagnosis of malignant and tuberculous pleural effusion is frequently difficult. OBJECTIVES: The aim of our study is to determine the discrimination value of demographic parameters and different biological markers in pleural fluid. METHODS: In pleural fluid obtained from 106 patients with tuberculous, 250 with malignant and 218 with miscellaneous pleural effusion, clinical and analytical parameters were analysed, applying polytomous regression analysis and the receiver operating characteristic (ROC) curves. RESULTS: The three groups could be differentiated using the measured markers. Age, tumour necrosing factor-alpha, lactate dehydrogenase (LDH), adenosine deaminase (ADA), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were significant predictors for discriminating tuberculous from malignant pleural effusions; nucleated cells, lymphocytes, cholesterol, LDH, ADA, CRP, CEA and CA15.3 distinguish between malignant and miscellaneous pleural effusions. The ROC areas (95% confidence interval) were, 0.973 (0.953, 0.992) for tuberculous, 0.922 (0.900, 0.943) for miscellaneous, and 0.927 (0.907, 0.948) for malignant pleural effusion. The polytomous model correctly classified a significantly high proportion of patients with tuberculosis (85.8%) and cancer (81.6%). The incorrect classification rate was 17.8%, which increased to 19.5% in the correction using bootstrap. CONCLUSIONS: The results obtained to estimate the probability of tuberculous and malignant pleural effusion confirm that this model achieves a high diagnostic accuracy. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures.

Derrame pleural y sarcoidosis: una asociación poco frecuente / Pleural Effusion and Sarcoidosis: An Unusual Combination

La afectación pleural en la sarcoidosis es baja y se puede manifestar de diversas formas. Con el objetivo de documentar la frecuencia y las características del derrame pleural en los pacientes con sarcoidosis, revisamos los casos diagnosticados en nuestro centro entre enero de 2001 y diciembre de 2012. De los 195 pacientes con sarcoidosis identificados, 3 (2 hombres y una mujer) tenían un derrame pleural unilateral (1,5%): uno derecho y 2 izquierdo; 2 en estadio ii y uno en estadio iv. El derrame de los 2 que se puncionaron era un exudado de predominio linfocítico. Uno de ellos correspondía a un quilotórax y el otro presentaba valores elevados de CA-125. Estos derrames suelen ser exudados serosos (a veces quilotórax), paucicelulares, de predominio linfocítico, con unas proteínas proporcionalmente más elevadas que la LDH. Pueden evolucionar favorablemente de forma espontánea, si bien en la mayoría de los casos se tratan con corticoides (AU)

Pleural involvement in sarcoidosis is uncommon and appears in several forms. To document the incidence and characteristics of pleural effusion in sarcoidosis patients, a review of the cases diagnosed in our centre between January 2001 and December 2012 was carried out. One hundred and ninety-five patients with sarcoidosis were identified; three (two men and one woman) presented with unilateral pleural effusion (1.5%): one in the right side and two in the left. Two were in stage ii and one was in stage iv. The pleural fluid of the two patients who underwent thoracocentesis was predominantly lymphocytic. One of these patients presented chylothorax and the other had high CA-125 levels. In general, these effusions are lymphocyte-rich, paucicellular, serous exudates (sometimes chylothorax) and contain proportionally higher levels of protein than LDH. Most cases are treated with corticosteroids, although it may resolve spontaneously (AU)

Derrame pleural tuberculoso / Tuberculous Pleural Effusion

El derrame pleural tuberculoso (DPTB) es la causa más frecuente de tuberculosis (TB) extrapulmonar en nuestro país y uno de los motivos más habituales de derrame pleural. Si bien la incidencia disminuye progresivamente (4,8 casos/100.000 habitantes en el año 2009), el porcentaje de DPTB se mantiene estable con respecto al número de casos totales de TB (14,3-19,3%). Casi las dos terceras partes son hombres, más del 60% tienen edades entre los 15-44 años y es más frecuente en los pacientes infectados por el virus de la inmunodeficiencia humana. La patogenia suele ser una reacción de hipersensibilidad retardada. La clínica varía dependiendo de la población (más aguda en los jóvenes y más prolongada en los ancianos). El derrame es casi invariablemente un exudado unilateral (según los criterios de Light), más frecuentemente del lado derecho, y la prueba de la tuberculina es negativa en la tercera parte de los casos. Los diagnósticos de certeza tienen limitaciones, por lo que para ello se han utilizado diversos biomarcadores en el líquido pleural. La asociación de la adenosina desaminasa y del porcentaje de linfocitos puede ser útil para el diagnóstico. El tratamiento es el de cualquier TB. No parece recomendable añadir corticoides y el drenaje torácico podría contribuir, en los grandes derrames, a una mejoría más rápida de los síntomas

Tuberculous pleural effusion (TBPE) is the most common form of extrapulmonary tuberculosis (TB) in Spain, and is one of the most frequent causes of pleural effusion. Although the incidence has steadily declined (4.8 cases/100 000 population in 2009), the percentage of TBPE remains steady with respect to the total number of TB cases (14.3%-19.3%). Almost two thirds are men, more than 60% are aged between 15 and 44 years, and it is more common in patients with human immunodeficiency virus. The pathogenesis is usually a delayed hypersensitivity reaction. Symptoms vary depending on the population (more acute in young people and more prolonged in the elderly). The effusion is almost invariably a unilateral exudate (according to Light's criteria), more often on the right side, and the tuberculin test is negative in one third of cases. There are limitations in making a definitive diagnosis, so various pleural fluid biomarkers have been used for this. The combination of adenosine deaminase and lymphocyte percentage may be useful in this respect. Treatment is the same as for any TB. The addition of corticosteroids is not advisable, and chest drainage could help to improve symptoms more rapidly in large effusions