Cytotoxic Natural Killer Subpopulations as a Prognostic Factor of Malignant Pleural Effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a sign of advanced disease of poor prognosis. As natural killer (NK) cells are involved in the first line of tumour defence, we aimed to validate a new diagnostic and prognostic indicator for MPE based on NK subpopulations of pleural fluid (PF) and peripheral blood (PB). METHODS: NK subpopulations were determined in PF and PB in 71 patients with malignant, paramalignant or benign pleural effusion. The receiver operating characteristic (ROC) curves, Kaplan-Meier, multivariable Cox model and decision trees created with the CHAID (Chi-square automatic interaction detector) methodology were employed. RESULTS: We demonstrated that the PF/PB ratios of the CD56 bright CD16- and CD56 dim CD16- NK subpopulations were higher (p = 0.013 and p = 0.003, respectively) in MPEs and paramalignant pleural effusions (PPEs) than in benign ones, with an AUC of 0.757 and 0.741, respectively. The PF/PB ratio of CD16+ NK and CD57+ NK obtained a higher hazard ratio (HR) in the crude Cox's regression analysis. In the adjusted Cox's regression analysis, the PF/PB ratio of CD16+ NK gave the highest HR (HR 6.1 [1.76-21.1]) (p = 0.004). In the decision tree created for the MPE prognosis, we observed that the main predictor variable among the studied clinical, radiological, and analytical variables was lung mass, and that 92.9% of the patients who survived had a PF/PB ratio of the CD56 dim CD16+ NK subpopulation ≤ 0.43. CONCLUSIONS: Our data suggest that both the PF/PB ratios of cytotoxic subpopulations CD57+ NK and CD16+ NK are useful as a prognostic factor of MPE. Other subpopulations (CD56 bright CD16- and CD56 dim CD16- NK) could help to diagnose MPE.

Predicting Malignant and Paramalignant Pleural Effusions by Combining Clinical, Radiological and Pleural Fluid Analytical Parameters.

BACKGROUND: The usefulness of clinical, radiological and pleural fluid analytical parameters for diagnosing malignant and paramalignant pleural effusion is not clearly stated. Hence this study aimed to identify possible predictor variables of diagnosing malignancy in pleural effusion of unknown aetiology. METHODS: Clinical, radiological and pleural fluid analytical parameters were obtained from consecutive patients who had suffered pleural effusion of unknown aetiology. They were classified into three groups according to their final diagnosis: malignant, paramalignant and benign pleural effusion. The CHAID (Chi-square automatic interaction detector) methodology was used to estimate the implication of the clinical, radiological and analytical variables in daily practice through decision trees. RESULTS: Of 71 patients, malignant (n = 31), paramalignant (n = 15) and benign (n = 25), smoking habit, dyspnoea, weight loss, radiological characteristics (mass, node, adenopathies and pleural thickening) and pleural fluid analytical parameters (pH and glucose) distinguished malignant and paramalignant pleural effusions (all with a p < 0.05). Decision tree 1 classified 77.8% of malignant and paramalignant pleural effusions in step 2. Decision tree 2 classified 83.3% of malignant pleural effusions in step 2, 73.3% of paramalignant pleural effusions and 91.7% of benign ones. CONCLUSIONS: The data herein suggest that the identified predictor values applied to tree diagrams, which required no extraordinary measures, have a higher rate of correct identification of malignant, paramalignant and benign effusions when compared to techniques available today and proved most useful for usual clinical practice. Future studies are still needed to further improve the classification of patients.

[Influence of Clinical Practice Guidelines on the Diagnosis and Treatment of Idiopathic Pulmonary Fibrosis. Data from the Registry of the Spanish Society of Pulmonology and Thoracic Surgery]. / Influencia de las guías de práctica clínica en el diagnóstico y tratamiento de la fibrosis pulmonar idiopática. Datos del Registro de la Sociedad Española de Neumología y Cirugía Torácica.

Objective: The objective of the study was to analyze the diagnostic process and the time until the start of treatment of patients with idiopathic pulmonary fibrosis in relation to the publication of successive clinical practice guide. Material and methods: Multicenter, observational, ambispective study, in which patients includes in the idiopathic pulmonary fibrosis registry of the Spanish Society of Pulmonologist and Thoracic Surgery were analyzed. An electronic data collection notebook was enabled on the society's website. Sociodemographic and clinical variables were collected at diagnosis and follow-up of the patients. Results: From January 2012 to december 2019, 1064 patients were included in the registry, with 929 finally analyzed. The diagnosis process varied depending on the year in which it was performed, and the radiological pattern observed in the high-resolution computed tomography. Up to 26.3% of the cases (244) were diagnosed with chest high-resolution computed tomography and clinical evaluation. Surgical biopsy was used up to 50.2% of cases diagnosed before 2011, while it has been used in 14.2% since 2018. The median time from the onset of symptoms to diagnosis was 360 days (IQR 120-720), taking more than 2 years in the 21.0% of patients. A percentage of 79.4 of patients received antifibrotic treatment. The average time from diagnosis to the antifibrotic treatment has been 309 ± 596.5 days, with a median of 49 (IQR 0-307). Conclusions: The diagnostic process, including the time until diagnosis and the type of test used, has changed from 2011 to 2019, probably due to advances in clinical research and the publication of diagnostic-therapeutic consensus guidelines.

Diagnostic delay of associated interstitial lung disease increases mortality in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main extra-articular organ affected is the lung, sometimes in the form of diffuse interstitial lung disease (ILD) and conditions the prognosis. A multicenter, observational, descriptive and cross-sectional study of consecutive patients diagnosed with RA-ILD. Demographic, analytical, respiratory functional and evolution characteristics were analyzed to evaluate the predictors of progression and mortality. 106 patients were included. The multivariate analysis showed that the diagnostic delay was an independent predictor of mortality (HR 1.11, CI 1.01-1.23, p = 0.035). Also, age (HR 1.33, 95% CI 1.09-1.62, p = 0.0045), DLCO (%) (HR 0.85, 95% CI 0.73-0.98, p = 0.0246), and final SatO2 (%) in the 6MWT (HR 0.62, 95% CI 0.39-0.99, p = 0.0465) were independent predictor variables of mortality, as well as GAP index (HR 4.65, 95% CI 1.59-13.54, p = 0.0051) and CPI index (HR 1.12, 95% CI 1.03-1.22, p = 0.0092). The withdrawal of MTX or LFN after ILD diagnosis was associated with disease progression in the COX analysis (HR 2.18, 95% CI 1.14-4.18, p = 0.019). This is the first study that highlights the diagnostic delay in RA-ILD is associated with an increased mortality just like happens in IPF.

Porcine Breed, Sex, and Production Stage Influence the Levels of Health Status Biomarkers in Saliva Samples.

In this study, the influence of several factors such as breed, sex, and production stage over the normal range values of salivary biomarkers of health status was evaluated in pigs. A total of 409 pigs of 2 different breeds (conventional Large White × Duroc and Iberian pigs) were included in the study. Animals were divided into different groups according to their sex (male or female) and the stage of the production cycle they were in (post-weaning, nursery, fattening, and finishing). The levels of an inflammatory marker, adenosine deaminase (ADA), and two acute phase proteins, C-reactive protein (CRP) and haptoglobin (Hp) were measured in saliva samples. Moreover, the total antioxidant capacity level (TAC) was quantified for the first time in porcine saliva; therefore, an analytical validation and stability analysis during storage at -80°C were also performed. Differences according to breed were observed for all the markers studied; thus, the influence of age and sex on the normal range values were studied separately for conventional and Iberian pigs. In Large White × Duroc pigs the overall median values of ADA, CRP, Hp and TAC were 282 U/L, 10.49 ng/mL, 0.88 µg/mL, and 21.73 µM Trolox equivalents, respectively. However, higher values of inflammatory marker and acute phase proteins were observed in males at the initial stages of the production cycle, while females presented higher values when they had reached sexual maturity. In Iberian pigs the overall median values observed were 585 U/L, 4.81 ng/mL, 0.63 µg/mL, and 21.21 µM Trolox equivalents for ADA, CRP, Hp, and TAC respectively with slight differences in the influence of the studied factors. Sex differences were not observed in the levels of acute phase proteins in Iberian pigs, probably due to the castration of males during the first days of life; however, ADA levels were found to be higher in male pigs at the end of the production cycle. It could be concluded that breed, sex, and production stage influence the range values of salivary markers of health status in pigs and should be taken into account to further establish reference intervals.

Novel association of five HLA alleles with HIV-1 progression in Spanish long-term non progressor patients.

Certain host genetic variants, especially in the human leucocyte antigen (HLA) region, are associated with different progression of HIV-1-induced diseases and AIDS. Long term non progressors (LTNP) represent only the 2% of infected patients but are especially relevant because of their efficient HIV control. In this work we present a global analysis of genetic data in the large national multicenter cohort of Spanish LTNP, which is compared with seronegative individuals and HIV-positive patients. We have analyzed whether several single-nucleotide polymorphisms (SNPs) including in key genes and certain HLA-A and B alleles could be associated with a specific HIV phenotype. A total of 846 individuals, 398 HIV-1-positive patients (213 typical progressors, 55 AIDS patients, and 130 LTNPs) and 448 HIV-negative controls, were genotyped for 15 polymorphisms and HLA-A and B alleles. Significant differences in the allele frequencies among the studied populations identified 16 LTNP-associated genetic factors, 5 of which were defined for the first time as related to LTNP phenotype: the protective effect of HLA-B39, and the detrimental impact of HLA-B18, -A24, -B08 and -A29. The remaining eleven polymorphisms confirmed previous publications, including the protective alleles HLA-B57, rs2395029 (HCP5), HLA bw4 homozygosity, HLA-B52, HLA-B27, CCR2 V64I, rs9264942 (HLA-C) and HLA-A03; and the risk allele HLA bw6 homozygosity. Notably, individual Spanish HIV-negative individuals had an average of 0.12 protective HLA alleles and SNPs, compared with an average of 1.43 protective alleles per LTNP patient, strongly suggesting positive selection of LTNP. Finally, stratification of LTNP according to viral load showed a proportional relationship between the frequency of protective alleles with control of viral load. Interestingly, no differences in the frequency of protection/risk polymorphisms were found between elite controllers and LTNPs maintaining viral loads <2.000 copies/mL throughout the follow-up.

Pediatric Arterial Ischemic Stroke: Clinical Presentation, Risk Factors, and Pediatric NIH Stroke Scale in a Series of Chilean Patients.

Stroke is an important cause of morbidity and mortality in children. Clinical presentation is diverse, and multiple risk factors have been described. The aim of this retrospective study is to describe the clinical presentation, risk factors, and the Pediatric National Institute of Health Stroke Scale (PedNIHSS) in a series of pediatric Chilean patients with the diagnosis of arterial ischemic stroke (AIS). Children diagnosed with AIS aged between 29 d and 18 y were enrolled (1989 to 2016). Clinical characteristics and risk factors were described. PedNIHSS severity score was estimated for patients older than 4 mo of age. Sixty-two patients were included, 66% were male, and the mean age of presentation was 3.5 y. Seventy-nine percent presented motor deficit, 45% seizures, and 15% consciousness impairment. Eighty-two percent had a unilateral stroke and 73% had anterior circulation territory affected. The main risk factors were arteriopathy (63%) and infection (43%). The PedNIHSS mean was 7.6, ranging between 0 and 17. In the categories in which it was possible to apply χ2 test, only the acute systemic conditions category was statistically significant (P = 0.03), being higher in the group of patients younger than 3 y old. We confirmed male predominance in AIS and the most frequent presenting symptom was motor deficit. We found at least 1 risk factor in all patients with complete information. We confirmed arteriopathy as the most frequent risk factor, and acute systemic conditions were higher in patients younger than 3 y old with statistical significance (P = 0.03). The majority of patients presented mild to moderate severity in the PedNIHSS score.

Risk Factors for Perinatal Arterial Ischemic Stroke: A Case-Control Study.

INTRODUCTION: Arterial ischemic stroke in newborns is an important cause of neonatal morbidity and mortality. Its pathophysiology and associated risk factors are not yet clearly understood and defined. OBJECTIVE: The aim of this retrospective study was to investigate possible risk factors in diagnosed cases of PAIS (perinatal arterial ischemic stroke). MATERIALS AND METHODS: Case-control study. Clinical data of patients with PAIS diagnosis were analyzed. Two healthy controls were selected for each PAIS case, matched for gestational age. Risk factors were explored using univariable and multivariable analysis. OUTCOME: 40 patients were included in the study, 24 males and 16 females; 52.5% of cases were diagnosed within the first month of birth, and 47.5% were retrospectively diagnosed. The results showed a male predominance (66.7%). The distribution of cerebral ischemic injury was predominantly medial cerebral artery (87.5%) and occurred more commonly in the left cerebral hemisphere (62.5%). Significant risk factors in the univariate analysis (P < 0.05) were primiparity, stillbirth, neonatal sepsis, asphyxia, twin pregnancy, placenta abruption, emergency cesarean section, Apgar score ≤7 after 5 min, breech presentation, and hyperbilirubinemia. In the multivariate analysis, primiparity (OR 11.74; CI 3.28-42.02), emergency cesarean section (OR 13.79; CI 3.51-54.13), birth asphyxia (OR 40.55; CI 3.08-532.94) and Apgar score ≤7 after 5 min (OR 13.75; CI 1.03-364.03) were significantly associated factors with PAIS. Only five (16.6%) patients had an abnormal thrombophilia study. CONCLUSION: Risk factors of primiparity, emergency cesarean section, birth asphyxia, and Apgar score ≤7 after 5 min were significantly associated with perinatal stroke. More studies with a larger number of patients and with prolonged follow up are required to establish more clearly the associated risk factors involved in this pathology.

Impacto de brote por Covid-19 en las causas de egresos hospitalarios a nivel nacional por enfermedades del sistema nervioso central en población pediátrica durante el primer año de pandemia en Chile / Impact of Covid-19 outbreak in the causes of hospital discharges at national level due to central nervous system diseases in pediatric population during the first year of pandemic in Chile

INTRODUCCIÓN: La pandemia por Covid-19 ha generado cambios en la atención de salud nacional, observándose en este período cambios en las causas de egresos hospitalarios (EH). OBJETIVO: Analizar el impacto del brote de Covid-19 en las causas de EH por enfermedades del Sistema Nervioso Central (ESNC) en población pediátrica durante el primer año de pandemia. MÉTODO: Estudio transversal. Análisis de base de datos del Departamento de Estadística e Información en Salud en pacientes de 0 a 18 años, comparando años 2019 y 2020. RESULTADOS: En 2020 se redujeron EH por ESNC en un 39% comparado con 2019. Disminuyeron principalmente los EH por secuelas de enfermedades inflamatorias SNC, parálisis cerebral, migraña y paraplejia/cuadriplejia, aumentando los EH por isquemia cerebral transitoria, enfermedades desmielinizantes SNC y polineuropatía inflamatoria. El número EH por ESNC mensual se correlacionó con el número de casos Covid-19 (rho -0.774, p0.003) y con la movilidad mensual del país (rho 0.928, p 0.001). CONCLUSIONES: El impacto del brote Covid-19 se asoció con reducción de EH por ESNC, disminuyeron EH por patologías crónicas y aumentaron causas agudas.

INTRODUCTION: The Covid-19 pandemic has been associated with modifications in national health care, with changes in causes of hospital discharges (HD) in this period. OBJECTIVE: To analyze the impact of the Covid-19 outbreak on causes of HD due to Central Nervous System Diseases (CNSD) in pediatric population during the first year of pandemic. METHOD: Cross-sectional study. Analysis of database of the Department of Statistics and Health Information in patients aged 0 to 18 years, comparing 2019 and 2020. RESULTS: In 2020, HD due to CNSD were reduced in 39% compared to 2019. HD causes that mainly decreased were inflammatory CNS disease sequelae, cerebral palsy, migraine and paraplegia/cuadriplegia. The HD that increased were transient cerebral ischemia, CNS demyelinating diseases and inflammatory polyneuropathy. The monthly HD due to CNSD number was correlated with the number of Covid-19 cases (rho -0.774, p0.003) and with the country's monthly mobility (rho 0.928, p 0.001). CONCLUSIONS: Covid-19 pandemic was associated with a reduction in HD due to CNSD, with decrease of EH due to chronic pathologies and increase of acute diseases

Beneficial Effects of an Integrated Psychostimulation Program in Patients with Alzheimer's Disease.

BACKGROUND: The existing pharmacological treatments for Alzheimer's disease (AD) can only slow the progression of symptoms or delay admission to long-term care facilities. The beneficial effects of non-drug treatments are poorly studied. OBJECTIVE: To describe the effects of an Integrated Psychostimulation Program (IPP) in patients with mild-moderate AD treated with acetylcholinesterase inhibitors; and to identify factors related to greater benefit of the IPP. METHODS: 206 patients (mean age = 75.9 years; MMSE = 19.6) were evaluated before starting the IPP and 3, 6, 9, and 12 months later. Measures included: Mini-Mental State Examination (MMSE), Cognitive Subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog), Rapid Disability Rating Scale (RDRS-2), and Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Patients remained cognitively stable (MMSE/ADAS-Cog) for more than 6 months and significantly worsened at 9-month and 12-month follow-ups, without clinically significant functional changes (RDRS-2) or psychiatric symptoms(NPI-Q). The mean annual change on MMSE and ADAS-Cog were 2.06 and 3.56 points, respectively, lower than the annual decline demonstrated previously in similar patients (2.4 and 4.5, respectively). 42.7% of patients maintained or improved global cognitive scores between baseline and 12-month follow-up. The patients who maintained cognitive functions were older than those who did not (77.5 versus 74.7 years). CONCLUSIONS: The IPP may be an effective treatment to maintain cognition, functionality, and psychiatric symptoms in AD patients pharmacologically treated, and older age seems to increase beneficial effects of IPP.

Do seasonal changes and climate influence the etiology of community acquired pneumonia?

INTRODUCTION: Community acquired pneumonia (CAP) is a highly prevalent pathology whose etiology is determined by the characteristics of the geographic region, and the patient. The study of these features is essential for a proper therapeutic approach. Our aim was to study the changes of the causative agent of CAP brought about by the influence of seasonal and climatic changes in our geographic area. PATIENTS AND METHOD: A prospective and longitudinal study of patients admitted with CAP was done from January 2006 to December 2009. We analyzed demographic data, comorbidities, severity, etiologic agent, complications and mortality. We correlated mean temperature and mean cumulative rainfall for each season with Streptococcus pneumoniae and Legionella pneumophila. Statistical analyses included: Chi squared test, Student's t test for independent samples, variance analysis and Spearman's correlation. RESULTS: We included 243 patients, 64.6% men and 54.7% over the age of 65. The highest incidence of CAP was in the winter. Streptococcus pneumoniae was the most common causative agent for all seasons except in summer when the main agent was Legionella pneumophila. We observed a significant correlation between the lowest seasonal average temperature and pneumococcal etiology of CAP; inversely, with higher temperatures, Legionella pneumophila was more common. No etiological differences were found by season when related with environmental humidity. CONCLUSIONS: In our area, Streptococcus pneumoniae was the most common etiological agent in winter with low temperatures; in summer, with high temperatures, the most frequent was Legionella pneumophila.

Restaurações de dentes decíduos anteriores com uso de diferentes materiais para a confecção de pinos intra-radiculares: caso clínico / Restoration in anterior primary teeth with different materials for intra canal posts: case report

Na clínica infantil, não são raras as situações em que os dentes decíduos anteriores se encontram extensamente destruídos em crianças muito jovens, que apresentam cárie de estabelecimento precoce. O presente trabalho relata o caso clínico de uma paciente de 1 ano e 9 meses que apresentava dentes incisivos superiores com porção coronária totalmente destruída e porção radicular presente. Frente ao diagnóstico clínico e radiográfico, planejou-se a retenção intra-canal com utilização de pinos para se obter a reconstrução estética e funcional desses elmentos. O plano de tratamento e sua execução incluíram Endondontia e restaurações de resina composta com o recurso de coroas de celulóide, sobre quatro diferentes tipos de pinos intra-radiculares. A reabilitação do arco anterior superior, através desta técnica, mostrou-se satisfatória e de fácil execução