Liraglutide Improves Forced Vital Capacity in Individuals With Type 2 Diabetes: Data From the Randomized Crossover LIRALUNG Study

To evaluate the effect of liraglutide, a glucagon-like peptide 1 receptor agonist, on pulmonary function and serum levels of surfactant protein D (SP-D) in type 2 diabetes. A double-blind, randomized, crossover, placebo-controlled clinical trial comprising 76 patients with a baseline forced expiratory volume in 1 s <90% of that predicted. Liraglutide was administered for 7 weeks (2 weeks of titration plus 5 weeks at 1.8 mg daily). This short duration was intentional to minimize weight loss as a potential confounding factor. Serum level of SP-D was used as a biomarker of alveolar-capillary barrier integrity. Liraglutide exerted a positive impact on forced vital capacity (FVC) in comparison with placebo (ΔFVC 5.2% of predicted [from 0.8 to 9.6]; P = 0.009). No differences in the other pulmonary variables were observed. Participants under liraglutide treatment also experienced a decrease in serum SP-D (P = 0.038). The absolute change in FVC correlated with final serum SP-D in participants receiving liraglutide (r = −0.313, P = 0.036). Stepwise multivariate regression analysis showed that final serum SP-D independently predicted changes in FVC. In conclusion, liraglutide increased FVC in patients with type 2 diabetes. This effect was associated with a significant decrease of circulating SP-D, thus pointing to a beneficial effect in the alveolar-capillary function.CIBERDEM and CIBEROBN are initiatives of Instituto de Salud Carlos III (PI 15/00260 and PI 18/00964). The drugs under study were supplied by Novo Nordisk at the request of the sponsor of the study expressly for the clinical trial, with Novo Nordisk taking responsibility for the manufacture, packaging, and labeling

The influence of sleep apnea syndrome and intermittent hypoxia in carotid adventitial vasa vasorum

Subjects with sleep apnea-hypopnea syndrome (SAHS) show an increased carotid intima-media thickness. However, no data exist about earlier markers of atheromatous disease, such as the proliferation and expansion of the adventitial vasa vasorum (VV) to the avascular intima in this setting. Our aim was to assess carotid VV density and its relationship with sleep parameters in a cohort of obese patients without prior vascular events. A total of 55 subjects evaluated for bariatric surgery were prospectively recruited. A non-attended respiratory polygraphy was performed. The apnea-hypopnea index (AHI) and the cumulative percentage of time spent with oxygen saturation below 90% (CT90) were assessed. Serum concentrations of soluble intercellular adhesion molecule 1, P-selectin, lipocalin-2 and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. Contrast-enhanced carotid ultrasound was used to assess the VV density. Patients with SAHS (80%) showed a higher adventitial VV density (0.801±0.125 vs. 0.697±0.082, p = 0.005) and higher levels of sVCAM-1 (745.2±137.8 vs. 643.3±122.7 ng/ml, p = 0.035) than subjects with an AHI lower than 10 events/hour. In addition, a positive association exist between mean VV density and AHI (r = 0.445, p = 0.001) and CT90 (r = 0.399, p = 0.005). Finally, in the multiple linear regression analysis, female sex, fasting plasma glucose and AHI (but not CT90) were the only variables independently associated with the mean adventitial VV density (R2 = 0.327). In conclusion, a high VV density is present in obese subjects with SAHS, and chronic intermittent hypoxia is pointed as an independent risk factor for the development of this early step of atheromatous diseaseThis study was supported by grants from Instituto de Salud Carlos III (Fondo de Investigación Sanitaria PI15/00260), European Union (European Regional Development Fund, Fondo Europeo de Desarrollo Regional, “Una manera de hacer Europa”), Fundación Sociedad Española Endocrinología y Nutrición (FSEEN) and Laboratorios Almirall (“Beca FSEEN de ayuda a la investigación sobre factores de riesgo cardiovascular”, Laboratorio ESTEVE and Menarini Spain S.A. CIBER de Diabetes y Enfermedades Metabólicas Asociadas and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank Virtudes Maria and Mª del Valle Peña (from the Unit for the Detection and Treatment of Atherothrombotic Diseases), Olga Mínguez and Lidia Pascual (from the Sleep Unit) for their help in the study

Effects of Mediterranean Diet and Physical Activity on Pulmonary Function: A Cross-Sectional Analysis in the ILERVAS Project

A few studies showed that both adherence to Mediterranean diet (MedDiet) and physical activity practice have a positive impact on pulmonary function in subjects with lung disease. These associations are not well studied in subjects free from lung disease. In a cross-sectional study conducted in 3020 middle-aged subjects free of lung disease, adherence to the MedDiet using the Mediterranean Diet Adherence Screener, and physical activity practice using the International Physical Activity Questionnaire short form were recorded. Respiratory function was assessed using forced spirometry and the results were evaluated according to the Global initiative for Chronic Obstructive Lung Disease. Logistic regression models were used to analyze the associations between adherence to the MedDiet and physical activity practice with the presence of ventilatory defects. Participants with a high adherence to MedDiet, in comparison to those with low adherence, had both higher forced vital capacity (FVC; 100 (87–109) vs. 94 (82–105) % of predicted, p = 0.003) and forced expired volume in the first second (FEV1; 100 (89–112) vs. 93 (80–107) % of predicted, p < 0.001). According to their degree of physical activity, those subjects with a high adherence also had both higher FVC (100 (88–107) vs. 94 (83–105) % of predicted, p = 0.027) and FEV1 (100 (89–110) vs. 95 (84–108) % of predicted, p = 0.047) in comparison with those with low adherence. The multivariable logistic regression models showed a significant and independent association between both low adherence to MedDiet and low physical activity practice, and the presence of altered pulmonary patterns, with differences between men and women. However, no joint effect between adherence to MedDiet and physical activity practice on respiratory function values was observed. Low adherence to MedDiet and low physical activity practice were independently associated with pulmonary impairment. Therefore, the lung mechanics seem to benefit from heart-healthy lifestyle behaviors.This study was supported by grants from the Diputació de Lleida, Generalitat de Catalunya (2017SGR696 and SLT0021600250), Instituto de Salud Carlos III (Fondo de Investigación Sanitaria PI12/00803 and PI15/00260), and European Union (European Regional Development Fund, Fondo Europeo de Desarrollo Regional, “Una manera de hacer Europa”). CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBER de Nutrición y Obesidad, and CIBER de Enfermedades Respiratorias are initiatives of the Instituto de Salud Carlos III

Predicting Alzheimer's disease CSF core biomarkers: a multimodal Machine Learning approach

IntroductionAlzheimer's disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require a lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative sleep electroencephalography features as potential non-invasive biomarkers of AD pathology. However, quantitative analysis of comprehensive polysomnography (PSG) signals remains relatively understudied. PSG is a non-invasive test enabling qualitative and quantitative analysis of a wide range of parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest for its ability to discern intricate patterns within complex datasets, offering promise in AD neuropathology detection. Therefore, this study aims to evaluate the effectiveness of a multimodal ML approach in predicting core AD CSF biomarkers.MethodsMild-moderate AD patients were prospectively recruited for PSG, followed by testing of CSF and blood samples for biomarkers. PSG signals underwent preprocessing to extract non-linear, time domain and frequency domain statistics quantitative features. Multiple ML algorithms were trained using four subsets of input features: clinical variables (CLINVAR), conventional PSG parameters (SLEEPVAR), quantitative PSG signal features (PSGVAR) and a combination of all subsets (ALL). Cross-validation techniques were employed to evaluate model performance and ensure generalizability. Regression models were developed to determine the most effective variable combinations for explaining variance in the biomarkers.ResultsOn 49 subjects, Gradient Boosting Regressors achieved the best results in estimating biomarkers levels, using different loss functions for each biomarker: least absolute deviation (LAD) for the Aβ42, least squares (LS) for p-tau and Huber for t-tau. The ALL subset demonstrated the lowest training errors for all three biomarkers, albeit with varying test performance. Specifically, the SLEEPVAR subset yielded the best test performance in predicting Aβ42, while the ALL subset most accurately predicted p-tau and t-tau due to the lowest test errors.ConclusionsMultimodal ML can help predict the outcome of CSF biomarkers in early AD by utilizing non-invasive and economically feasible variables. The integration of computational models into medical practice offers a promising tool for the screening of patients at risk of AD, potentially guiding clinical decisions

Prospective validation of the CLIP score: a new prognostic system for patient with cirrhosis and hepatocellular carcinoma

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage, As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with RCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection

Diferencias según sexo y edad de la tasa de mortalidad por tromboembolia pulmonar en España desde 1999 a 2021

Peer reviewe

Age-period-cohort effect on lung cancer mortality in Spain, 1982-2021

[Background] The aim of the study is to provide up-to-date information and evaluate the age-period-cohort effects of age-period cohorts on lung cancer (LC) mortality in Spain for the period 1982 to 2021.[Methods] We analysed deaths by LC and population for the period 1982–2021, available from the Spanish National Institute of Statistics. The LC corresponds to code 162 and codes C33 and C34 of the 9th and 10th editions of the International Classification of Diseases, respectively. Age-period-cohort (A-P-C) modelling was applied to compute the net drift, local drift, longitudinal age curve, and rate ratios (RR) of each period and cohort. A-P-C analysis was performed using the A-P-C Web Tool provided by the National Cancer Institute of the United States.[Results] Estimated relative risk in the male birth cohorts has followed a steady downward trend in all cohorts born since 1922, showing an initial period (1922–1947) of slight decline, followed by a more marked decrease in the cohorts born during the period 1947–1977. In the younger cohorts (1977–1997), the decline appears to have stabilised. In women, a strong cohort effect is observed. In those born after the Spanish Civil War (1936 to 1939), the risk increased until it peaked in the 1960s, after which it started to decrease with the same intensity. Period RR in men decreased from 1987 to 1991 (1.1) to 2017–2021 (0.6), while period RR in women increased during this time (from 0.8 to 1.6).[Conclusions] The cohort effect observed in women born after the Civil War suggests that the onset of the LC epidemic may have been due to a higher prevalence of women smokers in these cohorts. However, the trend observed in the younger cohorts suggests a possible slowing-down in the increase in mortality risk in the following years.Peer reviewe

Chronic obstructive pulmonary disease mortality trends in Spain, 1980-2020

© 2023, Korean Society of Epidemiology. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.[OBJECTIVES] In Spain, there has been a recent increase in the mortality rate for chronic obstructive pulmonary disease (COPD) in younger women. This study aimed to analyze trends in the COPD mortality rate in Spain from 1980 to 2020, evaluating any differences between genders and age groups.[METHODS] Death certificates and mid-year population data were obtained from the Spanish National Institute of Statistics. For both genders, age group-specific and standardized (overall and truncated) rates were calculated by the direct method using the world standard population. The data were analyzed using the joinpoint regression method.[RESULTS] In both men and women, the number of COPD deaths increased from 1980 to 1999 (average annual increase of 7% in men and 4% in women), while from 1999 onwards, deaths decreased by -1.0% per year in both genders. In women, there was a significant final period of increase in the 55-59 to 70-74 age groups and a slowing of the decline in the over 75 age group. Additionally, an increase in mortality for the truncated rates was observed for women between 2006 and 2020. In men under 70 years of age, there was an initial period in which death rates remained stable or significantly increased, followed by a period in which they decreased significantly.[CONCLUSIONS] Our study shows age and gender differences in COPD mortality trends in Spain. Although the data show a downward trend, we have identified a worrying increase in the truncated rates in women for the last few years.Peer reviewe

Chronic obstructive pulmonary disease mortality trends in Spain, 1980-2020

OBJECTIVES In Spain, there has been a recent increase in the mortality rate for chronic obstructive pulmonary disease (COPD) in younger women. This study aimed to analyze trends in the COPD mortality rate in Spain from 1980 to 2020, evaluating any differences between genders and age groups. METHODS Death certificates and mid-year population data were obtained from the Spanish National Institute of Statistics. For both genders, age group-specific and standardized (overall and truncated) rates were calculated by the direct method using the world standard population. The data were analyzed using the joinpoint regression method. RESULTS In both men and women, the number of COPD deaths increased from 1980 to 1999 (average annual increase of 7% in men and 4% in women), while from 1999 onwards, deaths decreased by -1.0% per year in both genders. In women, there was a significant final period of increase in the 55-59 to 70-74 age groups and a slowing of the decline in the over 75 age group. Additionally, an increase in mortality for the truncated rates was observed for women between 2006 and 2020. In men under 70 years of age, there was an initial period in which death rates remained stable or significantly increased, followed by a period in which they decreased significantly. CONCLUSIONS Our study shows age and gender differences in COPD mortality trends in Spain. Although the data show a downward trend, we have identified a worrying increase in the truncated rates in women for the last few years