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Rationale Some patients with chronic obstructive pulmonary disease (COPD) suffer accelerated lung function (FEV1) decline over time. OBJECTIVE: To investigate the relationship between chronic bronchial infection (CBI) and, in particular, the isolation of Pseudomonas aeruginosa (PA), and FEV1 decline in COPD. METHODS: Post-hoc analysis of a prospective cohort of 201 COPD patients followed up every 3-6 months for 84 months. CBI was defined as =3 sputum positive cultures of the same pathogenic micro-organism (PPM) over 1 year. Patients were stratified according to the presence of CBI by any PPM, as well by a single or multiple isolation of PA during follow-up. An adjusted mixed-effects linear regression model was used to investigate the independent effects of CBI and PA isolation on FEV1 decline over time. RESULTS: During follow-up, PPMs were never isolated in 43.3% of patients, in 23.9% of them PPMs were isolated once, and CBI by any PPM was confirmed in 32.8% of participants. FEV1 decline in the entire cohort was 33.7 (95%CI: 21.4 to 46.1) ml/year. This was significantly increased in patients with CBI by any PPM (57.1 (95%CI: 28.5-79.3) ml/year) and in those in whom PA was isolated at least once (48.5 (95%CI 27.3-88.2) ml/year). Multivariable analysis showed that the presence of both CBI by any PPM, and at least one PA isolation, were independent factors associated with faster FEV1 decline adjusted by baseline FEV1, presence of bronchiectasis, body mass index, age, exacerbations, smoking status, symptoms, baseline treatment and comorbidities. CONCLUSIONS: The presence of CBI by any PPM, and one or more PA isolation, were independently associated with FEV1 decline in COPD patients.

Background: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods: Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models. Results: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG). Conclusions: In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation. The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant n° proyectos RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R + D + I and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER)”. This work was supported by the Instituto de Salud Carlos III projects AC17/00019, PI18/00154, ICI20/00058, CIBER de Enfermedades Infecciosas, and Gilead Sciences (Investigator Sponsored Research ISR-17-10192). The funders had no role in the study design, data analysis, or in the interpretation of the results. Sí

The isolation of Pseudomonas aeruginosa (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased mortality. Yet, factors associated with first PA sputum isolation, and PA persistence have not been investigated before. The objective of the present study was to investigate risk factors for new acquisition and persistence of PA infection and their relationship with all-cause mortality in patients with COPD. Post-hoc analysis of prospectively collected cohort of 170 COPD patients (GOLD II-IV) who were free of previous PA isolation and followed up every 3-6 months for 85 [50.25-110.25] months. PA was isolated for the first time in 41 patients (24.1%) after 36 [12-60] months of follow-up. Risk factor for first PA isolation were high cumulative smoking exposure, severe airflow limitation, previous severe exacerbations, high fibrinogen levels and previous isolation of Haemophilus Influenzae. PA was isolated again one or more times during follow-up in 58.5% of these patients. This was significantly associated with the presence of CT bronchiectasis and persistence of severe exacerbations, whereas the use of inhaled antibiotic treatment after the first PA isolation (at the discretion of the attending physician) reduced PA persistence. During follow-up, 79 patients (46.4%) died. A single PA isolation did not increase mortality, but PA persistence did (HR 3.06 [1.8-5.2], p = 0.001). We conclude that PA occurs frequently in clinically stable COPD patients, risk factors for a first PA isolation and PA persistence are different, and the latter (but not the former) is associated with increased all-cause mortality.

The length of hospital stay ( LOS ) for acute pulmonary embolism ( PE ) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown.

The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known.

[EN]: [Background]: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE. [Methods]: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3–6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4 h/day) were compared with those with not adherent or those who had not been prescribed CPAP. [Results]: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96–2.7; p = 0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07–15.1; p = 0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2–11.6; p = 0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05–1.02; p = 0.053). [Conclusions]: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events., [ES]: [Antecedentes]: Existe cierta controversia sobre el efecto de la presión positiva continua en las vías respiratorias (CPAP) sobre la incidencia de eventos cardiovasculares (ECV). Sin embargo, no se ha evaluado la incidencia de ECV en los pacientes con apnea obstructiva del sueño (AOS) e hipertensión resistente (HR). Nuestro objetivo fue analizar el efecto a largo plazo del tratamiento con CPAP en pacientes con HR y AOS en la incidencia de ECV. [Métodos]: Estudio multicéntrico, observacional y prospectivo de pacientes con AOS y HR. Cada paciente acudió a revisión cada 3-6 meses y se midió la incidencia de ECV. Se compararon los pacientes con buena adherencia a la CPAP (al menos 4 h/día) con aquellos con mala adherencia o aquellos a quienes no se les había indicado la CPAP. [Resultados]: Se obtuvieron datos válidos de 163 pacientes con 64 eventos de ECV. Se ofreció tratamiento con CPAP al 82%. Después de 58 meses de seguimiento, el 58,3% de los pacientes presentaron buena adherencia a la CPAP. Los pacientes con mala adherencia o sin prescripción de CPAP presentaron un aumento no significativo en la incidencia total de ECV (HR: 1,6; IC 95%: 0,96-2,7; p = 0,07). Un análisis de sensibilidad mostró que los pacientes con mala adherencia a la CPAP tuvieron un aumento significativo en la incidencia de eventos cerebrovasculares (HR: 3,1; IC 95%: 1,07-15,1; p = 0,041) y crisis hipertensivas (HR: 5,1; IC 95%: 2,2-11,6; p = 0,006), pero la tendencia fue en la dirección opuesta con respecto a los eventos coronarios (HR: 0,22; IC 95%: 0,05-1,02; p = 0,053). [Conclusiones]: En pacientes con HR y AOS moderada o grave, un tratamiento ineficaz con CPAP mostró una tendencia hacia un aumento en la incidencia de ECV (particularmente eventos neurovasculares y crisis hipertensivas), sin ningún cambio con respecto a los eventos coronarios.

Background: There is some controversy about the effect of continuous positive airway pressure (CPAP) on the incidence of cardiovascular events (CVE). However, the incidence of CVE among patients with both obstructive sleep apnea (OSA) ans resistant hypertension (HR) has not been evaluated. Our objective was to analyze the long-term effect of CPAP treatment in patients with RH and OSA on the incidence of CVE. Methods: Multi-center, observational and prospective study of patients with moderate-severe OSA and RH. All the patients were followed up every 3-6 months and the CVE incidence was measured. Patients adherent to CPAP (at least 4h/day) were compared with those with not adherent or those who had not been prescribed CPAP. Results: Valid data were obtained from 163 patients with 64 CVE incidents. Treatment with CPAP was offered to 82%. After 58 months of follow-up, 58.3% of patients were adherent to CPAP. Patients not adherent to CPAP presented a non-significant increase in the total CVE incidence (HR:1.6; 95%CI: 0.96-2.7; p=0.07). A sensitivity analysis showed that patients not adherent to CPAP had a significant increase in the incidence of cerebrovascular events (HR: 3.1; CI95%: 1.07-15.1; p=0.041) and hypertensive crises (HR: 5.1; CI95%: 2.2-11.6; p=0.006), but the trend went in the opposite direction with respect to coronary events (HR: 0.22; CI95%: 0.05-1.02; p=0.053). Conclusions: In patients with RH and moderate-severe OSA, an uneffective treatment with CPAP showed a trend toward an increase in the incidence of CVE (particularly neurovascular events and hypertensive crises) without any changes with respect to coronary events.

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm. Funding for this study was provided by Instituto de Salud Carlos III (ISCIII) (Fondos FEDER and Plan Estatal de IþDþI 2013-2016 [PI14-01176 and PI17-01001], 2018-2021 [PI18/00382], and PT17/0015/0006]) and the iLUNG Program (B2017/BMD-3884) from the Comunidad de Madrid. Ventana Medical Systems provided the clone SP384 free of charge. Thermo Fisher Scientific provided the Oncomine Dx Target Test panel free of charge. Dr. F. Lopez-Rios thanks T. Crean for his constant support.

Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at, Quintero and colleagues show that relatives of colorectal cancer patients have a higher risk of themselves developing the disease, as well as neoplasias. Screening guidelines should be accordingly adjusted., Editors' Summary Background Colorectal cancer kills about 700,000 people worldwide every year. This common cancer develops when one of the epithelial cells that lines the colon (the final part of the digestive system; also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquires genetic changes that allow it to divide uncontrollably to form a tumor (lump), to invade surrounding tissues, and to move around the body (metastasize). Symptoms of colorectal cancer include weight loss, blood in the stool, and changed bowel habits. Treatments for the condition include surgery, chemotherapy, and radiation. As with all types of cancer, these treatments are more likely to be successful if started when the tumor is small and before it has invaded surrounding tissues. Consequently, many countries run screening programs to detect the earliest signs of colorectal cancer in apparently healthy people. Why Was This Study Done? One of the methods used to screen for colorectal cancer is colonoscopy—visual examination of the colonic lining using a tube-like instrument that is inserted through the rectum into the colon. Colonoscopy also detects adenomas (polyps), benign tumors that lack the ability to invade or metastasize. It is important to find and remove adenomas because these growths can develop into colorectal cancers. In the United States, colonoscopy is recommended every 10 y for everyone in the general population over 50 y old. However, the first-degree relatives (parents, siblings, or child) of patients with colorectal cancer have a higher risk of developing colorectal cancer than people in the general population. So, current screening guidelines in the US and elsewhere recommend colonoscopy every 5 or 10 y from age 40 for people who have a first-degree relative diagnosed with colorectal cancer, depending on whether the relative’s colorectal cancer was diagnosed before or after the age of 60, respectively. Notably, no large-scale studies have compared the risk of adenomas in symptom-free people with first-degree relatives with colorectal cancer with the risk in symptom-free average-risk people. This large multicenter cross-sectional study (a study that looks at a single time point) aims to remedy this deficit in the evidence base. What Did the Researchers Do and Find? The researchers enrolled 3,015 first-degree relatives of patients with colorectal cancer and 3,038 average-risk individuals, all of whom were undergoing their first screening colonoscopy in Spain. They divided the familial-risk cohort into two groups. The 1-FDR group comprised people with one first-degree relative diagnosed with colorectal cancer at ≥60 y or at

El trasplante renal (Tx) representa el tratamiento de elección para los pacientes con enfermedad renal crónica avanzada (ERC), pero la escasez de órganos disponibles para aquellos con gran comorbilidad puede incrementar significativamente la mortalidad en enfermos candidatos a Tx. Esto constituye un problema sanitario preocupante, dado el incremento de los pacientes incidentes y prevalentes con ERC, especialmente de aquellos con ERC secundaria a entidades de gran comorbilidad como la diabetes y la hipertensión arterial. Asimismo, este hecho puede incrementar el número de pacientes en lista de espera (LE) y disparar sus cifras de mortalidad. Por tanto, actualmente resulta pertinente identificar las causas de muerte y los factores de riesgo de mortalidad en esta población, conocer las barreras que limitan el acceso al Tx y aplicar modelos predictivos de mortalidad en aras de mejorar los resultados de estos enfermos en términos de supervivencia. En esta revisión sobre la mortalidad de los pacientes en LE se abordarán los siguientes aspectos: 1) la magnitud de este problema y la importancia de algunos datos epidemiológicos; 2) los factores de riesgo de mortalidad en estos enfermos y las barreras que existen para el acceso al Tx que pudieran incrementar la mortalidad en esta población; 3) evaluación del riesgo de muerte de los pacientes en diálisis a partir de la comorbilidad; y 4) valoración de la mortalidad en LE mediante análisis de regresión de riesgos competitivos y la generación de un modelo de riesgo compuesto, incluyendo la comorbilidad y otros factores urémicos.

Participants in three international cohort studies on mechanical ventilation (1998, 2004 and 2010). National coordinators recruited local investigators from eligible intensive care units. The research ethics board of each participating institution approved the protocol and need for informed consent was according to local rules.

Participants in three international cohort studies on mechanical ventilation (1998, 2004 and 2010). National coordinators recruited local investigators from eligible intensive care units. The research ethics board of each participating institution approved the protocol and need for informed consent was according to local rules.