Gastrointestinal Stromal Tumor (GIST) and its relationship with germline mutations

We present the case of a 38-year-old man with a history of abdominal paraganglioma 10 years ago, who consulted for hematemesis and asthenia of 5 days' evolution. An upper gastrointestinal endoscopy was performed where a raised submucosal lesion, about 2 cm, with ulceration on its surface, was observed at the corporal-antral junction. The CT scan revealed nodular thickening of the gastric wall at the level of the lesser curvature. After the resolution of his hematemesis, it was decided to intervene on the patient, performing a partial gastrectomyUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Oligodendrocyte metabolism throughout its differentiation: immunocytochemistry study and its impact in remyelination

Introduction: Oligodendrocytes (OL) role in demyelinating pathologies such as multiple sclerosis and other neurodegenerative diseases is only recently being subject of extensive research. While the genetic and molecular aspects have been thoroughly studied, their metabolism was overshadowed. In order to develop new therapies to promote remyelination of already damaged axons, we need to accurately describe how OL metabolism affects axon myelination and trophic support (1). The objective of this study is to obtain cytological evidence of the extent of both glycolytic metabolism and oxidative phosphorylation by immunocytochemistry throughout the development of OL. Methods: Oligodendroglia cells from post-natal mice cortices were obtained and cultured. A wide assortment of differentiation-stage-specific cell surface antigens, a glycolytic and an oxidative phosphorylation marker were combined in several immunofluorescences to study both metabolic pathways in each step of differentiation. Results: After analysing them under confocal microscopy and imaging software, we observed a constant upregulation of glycolytic metabolism throughout differentiation, while oxidative phosphorylation seemed to increase with differentiation to then decrease when oligodendrocytes achieved their final maturation stage. Conclusions: Therefore, oxidative phosphorylation may be crucial in the differentiation of precursors and glycolysis would thus be the preferred metabolic pathway for fully matured OL. [1] Rosko L. et al. Neuroscientist. 2019;25(4):334–43.Supported by UMA and IBIMA and funding from two ongoing projects: - ‘Modulation of oligodendrocyte metabolism via blood vessel remodelling as target to promote remyelination’ (funding by NEURATRIS). - ‘Blood vessel remodelling modulates remyelination by oligodendrocyte metabolic reprogramming’ (funding by Arsep Foundation). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Gastrointestinal cancer: Relationship between histology and microbiota

Este trabajo fue presentado como comunicación tipo póster en el citado congreso.Objectives: Review of the published literature concerning the relationship between microbiome and gastrointestinal cancer. Methods: Present work is focused on systematic research in the most prominent biomedical databases finds relevant works in Pubmed and the library’s catalog of the University of Málaga (Jábega) of published journals in the last 5 years. Results: In this work, the mechanisms used by the microbiome to damage gastrointestinal epithelial cells and cause cancer are explained. Some of them are the dysbiosis, destruction of the mucosal barrier, chronic inflammation, damage caused by metabolites produced in the digestion and the direct attack of certain toxins to the cell’s DNA. These mechanisms adjust the immune response, by activation or inhibition using different cytokines. There is also a deeper look into several microorganisms and how they cause gastrointestinal cancer using toxins or virulence factors to activate them. Conclusions: The evidence found so far about the microbiota and gastrointestinal cancer is enough to assume the relationship between them, although there is much left to research. With these findings, it can be expected that in a near future certain microorganisms could be used for screening purposes, due to their increase in early stages of the tumor genesis and also, in a preventive way to try to eradicate them, even avoid cancer. Studies on the microbiota are hardly beginning, and results appear to be promising.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Ilustración del proceso constructivo de vías primarias, secundarias y terciarias basado en las especificaciones técnicas de construcción de carreteras del Instituto Nacional de vías (INVIAS)

: figuras, tablas ; 28 cmEsta cartilla metodológica describe a través de ilustraciones el proceso constructivo de vías primarias, secundarias y terciarias, basado en las especificaciones técnicas de construcción de carreteras del Instituto Nacional de Vías (INVIAS)PregradoIngeniero CivilIngeniería Civi

Development of a prediction model for postoperative pneumonia A multicentre prospective observational study

BACKGROUND Postoperative pneumonia is associated with increased morbidity, mortality and costs. Prediction models of pneumonia that are currently available are based on retrospectively collected data and administrative coding systems. OBJECTIVE To identify independent variables associated with the occurrence of postoperative pneumonia. DESIGN A prospective observational study of a multicentre cohort (Prospective Evaluation of a RIsk Score for postoperative pulmonary COmPlications in Europe database). SETTING Sixty-three hospitals in Europe. PATIENTS Patients undergoing surgery under general and/or regional anaesthesia during a 7-day recruitment period. MAIN OUTCOME MEASURE The primary outcome was postoperative pneumonia. Definition: the need for treatment with antibiotics for a respiratory infection and at least one of the following criteria: new or changed sputum; new or changed lung opacities on a clinically indicated chest radiograph; temperature more than 38.3 degrees C; leucocyte count more than 12 000 mu l(-1). RESULTS Postoperative pneumonia occurred in 120 out of 5094 patients (2.4%). Eighty-two of the 120 (68.3%) patients with pneumonia required ICU admission, compared with 399 of the 4974 (8.0%) without pneumonia (P < 0.001). We identified five variables independently associated with postoperative pneumonia: functional status [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.58 to 3.12], pre-operative SpO(2) values while breathing room air (OR 0.83, 95% CI 0.78 to 0.84), intra-operative colloid administration (OR 2.97, 95% CI 1.94 to 3.99), intra-operative blood transfusion (OR 2.19, 95% CI 1.41 to 4.71) and surgical site (open upper abdominal surgery OR 3.98, 95% CI 2.19 to 7.59). The model had good discrimination (c-statistic 0.89) and calibration (Hosmer-Lemeshow P = 0.572). CONCLUSION We identified five variables independently associated with postoperative pneumonia. The model performed well and after external validation may be used for risk stratification and management of patients at risk of postoperative pneumonia

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)