La vía de la insulina y el factor de crecimiento similar a la insulina, una nueva diana terapéutica en oncología

La biología molecular del cáncer ha permitido identificar nuevas dianas para atacar las células tumorales. Recientemente se ha propuesto la vía de señalización de la insulina y el factor de crecimiento similar a la insulina como una de estas dianas. En esta revisión se describe su función biológica, los datos de laboratorio y estudios poblacionales que alertan de su papel en el cáncer y se describen los elementos claves de esta vía de señalización: los ligandos (insulina, IGF1, IGF2), sus receptores y la cascada de señales intracelular que desencadena su activación. Así mismo se revisan las distintas estrategias que se están investigando para bloquearla, algunas de las cuales ya se encuentran en estudios avanzados fase III. Los datos preliminares indican que los fármacos diseñados para bloquear esta vía pueden ser una nueva arma terapéutica para los pacientes oncológicos en un futuro próximo.The molecular biology of cancer has made it possible to identify new targets for attacking tumourous cells. One of these recently proposed targets is the insulin and insulin-like growth factor signaling pathway. This review describes its biological function, laboratory data, population studies that warn of its role in cancer, and the key elements of this signaling pathway: the ligands (insulin, IGF1, IGF2), its receptors and the cascade of intracellular signals that trigger its activation. Also reviewed are the different strategies under investigation for blocking it, some of which are already in phase III advanced studies. The preliminary data indicate that the medicines designed for blocking this pathway might be a new thera

Better adherence to the mediterranean diet could mitigate the adverse consequences of obesity on cardiovascular disease: The SUN prospective cohort

Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ¥6 points in the Trichopoulou’s Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93–2.25) for ¥25 – <30 kg/m2 of BMI and 2.00 (1.04–3.83) for ¥30 kg/m2 of BMI, compared to a BMI < 25 kg/m2. In contrast, these estimates were 0.77 (0.35–1.67) and 1.15 (0.39–3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity

Intervencionismo coronario percutáneo en Navarra. Resultados de un centro de bajo volumen intervencionista

Fundamento. El intervencionismo coronario percutáneo (PCI) es una opción terapéutica fundamental en pacientes con enfermedad coronaria. Para realizarla los especialistas deben formarse y acreditarse. Se sabe que el número de procedimientos realizados al año influye en los resultados. Pretendemos mostrar que con un bajo volumen de PCI algunos centros obtienen buenos resultados. Método. Análisis prospectivo de las características clínicas y resultados inmediatos obtenidos en nuestro centro con el PCI entre 2006 y 2012 y análisis retrospectivo de la supervivencia global, supervivencia libre de eventos y reestenosis de los PCI realizados entre 2006 y 2009. Se compararon las características clínicas, los eventos agudos y a largo plazo (complicaciones, supervivencia y mortalidad) entre nuestros pacientes y los de algunos trabajos publicados. Resultados. Nuestra probabilidad de tener cualquier complicación en un PCI fue del 9% con una mortalidad global del 2%. La mortalidad del PCI en situación estable fue del 0,43% y en el síndrome coronario agudo del 6,25%. Las complicaciones en el lugar del acceso vascular fueron del 1,44% y la incidencia de reestenosis a los nueve meses, en pacientes sometidos por primera vez a PCI, fue del 5,2%. Conclusiones. Aunque el alto volumen intervencionista ha demostrado ser importante para tener una baja tasa de complicaciones y una buena evolución a largo plazo, hay centros con bajo volumen intervencionista que por sus características pueden obtener resultados equiparables a los de alto volumen.Background. Percutaneous coronary intervention (PCI) is currently a basic therapeutic option in patients with coronary artery disease. To carry this out specialists must be trained and accredited. It is known that the number of procedures performed each year influences results. We suggest that some low volume centres may also get good results. Methods. Prospective analysis of clinical features and immediate results obtained in our centre following PCI performed between 2006 and 2012 and retrospective analysis of overall survival, outcome-free survival and restenosis in patients treated between 2006 and 2009. The clinical features, acute and long-term events (complications, survival and mortality) of our group were compared with other published studies. Results. In our centre the likelihood of complications in a PCI was 9% with an overall mortality of 2%. PCI mortality in stable coronary disease was 0.43% and in acute coronary syndrome 6.25%. Complications at the vascular access site was 1.44% and restenosis at nine months, in patients undergoing PCI for the first time, was 5.2%. Conclusions. Although a high interventionist volume has been shown to reduce the rate of complications and improve long-term evolution, some low volume interventional centres can obtain similar results to those of high volume interventional centres

Mediterranean alcohol-drinking pattern and the incidence of cardiovascular disease and cardiovascular Mortality: the SUN project

Background: We assessed the still unclear effect of the overall alcohol-drinking pattern, beyond the amount of alcohol consumed, on the incidence of cardiovascular clinical disease (CVD). Methods: We followed 14,651 participants during up to 14 years. We built a score assessing simultaneously seven dimensions of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, preference for wine, red wine consumption, wine consumed during meals and avoidance of binge drinking. Results: During 142,177 person-years of follow-up, 127 incident cases of CVD (myocardial infarction, stroke or cardiovascular mortality) were identified. Compared with the category of better conformity with the MADP, the low-adherence group exhibited a non-significantly higher risk (HR) of total CVD ((95% CI) = 1.55 (0.58–4.16)). This direct association with a departure from the traditional MADP was even stronger for cardiovascular mortality (HR (95% CI) = 3.35 (0.77–14.5)). Nevertheless, all these associations were statistically non-significant. Conclusion: Better conformity with the MADP seemed to be associated with lower cardiovascular risk in most point estimates; however, no significant results were found and more powered studies are needed to clarify the role of the MADP on CVD

Dietary inflammatory index and incidence of cardiovascular disease in the SUN cohort

BACKGROUND: Diet is known to play a key role in atherogenesis and in the development of cardiovascular events. Dietary factors may mediate these processes acting as potential modulators of inflammation. Potential Links between inflammatory properties of diet and the occurrence of cardiovascular events have not been tested previously. OBJECTIVE: We aimed to assess the association between the dietary inflammatory index (DII), a method to assess the inflammatory potential of the diet, and incident cardiovascular disease. METHODS: In the prospective, dynamic SUN cohort, 18,794 middle-aged, Spanish university graduates were followed up for 8.9 years (median). A validated 136-item food-frequency questionnaire was used to calculate the DII. The DII is based on scientific evidence about the relationship between diet and inflammatory biomarkers (C-reactive protein, IL-1β, IL-4, IL-6, IL-10 and TNF-α). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between the DII and incident cardiovascular disease (myocardial infarction, stroke or cardiovascular death). RESULTS: The risk for cardiovascular events progressively increased with each increasing quartile of DII (ptrend = 0.017). The multivariable-adjusted HR for participants in the highest (most pro-inflammatory) vs. the lowest quartile of the DII was 2.03 (95% CI 1.06-3.88). CONCLUSIONS: A pro-inflammatory diet was associated with a significantly higher risk for developing cardiovascular events

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

publishersversionPeer reviewe

Correction to: Two years later: Is the SARS-CoV-2 pandemic still having an impact on emergency surgery? An international cross-sectional survey among WSES members

Background: The SARS-CoV-2 pandemic is still ongoing and a major challenge for health care services worldwide. In the first WSES COVID-19 emergency surgery survey, a strong negative impact on emergency surgery (ES) had been described already early in the pandemic situation. However, the knowledge is limited about current effects of the pandemic on patient flow through emergency rooms, daily routine and decision making in ES as well as their changes over time during the last two pandemic years. This second WSES COVID-19 emergency surgery survey investigates the impact of the SARS-CoV-2 pandemic on ES during the course of the pandemic. Methods: A web survey had been distributed to medical specialists in ES during a four-week period from January 2022, investigating the impact of the pandemic on patients and septic diseases both requiring ES, structural problems due to the pandemic and time-to-intervention in ES routine. Results: 367 collaborators from 59 countries responded to the survey. The majority indicated that the pandemic still significantly impacts on treatment and outcome of surgical emergency patients (83.1% and 78.5%, respectively). As reasons, the collaborators reported decreased case load in ES (44.7%), but patients presenting with more prolonged and severe diseases, especially concerning perforated appendicitis (62.1%) and diverticulitis (57.5%). Otherwise, approximately 50% of the participants still observe a delay in time-to-intervention in ES compared with the situation before the pandemic. Relevant causes leading to enlarged time-to-intervention in ES during the pandemic are persistent problems with in-hospital logistics, lacks in medical staff as well as operating room and intensive care capacities during the pandemic. This leads not only to the need for triage or transferring of ES patients to other hospitals, reported by 64.0% and 48.8% of the collaborators, respectively, but also to paradigm shifts in treatment modalities to non-operative approaches reported by 67.3% of the participants, especially in uncomplicated appendicitis, cholecystitis and multiple-recurrent diverticulitis. Conclusions: The SARS-CoV-2 pandemic still significantly impacts on care and outcome of patients in ES. Well-known problems with in-hospital logistics are not sufficiently resolved by now; however, medical staff shortages and reduced capacities have been dramatically aggravated over last two pandemic years

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

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