Microrna-21 and colorectal cancer

Introducción. Los microRNAs son estructuras moleculares con actividad post-transcripcional que están implicados en la regulación de la expresión genética. Diversos estudios ponen de manifiesto la participación de los microRNAs con distintas funciones fisiológicas, así como con el proceso de la oncogénesis. La expresión de los microRNAs puede verse alterada en las neoplasias por su interacción bien con los genes supresores de tumores, bien con los oncogenes. Discusión. Llevamos a cabo una revisión de la literatura sobre el microRNA-21, poniendo de manifiesto la evidencia existente entre el microRNA-21 y la enfermedad neoplásica, de forma especial con el cáncer colorrectal. Conclusiones. El estado actual de los microRNAs hace necesario continuar con la investigación existente entre la etiopatogenia de las neoplasias y los microRNAs. El conocimiento de la verdadera implicación de los microRNAs en la fisiopatología de la enfermedad neoplásica, permitirá ampliar las supuestas aplicaciones clínicas del miR-21 no sólo a la determinación del pronóstico del cáncer colorrectal, sino también desde el punto de vista diagnóstico al poder diferenciar las lesiones de la mucosa colónicaIntroduction. MicroRNAs are molecular structures with post-transcriptional activity, involved in the gene expression regulation. Several studies have demonstrated the involvement of microRNAs in different physiological functions, as well as in the oncogenesis process. The expression of microRNAs may be altered in the tumors by either interaction with tumor suppressor genes or oncogenes. Discussion. A review of the medical literature on microRNA-21 has been conducted, showing the evidence between microRNA-21 and neoplastic disease, specially with colorectal cancer. Conclusion. The current status of microRNAs makes necessary to continue the investigation of the pathogenesis of cancer and microRNAs. The knowledge of the involvement of microRNAs in the pathophysiology of neoplastic disease, will allow to extend the supposed clinical applications of miR-21 not only to the determination of the prognosis of colorectal cancer, but also for the differential diagnosis of processes of colonic mucosa

Effect of gypsum and potassium on corn yield and on the exchangeable bases of an acid soil in La Frailesca, Chiapas

Objective: To evaluate the residual effect of gypsum in corn crops 2 years after application, in a previously limed soil, as well as the result of a new addition of gypsum combined with potassium in La Frailesca, Chiapas. Design/methodology/approach: Composite factorial: initial arrangement (2017) with four levels of gypsum (0, 1.25, 2.5 and 5 t ha-1) and four levels of potassium (0, 60, 120 and 180 kg K2O ha-1). In 2019, the plots treated with gypsum were divided into two, adding the same amount of gypsum applied in 2017 to half of each of them, and leaving the other half to evaluate the residual effect to the initial treatment. The potassium doses were the same as the original ones. Corn kernel yield, pH, exchangeable bases, and percentage of aluminium saturation were measured at depths of 0 to 7 and 7 to 14 cm from groun level. Results: The greatest effect on yield was obtained with 2.5 t ha-1 of gypsum applied in 2017 without significant increases with higher gypsum doses. The exchangeable calcium content and pH increased, but the magnesium, potassium and aluminum in the soil decreased. Limitations on study/implications: The assumed of Asphalt Stain Complex was diagnosed. Findings/conclusions: The authors point out the need to be careful when recommending gypsum as an amendment; an excessive application generates an imbalance in the exchangeable potassium and magnesium of the soil, so the incorporation of these should be considered in the fertilization plan.Objective: To evaluate the residual effect of gypsum in corn crops (2 years after its application in a previously limed soil), as well as the result of a new addition of gypsum combined with potassium in La Frailesca, Chiapas, Mexico. Design/Methodology/Approach: We used a composite factorial design. The initial arrangement (2017) consisted of four levels of gypsum (0, 1.25, 2.5, and 5 t ha-1) and four levels of potassium (0, 60, 120, and 180 kg K2O ha-1). In 2019, the gypsum-treated plots were divided in half: the same amount of gypsum applied in 2017 was added to the first half and the other half was used to assess the residual effect of the initial treatment. The potassium doses were the same as the original. Corn grain yield, pH, exchangeable bases, and aluminum saturation percentage were measured at 0 to 7 and 7 to 14 cm below ground level. Results: The greatest effect on yield was obtained with 2.5 t ha-1 of gypsum applied in 2017; no significant increases were recorded with higher gypsum doses. The exchangeable calcium content and pH level increased, while magnesium, potassium, and aluminum in the soil decreased. Study Limitations/Implications: Suspected presence of Tar Spot Complex was diagnosed. Findings/Conclusions: An excessive application of gypsum generates an imbalance in exchangeable potassium and magnesium in the soil; therefore, producers must exercise caution in the use of these products as part of their fertilization plan

Idoneidad de la prescripción antibiótica en atención primaria en la Comunidad Autónoma Vasca

ObjetivoEstudiar la variabilidad e idoneidad de la prescripción antibiótica en atención primaria en la Comunidad Autónoma Vasca (CAV).DiseñoEstudio descriptivo, prospectivo.EmplazamientoCentros de atención primaria de la red reformada y no reformada de la CAV.Mediciones y resultados principalesSe estudiaron 3.182 infecciones obtenidas de consultas sobre enfermedad infecciosa mediante muestreo estratificado por área sanitaria durante febrero, marzo y abril de 1998. La idoneidad de la prescripción de antibióticos (ATB) se comparó con unos patrones elaborados tras una extensa revisión bibliográfica. Un 68,6% de las consultas son infecciones que no requieren ATB (catarro de vías altas [IRA], bronquitis aguda, gripe y gastroenteritis). Se utilizan ATB en un 28,5% de estos casos (IC, 26,6-30,5). Destaca la bronquitis aguda, con un 90,7% (IC, 87,3-93,4). La prescripción innecesaria supone un 39,7% de la prescripción total antibiótica (IC, 37,2-42,1%), suponiendo un gasto anual innecesario de 1.155 millones de pesetas.En el 31,4% de las infecciones que requieren tratamiento con ATB, se opta por uno no adecuado en un 23,7% (IC, 21-26,7%).En total, la idoneidad del tratamiento global fue del 72,2% (IC, 70,6-73,8). El hecho de trabajar en la red reformada se asoció a una mejor prescripción en todos los casos. Los pediatras prescriben mejor en el caso de las infecciones no susceptibles de tratamiento con ATB.ConclusionesLa prescripción de ATB no se realiza conforme a la evidencia científica disponible. Los tratamientos incorrectos tienen lugar sobre todo en procesos benignos y autolimitados. Es necesaria una política local de uso de ATB que incluya colaboración multidisciplinaria y formación continuada efectiva.ObjectiveTo study the variability and suitability of antibiotic prescription in primary care in the Basque Country.DesignProspective, descriptive study.SettingBasque Country health care centres both within and not in the reformed network.Measurements and main results3182 infections from consultations for infectious disease were studied through sampling stratified by health area during February, March and April 1998. The appropriateness of antibiotics (ATB) prescription was compared with some standards after an extensive bibliographic review. 68.6% of consultations were infections not needing ATB (infections of respiratory airways, acute bronchitis, flu and gastro-enteritis). ATB were used in 28.5% of these cases (CI: 26.6-30.5), especially in acute bronchitis (90.7%) (CI: 87.3-93.4). Unnecessary prescription supposes 39.7% of total antibiotic prescription (CI: 37.2-42.1%), which means unnecessary annual expenditure of 1155 million pesetas. In 31.4% of the infections that require ATB treatment, in 23.7% inappropriate treatment was chosen (CI: 21-26.7%). Overall appropriateness of treatment was 72.2% (CI: 70.6-73.8). Working in the reformed system was linked to better prescription in all cases. Paediatricians prescribed better in the case of infections not susceptible to ATB treatment.ConclusionsATB prescription is not consistent with the available scientific evidence. Incorrect treatments occur especially in benign and self-limiting processes. A local policy of ATB use that includes multi-disciplinary collaboration and effective ongoing training is necessary

Tamoxifen-elicited uterotrophy: cross-species and cross-ligand analysis of the gene expression program

<p>Abstract</p> <p>Background</p> <p>Tamoxifen (TAM) is a well characterized breast cancer drug and selective estrogen receptor modulator (SERM) which also has been associated with a small increase in risk for uterine cancers. TAM's partial agonist activation of estrogen receptor has been characterized for specific gene promoters but not at the genomic level <it>in vivo</it>.Furthermore, reducing uncertainties associated with cross-species extrapolations of pharmaco- and toxicogenomic data remains a formidable challenge.</p> <p>Results</p> <p>A comparative ligand and species analysis approach was conducted to systematically assess the physiological, morphological and uterine gene expression alterations elicited across time by TAM and ethynylestradiol (EE) in immature ovariectomized Sprague-Dawley rats and C57BL/6 mice. Differential gene expression was evaluated using custom cDNA microarrays, and the data was compared to identify conserved and divergent responses. 902 genes were differentially regulated in all four studies, 398 of which exhibit identical temporal expression patterns.</p> <p>Conclusion</p> <p>Comparative analysis of EE and TAM differentially expressed gene lists suggest TAM regulates no unique uterine genes that are conserved in the rat and mouse. This demonstrates that the partial agonist activities of TAM extend to molecular targets in regulating only a subset of EE-responsive genes. Ligand-conserved, species-divergent expression of carbonic anhydrase 2 was observed in the microarray data and confirmed by real time PCR. The identification of comparable temporal phenotypic responses linked to related gene expression profiles demonstrates that systematic comparative genomic assessments can elucidate important conserved and divergent mechanisms in rodent estrogen signalling during uterine proliferation.</p

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set

Background: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients.Methods: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method.Results: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO.Conclusions: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids

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 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). 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

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study

Purpose: To accommodate the unprecedented number of critically ill patients with pneumonia caused by coronavirus disease 2019 (COVID-19) expansion of the capacity of intensive care unit (ICU) to clinical areas not previously used for critical care was necessary. We describe the global burden of COVID-19 admissions and the clinical and organizational characteristics associated with outcomes in critically ill COVID-19 patients. Methods: Multicenter, international, point prevalence study, including adult patients with SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) and a diagnosis of COVID-19 admitted to ICU between February 15th and May 15th, 2020. Results: 4994 patients from 280 ICUs in 46 countries were included. Included ICUs increased their total capacity from 4931 to 7630 beds, deploying personnel from other areas. Overall, 1986 (39.8%) patients were admitted to surge capacity beds. Invasive ventilation at admission was present in 2325 (46.5%) patients and was required during ICU stay in 85.8% of patients. 60-day mortality was 33.9% (IQR across units: 20%–50%) and ICU mortality 32.7%. Older age, invasive mechanical ventilation, and acute kidney injury (AKI) were associated with increased mortality. These associations were also confirmed specifically in mechanically ventilated patients. Admission to surge capacity beds was not associated with mortality, even after controlling for other factors. Conclusions: ICUs responded to the increase in COVID-19 patients by increasing bed availability and staff, admitting up to 40% of patients in surge capacity beds. Although mortality in this population was high, admission to a surge capacity bed was not associated with increased mortality. Older age, invasive mechanical ventilation, and AKI were identified as the strongest predictors of mortality

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks