Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses From the KEYNOTE-826 Randomized Clinical Trial.

Importance: The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown. Objective: To assess efficacy outcomes in patient subgroups of KEYNOTE-826. Design, Setting, and Participants: Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021. Interventions: Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 [area under the free carboplatin plasma concentration vs time curve]) with or without bevacizumab, 15 mg/kg. Main Outcomes and Measures: Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score [CPS] ≥1) and in the intention-to-treat population. Results: A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations. Conclusions and Relevance: The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03635567.

First-Line Pembrolizumab + Chemotherapy Versus Placebo + Chemotherapy for Persistent, Recurrent, or Metastatic Cervical Cancer: Final Overall Survival Results of KEYNOTE-826.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The phase III, double-blind KEYNOTE-826 trial of pembrolizumab 200 mg or placebo once every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with or without bevacizumab, showed statistically significant survival benefits with the addition of pembrolizumab for patients with persistent, recurrent, or metastatic cervical cancer (primary data cutoff: May 3, 2021). This article reports the protocol-specified final overall survival (OS) results tested in the PD-L1 combined positive score (CPS) ≥1, all-comer, and CPS ≥10 populations. At the final data cutoff (October 3, 2022), the median study follow-up duration was 39.1 months (range, 32.1-46.5 months). In the PD-L1 CPS ≥1 (N = 548), all-comer (N = 617), and CPS ≥10 (N = 317) populations, median OS with pembrolizumab-chemotherapy versus placebo-chemotherapy was 28.6 months versus 16.5 months (hazard ratio [HR] for death, 0.60 [95% CI, 0.49 to 0.74]), 26.4 months versus 16.8 months (HR, 0.63 [95% CI, 0.52 to 0.77]), and 29.6 months versus 17.4 months (HR, 0.58 [95% CI, 0.44 to 0.78]), respectively. The incidence of grade ≥3 adverse events was 82.4% with pembrolizumab-chemotherapy and 75.4% with placebo-chemotherapy. These results show that pembrolizumab plus chemotherapy, with or without bevacizumab, continued to provide clinically meaningful improvements in OS for patients with persistent, recurrent, or metastatic cervical cancer.

Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In the KEYNOTE-826 study, the addition of the anti-PD-1 monoclonal antibody pembrolizumab to chemotherapy with or without bevacizumab improved overall survival and progression-free survival (primary endpoints) versus placebo plus chemotherapy with or without bevacizumab, with manageable toxicity, in patients with persistent, recurrent, or metastatic cervical cancer. In this Article, we report patient-reported outcomes (PROs) from KEYNOTE-826. METHODS: KEYNOTE-826 is a multicentre, randomised, phase 3 trial in 151 cancer treatment centres in 19 countries. Eligible patients were aged 18 years or older with persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy (previous radiosensitising chemotherapy was allowed) and not amenable to curative treatment and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) centrally by means of an interactive voice response system in a double-blind manner to receive either pembrolizumab 200 mg or placebo every 3 weeks intravenously for up to 35 cycles plus chemotherapy (paclitaxel 175 mg/m2 plus cisplatin 50 mg/m2 or carboplatin area under the curve 5 mg/mL per min, intravenously) with or without bevacizumab 15 mg/kg every 3 weeks intravenously. Randomisation (block size of 4) was stratified by metastatic disease at diagnosis, planned bevacizumab use, and PD-L1 combined positive score. Patients, investigators, and other study personnel involved in study treatment administration or clinical evaluation of patients were unaware of treatment group assignments. PRO instruments were the EORTC Quality-of-Life-Core 30 (QLQ-C30), the EORTC cervical cancer module (QLQ-CX24), and the EuroQol-5 dimension-5 level (EQ-5D-5L) visual analogue scale, each collected before treatment at cycles 1-14 and every other cycle thereafter. Primary endpoints were overall survival and progression-free survival per RECIST version 1.1 by investigator review. Change from baseline in QLQ-C30 global health status (GHS)-quality of life (QoL) was a prespecified secondary endpoint and was assessed in the PRO full analysis population (all patients who received at least one dose of study treatment and completed at least one post-baseline PRO assessment). Other PRO analyses were protocol-specified exploratory endpoints. The study is registered with ClinicalTrials.gov, NCT03635567, and is ongoing. FINDINGS: Between Nov 20, 2018, and Jan 31, 2020, of 883 patients screened, 617 were randomly assigned (pembrolizumab group, n=308; placebo group, n=309). 587 (95%) of 617 patients received at least one dose of study treatment and completed at least one post-baseline PRO assessment and were therefore included in the PRO analyses (pembrolizumab group, n=290; placebo group, n=297). Median follow-up was 22·0 months (IQR 19·1-24·4). At week 30, QLQ-C30 completion was 199 (69%) of 290 patients in the pembrolizumab group and 168 (57%) of 297 patients in the placebo group; compliance was 199 (94%) of 211 and 168 (90%) of 186, respectively. The least squares mean change in QLQ-C30 GHS-QoL score from baseline to week 30 was -0·3 points (95% CI -3·1 to 2·6) in the pembrolizumab group and -1·3 points (-4·2 to 1·7) in the placebo group, with a between-group difference in least squares mean change of 1·0 point (95% CI -2·7 to 4·7). Median time to true deterioration in GHS-QoL was not reached (NR; 95% CI 13·4 months-NR) in the pembrolizumab group and 12·9 months (6·6-NR) in the placebo group (hazard ratio 0·84 [95% CI 0·65-1·09]). 122 (42%) of 290 patients in the pembrolizumab group versus 85 (29%) of 297 in the placebo group had improved GHS-QoL at any time during the study (p=0·0003). INTERPRETATION: Addition of pembrolizumab to chemotherapy with or without bevacizumab did not negatively affect health-related quality of life. Along with the efficacy and safety results already reported from KEYNOTE-826, these data support the benefit of pembrolizumab and the value of immunotherapy in patients with recurrent, persistent, or metastatic cervical cancer. FUNDING: Merck Sharp & Dohme.

Impact of acetylation process of kraft lignin in development of environment-friendly semisolid lubricants.

The aim of this work was to study the influence of the acetylation process of kraft lignin on developing dispersions potentially applicable as new bio-based semisolid lubricants. Lignin was functionalized with acetic anhydride and pyridine as a catalyst by modifying different reaction variables (temperature, ratio of pyridine/acetic anhydride and time). Acetylated lignin was analyzed using FTIR, 1H and 13C NMR techniques, TGA, DSC and SEM to evaluate the chemical, morphological and thermal changes induced by the acetylation process. The influence of the acetylation process on the rheological and tribological properties of dispersions was related to the development of different microstructures, which depend on chemical and morphological properties of acetylated lignin. In this sense, two different rheological behaviours (gel-like or fluid-like) were found to depend on the reaction time. From the experimental results obtained, it can be concluded that the acetylation process is a key issue to modulate rheological and morphological properties of dispersions, resulting in an effective method to improve the compatibility of lignin and castor oil. Acetylated lignin with medium degrees of substitution with adequate morphological properties can be potentially used as an effective thickening agent to develop semisolid lubricants.

Concordance in psychopharmacological treatment before and after first mental health consultation.

PURPOSE: To analyse concordance between treatment prescribed before and after the first mental health consultation. We understand concordance in two different senses: first, as a similar amount of equivalent doses and drug type; second, as a similar treatment for each patient. METHOD: This is an analytical, descriptive, retrospective study on psychopharmacological treatment before and after first mental health consultation of 1236 patients. Drugs were classified into four groups and the equivalent dose respect to reference medication was considered in each group in order to make a comparison between primary and mental health. RESULTS: Moderate concordance was found in prescribed treatments before and after first mental health consultation (except antidepressants). The average number of benzodiazepines decreased, as did average doses prescribed at mental health consultation respect to previously prescribed treatment; average doses of antidepressants, however, increased. From the patient's perspective, dose increase was more frequent than decrease. Nevertheless, a high percentage of polymedicated patients were found, although this percentage decreased after the first mental health consultation. CONCLUSION: There exists a moderate concordance between the pharmacological treatment prescribed before and after the first mental health consultation. However, the use of benzodiazepines diminished significantly after the first consultation, mainly due to a decrease in the percentage of polymedicated patients.

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer.

BACKGROUND: Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding pembrolizumab to chemotherapy with or without bevacizumab. METHODS: In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis. RESULTS: In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively). CONCLUSIONS: Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.).

Portable single-lead electrocardiogram device is accurate for QTc evaluation in hospitalized patients.

BACKGROUND: Many commonly used drugs can prolong the QTc interval (QTc), which can lead to potentially life-threatening arrhythmias. In the current era of the COVID-19 pandemic, it is worth mentioning that the disease itself and several drugs used for its treatment have been associated with QTc prolongation. OBJECTIVE: To evaluate the agreement and clinical precision of a portable single-lead electrocardiogram (ECG) device to measure the QTc interval compared to the standard 12-lead ECG. METHODS: In sequential tests, QTc of ECG recordings obtained with the KardiaMobile (KM-1L) device (AliveCor, San Francisco, CA) were compared to QTc obtained with conventional 12-lead ECG. Agreement was evaluated using Bland-Altman plots and Lin's concordance coefficient. Consistency between the 2 devices in determining QTc prolongation (QTc ≥470 ms in males or ≥480 ms in females) was evaluated with kappa statistics. RESULTS: A total of 128 patients with a presumed or confirmed diagnosis of COVID-19 admitted to a university hospital were included. QTc intervals measured with KM-1L were similar to QTc measured with conventional ECG (442.45 ± 40.5 vs 441.65 ± 40.3 ms, P = .15). Bland-Altman analysis showed no significant difference in QTc values (average difference of -0.797, 95% limits of agreement:-13.179; 11.585). Lin's concordance coefficient showed an excellent agreement (0.988, P < .001). Concordance between the 2 devices for determining QTc prolongation was excellent (kappa >0.90). CONCLUSION: ECG recordings obtained with KM-1L allow an accurate QTc interval assessment. Considering its simplicity of use, this approach has advantages over conventional ECG and can provide an alternative for the evaluation of QTc in hospitalized patients, during the current time of the COVID-19 pandemic and beyond.

Promoción de la salud a través de prácticas claves en la atención integrada a las enfermedades prevalentes de la infancia (AIEPI), en profesores de educación prebásica / Health promotion through key practices in integrated attention to prevalent childhood illnesses (IMCI), in pre-basic education teachers

Introducción: la estrategia de atención integrada a las enfermedades prevalentes de la infancia (AIEPI), avanza en el concepto de integralidad de la atención de la salud, siendo una herramienta práctica, en los servicios de salud y hogar, establece máxima validez a las preocupaciones de la comunidad y del personal de salud. Objetivo: conocer la promoción de la salud a través de prácticas claves en la atención integrada a las enfermedades prevalentes de la infancia (AIEPI), en profesores de educación prebásica. Material y métodos: investigación descriptiva en población de 59 técnicos y profesionales adscritos a jardines infantiles y salas cuna, en la ciudad de Temuco, que corresponden a 23 salas cuna, que ejercen actividades laborales con lactantes de 6-12 meses. Recolección de información, y instrumento de prácticas claves propuestas por AIEPI OMS/OPS, el análisis se trabajó con estadística descriptiva e inferencia estadística, apoyándose en el software SPSS versión 24 en español. La investigación cumplió los criterios de rigor ético de Ezequiel Emanuel y la aprobación del Comité de Ética acreditado de la Universidad Mayor. Resultados: 59 personas, de sexo femenino, personal de atención en la guardería de jardines infantiles y salas cuna. La edad promedio de 40 años, promedio de 8 años de ejercicio técnico profesional. El 78% del personal de atención en la guardería, posee una jornada laboral de 9 horas diarias. Respecto a las conductas en lactancia materna un 78 %, "siempre" realiza fomento del amamantamiento y un 72,9 % "siempre" fomenta los beneficios de la lactancia materna; no obstante, en cuanto al fomento de la técnica de acople, "a veces" fomenta la técnica un 39,8 %. De la inmunización un 64,4 % del personal parvulario, "siempre fomenta la vacunación del PNI", por otro lado, un 71 % de la muestra "siempre fomenta la administración de vacunas de campaña (influenza)". De la conducta por cuadro respiratorio, un 69,5 % de la población, "siempre reconoce los signos y síntomas que alertan de un cuadro respiratorio". Conclusión: en la comunidad educativa, el uso de la estrategia desarrolla un actuar más efectivo, identificando actitudes de promoción. El tener la posibilidad de contacto diario; permite a la comunidad de prebásica dirigir su mirada hacia los problemas más relevantes y proponer estrategias para la solución en conexión con el sector salud

Introduction: the strategy of Integrated Attention to Prevalent Childhood Diseases (IMCI), advances in the concept of comprehensive health care, being a practical tool, in health and home services, giving maximum validity to concerns of the community and health personnel. Objective: to know the promotion of health through key practices in Integrated Attention to Prevalent Childhood Illnesses (IMCI), in pre-basic education teachers. Material and Methods: Descriptive research in a population of 59 technicians and professionals assigned to Kindergartens and Nursery Rooms, in the city of Temuco, corresponding to 23 Nursery Rooms, who carry out work activities with infants aged 6-12 months. Information collection and key practices instrument proposed by IMCI WHO / PAHO. The analysis was carried out with descriptive statistics and statistical inference, relying on the SPSS software version 24 in Spanish. The research met the criteria of ethical rigor of Ezequiel Emanuel and the approval of the accredited Ethics Committee of the Universidad Mayor. Results: 59 people, female, nursery care personnel from Kindergartens and Nursery Rooms. The average age of 40 years, average of 8 years of professional technical practice. 78% of the kindergarten staff have a 9-hour workday. Regarding breastfeeding behaviors, 78% "always" promote breastfeeding and 72.9% "always" promote the benefits of breastfeeding, however, regarding the promotion of the coupling technique, "a times", 39.8% promote the technique. Of the immunization, 64.4% of the kindergarten staff "always promote the PNI vaccination", on the other hand, 71% of the sample "always promote the administration of field vaccines (Influenza)". Of the behavior due to respiratory symptoms, 69.5% of the population "always recognize the signs and symptoms that warn of a respiratory condition". Conclusion: in the educational community, the use of the strategy develops a more effective action, identifying attitudes of promotion. Having the possibility of daily contact; allows the pre-basic community to direct its gaze towards the most relevant problems and propose strategies for the solution in connection with the health sector.

Analysis of Consultation Demand in a Mental Health Centre during the Recent Economic Recession.

The economic recession that recently affected most European countries has led to a worsening of the mental health situation in the general population and an associated rise in outpatient psychiatric care. The aim of this study was to analyse the socio-demographic, clinical and assistential features of the demand for specialist mental health attention. A descriptive and analytical study was conducted in the period 2011-2015 (N = 1252). The principal relations among variables were analysed by an χ2 test, followed by a Z test with Bonferroni's correction. For a global perspective a Multiple Correspondence Analysis was performed. 2 The most frequent disorders were adjustment, anxiety and mood disorders, and in addition there were a large number of patients without diagnosis. The percentage of unemployed or inactive patients was high, as it was for those with a low academic level. The younger patients were more prone to have adjustment disorders, especially among the unemployed ones, while anxiety disorders were more frequent in the patients with jobs. A close association seems to exist between unemployment, low academic level and mental health problems. The high demand for mental health attention reveals a clear need to optimize the utilization of specialized care in mental health.

Association of leptin receptor expression in placenta and peripheral blood mononuclear cell with maternal weight in birth outcomes.

INTRODUCTION: The pregnancy period represents the most intense period of growth and development. Pre-pregnancy weight influences weight gain during pregnancy. Leptin is a hormone mainly derived from white adipose tissue, during pregnancy leptin is also produced by the placenta. It has been suggested that the effects of placental leptin on the mother may contribute to endocrine-mediated alterations in energy balance; a dysregulation in leptin levels or its receptors may lead to poor birth outcomes. Therefore, the main goal of the present study was to analyze the differences in birth outcomes by maternal weight with the expression level of leptin receptor in maternal peripheral blood mononuclear cell (PBMC) and placental tissue. METHODS: Women with full-term gestation and its offspring were enrolled. Total RNA from maternal PBMC and placenta was obtained to perform the analysis of expression of the leptin receptor (LEPR) gene trough real-time PCR technique. Data were analyzed using one-way ANOVA or Mann-Whitney u test when applicable. Pearson correlation coefficient was used to determine the relationship between continuous variables (Stata v.13); p ≤ 0.05 was considered statistically significant. RESULTS: No statistically significant differences were found between LEPR expression level and the BMI studied groups in maternal PBMC and placental tissue. Interaction between gestational weight gain (GWG) and LEPR in maternal PBMC explain in a 32% the variability of the newborn weight. CONCLUSIONS: LEPR expression level in maternal PBMC correlates with newborn measurements independent from sex. GWG can affect fetal development by increasing fetal birth weight.

Actividad antifúngica del aceite volátil de Hedyosmum sp, frente a especies del género Candida / Antifungal activity of the volatile oil of Hedyosmum sp, Against species of the genus Candida

El objetivo del estudio fue determinar la actividad antifúngica del aceite volátil de las partes aéreas de la especie vegetal Hedyosmum sp., frente al complejo Candida albicans, C. glabrata, C. tropicalis y C. parapsilosis. El material vegetal se recolectó del bosque natural Jacarón, Provincia de Chimborazo, Ecuador. La extracción del aceite volátil se realizó por hidrodestilación, obteniéndose un rendimiento de 0,09%. La actividad antifúngica fue estudiada mediante el método de difusión en agar y los resultados se interpretaron mediante detección-medición de halos de inhibición y concentración mínima inhibitoria. El estudio se realizó partiendo del aceite puro y diluciones con dimetil sulfóxido. Los resultados se validaron mediante controles positivos (Fluconazol) y negativos (dimetil sulfóxido). El aceite puro mostró actividad antifúngica frente a C. albicans, C. tropicalis, C. parapsilosis, pero no frente a C. glabrata. Mientras que, la actividad antifúngica determinada empleando diluciones del aceite permitió establecer la concentración mínima inhibitoria para C. tropicalis, C. parapsilosis, en 0,25x106 µg/mL y para C. albicans en 0,5x106 µg/mL. Estos resultados concluyeron que el aceite volátil de Hedyosmum sp., presenta actividad antifúngica poco significativa frente a tres de las cuatro especies de Candida estudiadas

The objective of the study was to determine the antifungal activity of the volatile oil of the aerial parts of the plant species Hedyosmum sp., against Candida albicans, C. glabrata, C. tropicalis and C. parapsilosis complex. The plant material was collected from the Jacarón natural forest, Chimborazo Province, Ecuador. The extraction of the essential oil was carried out by hydro-distillation, obtaining a yield of 0.09%. Antifungal activity was studied by means of the diffusion in agar method and the results were interpreted by detection-measurement of inhibition halos and minimum inhibitory concentration. The study was carried out starting from the pure oil and dilutions with dimethyl sulfoxide. The results were validated by positive controls (Fluconazole) and negative controls (dimethyl sulfoxide). The pure oil showed antifungal activity against C. albicans, C. tropicalis, and C. parapsilosis complex, but not against C. glabrata. While, the antifungal activity determined using dilutions of the oil allowed establishing the minimum inhibitory concentration for C. tropicalis, C. parapsilosis complex, at 0,25x106 µg/mL and for C. albicans at 0,5x106 µg/mL. These results concluded that the volatile oil of Hedyosmum sp., Presents little antifungal activity against three of the four Candida species studied

Recuperación mejorada después de cirugía torácica: ERAS / Enhanced recovery after thoracic surgery

Resumen El concepto de Recuperación Mejorada Después de Cirugía, Enhanced recovery after Surgery (ERAS), engloba una serie de protocolos para el manejo perioperatorio optimizado en diversas patologías quirúrgicas. Los objetivos de estos protocolos son: mejorar los resultados quirúrgicos, disminuir las complicaciones, reducir los días de hospitalización, disminuir los costos asociados a la intervención y, finalmente, favorecer una rehabilitación más rápida. Para una correcta aplicación de estos protocolos, se requiere la interacción y el trabajo de un equipo multidisciplinario. En este artículo, se realizará una puesta al día de las intervenciones más importantes de los procesos perioperatorios de la cirugía torácica.

The concept of ERAS includes a series of optimized perioperative management protocols in various surgical pathologies. The objectives of these protocols are: improve surgical results, reduce complications, reduce length of in-hospital stay, reduce the associated health care costs and finally, favor a more rapid rehabilitation. For the correct application of these protocols, the interaction and work of a multidisciplinary team is required. In this article, an update will be made of the most important interventions in the perioperative processes of thoracic surgery.

The Paradox of Self-Fertile Varieties in the Context of Self-Incompatible Genotypes in Olive.

Olive, representing one of the most important fruit crops of the Mediterranean area, is characterized by a general low fruit yield, due to numerous constraints, including alternate bearing, low flower viability, male-sterility, inter-incompatibility, and self-incompatibility (SI). Early efforts to clarify the genetic control of SI in olive gave conflicting results, and only recently, the genetic control of SI has been disclosed, revealing that olive possesses an unconventional homomorphic sporophytic diallelic system of SI, dissimilar from other described plants. This system, characterized by the presence of two SI groups, prevents self-fertilization and regulates inter-compatibility between cultivars, such that cultivars bearing the same incompatibility group are incompatible. Despite the presence of a functional SI, some varieties, in particular conditions, are able to set seeds following self-fertilization, a mechanism known as pseudo-self-compatibility (PSC), as widely reported in previous literature. Here, we summarize the results of previous works on SI in olive, particularly focusing on the occurrence of self-fertility, and offer a new perspective in view of the recent elucidation of the genetic architecture of the SI system in olive. Recent advances in research aimed at unraveling the molecular bases of SI and its breakdown in olive are also presented. The clarification of these mechanisms may have a huge impact on orchard management and will provide fundamental information for the future of olive breeding programs.

Virulence factors and clinical patterns of multiple-clone hypermucoviscous KPC-2 producing K. pneumoniae.

Carbapenemase-producing Klebsiella pneumoniae (CRKP) are increasingly reported worldwide being necessary the local epidemiological monitoring. Our aim was to characterize the hypermucoviscous CRKP isolates collected in our hospital during a 6 months period. Carriage of the carbapenemase genes (bla KPC, bla NDM, bla VIM and bla OXA-48), extended spectrum ß-lactamases (bla SHV-2, bla CTX-M) and the virulence genes (magA, k2A, rmpA, wabG, uge, allS, entB, ycfM, kpn, wcaG, fimH, mrkD, iutA, iroN, hly and cnf-1) were determined by multiplex-PCR. Genetic relationship among the isolates was performed by PFGE and MLST. A total of 35 isolates were recovered, being the urinary and respiratory tract the most common infection sites (34.2%). The bla KPC-2 gene was present in all the isolates, coexisting with bla CTX-M-2 (45.7%), bla SHV-2 (28.6%), and bla CTX-M-2/bla SHV-2 (14.3%). The capsular serotype K2 corresponded with 68.6% of the isolates. Virulence factors frequency were variable [adhesins (97.1%), siderophores (94.3%) and phagocytosis resistance (wabG 48.5%, uge 80% and ycfM 57.1%)]. A total of 10 STs were identified although 40% of them clustered on ST25-CC65, and 17% to ST17. The incidence of KPC-2-producing K. pneumoniae reported by the hospital was 0.290 per 1000 admissions. In summary we described an epidemic scenario of multidrug resistant hypermucoviscous KPC-2 producing ST25 K. pneumoniae in our institution.

An overview of environmental arsenic issues and exposure risks in Uruguay.

Evidence for low-dose health effects of Arsenic (As) in humans is still controversial and presents a major public health issue in several countries worldwide. It is not clear yet, whether there is a lower safe threshold for arsenic in drinking water among other possible sources such as food, below which, exposures are not harmful. In Uruguay, safe drinking water is supplied to 94% of the population by a state company (OSE) and As levels in workplaces and food are officially regulated. This paper aims to present and discuss the issues regarding arsenic exposure risks to the environment and human population, which are being addressed in a multidisciplinary manner in Uruguay since 2007. An overview is given on both the background and the current situation, presenting reports and research studies conducted on these problems by various academic, state, and private institutions that deal with regulations, surveillance, and health care. Scientific research on geogenic As levels in groundwater indicates As levels above those recommended by the WHO for drinking water (10 µg L-1) in different Uruguayan aquifers. There is a lack of baseline studies concerning Uruguayan residents that are exposed to As in drinking water over time. Furthermore, there is a need for data on environmental chemical exposure that could be associated with disease or death in the country. In addition, only a few As risk exposure assessment studies in children, adults, and workers using biomarkers in urine are available. Furthermore, this paper presents As levels in a rice growing region and the spatial distribution of groundwater arsenic data compared to a national cancer atlas database as ongoing research advances. Multidisciplinary research projects and local future actions are also described. This contribution constitutes a first attempt to develop a feasible health risk assessment of low-dose arsenic exposure in this Latin-American country.

Experiencia de unidad de dolor agudo perioperatorio del hospital Gustavo Fricke, enero - abril 2019 / Areview of the perioperative pain management unit, Gustavo Fricke Hospital, january - april 2019

Introducción: Se puede definir dolor como una experiencia sensorial o emocional desagradable asociada a un daño real o potencial en un tejido. El dolor agudo postoperatorio mal controlado aumenta la morbimortalidad al impactar sobre múltiples sistemas. Para abordar este problema se han creado unidades encargadas de manejar el dolor perioperatorio, conformadas por equipos multidisciplinarios. Objetivos: El objetivo general de esta revisión es presentar el funcionamiento y la experiencia a la fecha de la Unidad del Dolor Agudo Perioperatorio (UDAP) del Hospital Gustavo Fricke (HGF) a los distintos servicios. Desarrollo: La Unidad del Dolor Agudo Perioperatorio (UDAP) del HGF se gesta dentro de la unidad de anestesia y pabellones quirúrgicos en enero del año 2018.Son cerca de 30 pacientes mensuales los que se incluyen en la unidad, los que en promedio están 2 días con algún tipo de analgesia avanzada. Estos pacientes han sido sometidos a cirugías de distintas especialidades, siendo la cirugía digestiva la más frecuente, seguido de la ginecológica y traumatológica. Conclusión: La UDAP del HGF es una iniciativa que nace buscando garantizarla evaluación y seguimiento adecuado de los pacientes sometidos a intervenciones quirúrgicas. La experiencia a la fecha ha sido satisfactoria, no obstante, existen aspectos a mejorar y que constituyen los desafíos a mediano y largo plazo de la unidad.

Introduction: Pain may be defined as an unpleasant sensory or emotional experience associated with real or potential tissue damage. Poorly managed acute post-operatory pain affects multiple systems and increases mortality and morbidity. To address this issue, pain management units have been created for the management of perioperative pain by multidisciplinary teams. Objectives: The general objective of this review is to describe the functioning and experience to date of the Acute Perioperative Pain Unit (UDAP) in Gustavo Fricke Hospital (HGF). Development: Gustavo Fricke Hospital´s Acute Perioperative Pain Unit has been administered by the operating theatre and anaesthesia unit since January 2018. Around 30 patients are seen per month. They receive step 3 pain relief and the average length of stay is 2 days. The patients undergo surgeries from the various specialties, gastrointestinal surgery being the most frequent, followed by gynecological and traumatological. Conclusion: The Gustavo Fricke Hospital Acute Perioperative Pain Unit arose from the need to guarantee adequate evaluation and follow-up of surgical patients. To date the experience has been satisfactory, however some aspects could be improved and these constitute medium and long term challenges for the unit.

Experiencia de unidad de dolor agudo perioperatorio del hospital Gustavo Fricke, enero - abril 2019 / A review of the perioperative pain management unit, Gustavo Fricke Hospital, january - april 2019

Introducción: Se puede definir dolor como una experiencia sensorial o emocional desagradable asociada a un daño real o potencial en un tejido. El dolor agudo postoperatorio mal controlado aumenta la morbimortalidad al impactar sobre múltiples sistemas. Para abordar este problema se han creado unidades encargadas de manejar el dolor perioperatorio, conformadas por equipos multidisciplinarios. Objetivos: El objetivo general de esta revisión es presentar el funcionamiento y la experiencia a la fecha de la Unidad del Dolor Agudo Perioperatorio (UDAP) del Hospital Gustavo Fricke (HGF) a los distintos servicios. Desarrollo: La Unidad del Dolor Agudo Perioperatorio (UDAP) del HGF se gesta dentro de la unidad de anestesia y pabellones quirúrgicos en enero del año 2018. Son cerca de 30 pacientes mensuales los que se incluyen en la unidad, los que en promedio están 2 días con algún tipo de analgesia avanzada. Estos pacientes han sido sometidos a cirugías de distintas especialidades, siendo la cirugía digestiva la más frecuente, seguido de la ginecológica y traumatológica. Conclusión: La UDAP del HGF es una iniciativa que nace buscando garantizar la evaluación y seguimiento adecuado de los pacientes sometidos a intervenciones quirúrgicas. La experiencia a la fecha ha sido satisfactoria, no obstante, existen aspectos a mejorar y que constituyen los desafíos a mediano y largo plazo de la unidad.

Introduction: Pain may be defined as an unpleasant sensory or emotional experience associated with real or potential tissue damage. Poorly managed acute post-operatory pain affects multiple systems and increases mortality and morbidity. To address this issue, pain management units have been created for the management of perioperative pain by multidisciplinary teams. Objectives: The general objective of this review is to describe the functioning and experience to date of the Acute Perioperative Pain Unit (UDAP) in Gustavo Fricke Hospital (HGF). Development: Gustavo Fricke Hospital´s Acute Perioperative Pain Unit has been administered by the operating theatre and anaesthesia unit since January 2018. Around 30 patients are seen per month. They receive step 3 pain relief and the average length of stay is 2 days. The patients undergo surgeries from the various specialties, gastrointestinal surgery being the most frequent, followed by gynecological and traumatological. Conclusion: The Gustavo Fricke Hospital Acute Perioperative Pain Unit arose from the need to guarantee adequate evaluation and follow-up of surgical patients. To date the experience has been satisfactory, however some aspects could be improved and these constitute medium and long term challenges for the unit.