Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial.

Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need. Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater. Design, Setting, and Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017. Interventions: Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks. Main Outcomes and Measures: Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater. Results: A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02; P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively. Conclusions and Relevance: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested. Trial Registration: ClinicalTrials.gov Identifier: NCT02494583.

Plant characterization of genetically modified maize hybrids MON-89Ø34-3 × MON-88Ø17-3, MON-89Ø34-3 × MON-ØØ6Ø3-6, and MON-ØØ6Ø3-6: alternatives for maize production in Mexico.

Environmental risk assessment (ERA) of genetically modified (GM) crops is a process to evaluate whether the biotechnology trait(s) in a GM crop may result in increased pest potential or harm to the environment. In this analysis, two GM insect-resistant (IR) herbicide-tolerant maize hybrids (MON-89Ø34-3 × MON-88Ø17-3 and MON-89Ø34-3 × MON-ØØ6Ø3-6) and one herbicide-tolerant GM hybrid (MON-ØØ6Ø3-6) were compared with conventional maize hybrids of similar genetic backgrounds. Two sets of studies, Experimental Phase and Pilot Phase, were conducted across five ecological regions (ecoregions) in Mexico during 2009-2013, and data were subject to meta-analysis. Results from the Experimental Phase studies, which were used for ERA, indicated that the three GM hybrids were not different from conventional maize for early stand count, days-to-silking, days-to-anthesis, root lodging, stalk lodging, or final stand count. Statistically significant differences were observed for seedling vigor, ear height, plant height, grain moisture, and grain yield, particularly in the IR hybrids; however, none of these phenotypic differences are expected to contribute to a biological or ecological change that would result in an increased pest potential or ecological risk when cultivating these GM hybrids. Overall, results from the Experimental Phase studies are consistent with those from other world regions, confirming that there are no additional risks compared to conventional maize. Results from Pilot Phase studies indicated that, compared to conventional maize hybrids, no differences were detected for the agronomic and phenotypic characteristics measured on the three GM maize hybrids, with the exception of grain moisture and grain yield in the IR hybrids. Since MON-89Ø34-3 × MON-88Ø17-3 and MON-89Ø34-3 × MON-ØØ6Ø3-6 confer resistance to target insect pests, they are an alternative for farmers in Mexico to protect the crop from insect damage. Additionally, the herbicide tolerance conferred by all three GM hybrids enables more cost-effective weed management.

Pollen-Mediated Gene Flow in Maize: Implications for Isolation Requirements and Coexistence in Mexico, the Center of Origin of Maize.

Mexico, the center of origin of maize (Zea mays L.), has taken actions to preserve the identity and diversity of maize landraces and wild relatives. Historically, spatial isolation has been used in seed production to maintain seed purity. Spatial isolation can also be a key component for a strategy to minimize pollen-mediated gene flow in Mexico between transgenic maize and sexually compatible plants of maize conventional hybrids, landraces, and wild relatives. The objective of this research was to generate field maize-to-maize outcrossing data to help guide coexistence discussions in Mexico. In this study, outcrossing rates were determined and modeled from eight locations in six northern states, which represent the most economically important areas for the cultivation of hybrid maize in Mexico. At each site, pollen source plots were planted with a yellow-kernel maize hybrid and surrounded by plots with a white-kernel conventional maize hybrid (pollen recipient) of the same maturity. Outcrossing rates were then quantified by assessing the number of yellow kernels harvested from white-kernel hybrid plots. The highest outcrossing values were observed near the pollen source (12.9% at 1 m distance). The outcrossing levels declined sharply to 4.6, 2.7, 1.4, 1.0, 0.9, 0.5, and 0.5% as the distance from the pollen source increased to 2, 4, 8, 12, 16, 20, and 25 m, respectively. At distances beyond 20 m outcrossing values at all locations were below 1%. These trends are consistent with studies conducted in other world regions. The results suggest that coexistence measures that have been implemented in other geographies, such as spatial isolation, would be successful in Mexico to minimize transgenic maize pollen flow to conventional maize hybrids, landraces and wild relatives.

Beneficial regulation of matrix metalloproteinases for skin health.

Matrix metalloproteinases (MMPs) are essential to the remodeling of the extracellular matrix. While their upregulation facilitates aging and cancer, they are essential to epidermal differentiation and the prevention of wound scars. The pharmaceutical industry is active in identifying products that inhibit MMPs to prevent or treat aging and cancer and products that stimulate MMPs to prevent epidermal hyperproliferative diseases and wound scars.

A visual query-by-example image database for chest CT images: potential role as a decision and educational support tool for radiologists.

Primary reading or further evaluation of diagnostic imaging examination often needs a comparison between the actual findings and the relevant prior images of the same patient or similar radiological data found in other patients. This support is of clinical importance and may have significant effects on physicians' examination reading efficiency, service-quality, and work satisfaction. We developed a visual query-by-example image database for storing and retrieving chest CT images by means of a visual browser Image Management Environment (IME) and tested its retrieval efficiency. The visual browser IME included four fundamental features (segmentation, indexing, quick load and recall, user-friendly interface) in an integrated graphical environment for a user-friendly image database management. The system was tested on a database of 2000 chest CT images, randomly chosen from the digital archives of our institutions. A sample of eight heterogeneous images were used as queries and, for each of them a team of three expert radiologists selected the most similar images from the database (a set of 15 images containing similar abnormalities in the same position of the query). The sensitivity and the positive predictive factor, both averaged over the 8 test queries and 15 answers, were respectively 0.975 and 0.91 The IME system is currently under evaluation at our institutions as an experimental application. We consider it a useful work-in-progress tool for clinical practice facilitating searches for a variety of radiological tasks.

Valoración de la glucemia e hidratación previa en pacientes gestantes sometidas a un bloqueo central / Evaluation of glycemia and prior hydration in pregnant women undergoing central blocking

Introducción: La hipoglucemia puede causar serios problemas en la paciente anestesiada prematuramente sin indagar la glucemia del momento previo a la realización del bloqueo central, porque se le bloquearían los mecanismos compensatorios con la consecuente hipotensión arterial. Objetivos: 1.- Reconocer la importancia de los métodos físicos para evitar el Síndrome de compresión aorto-cava en embarazadas a término. 2. Valorar la glucemia, la hidratación y la estabilidad hemodinámica previamente a la realización del bloqueo central. Material y Método: Cesáreas programadas y de urgencia. ASA I-II con ayuno superior a 6 horas. Corrección de la hipoglucemia (<59 mg/dl) con 8-10 ml de dextrosa 25 por ciento, 20 minutos antes del bloqueo. Prevención de la hipotensión arterial mediante el desplazamiento manual del útero, posición de Trendelemburg, y, corrección con bolos de efedrina. Resultados: 5 por ciento de las pacientes presentaron hipoglucemia (53ñ7) mg/dl) p=0,001 y 10 por ciento hipotensión arterial. No hubo diferencia entre las glucemias de las mujeres hipotensas y no hipotensas. Precarga promedio: 383 ml. El total de líquido administrado (1.275 ml) fue menor al necesario para cubrir las pérdidas insensibles (1.412 ml). Conclusión: Es infrecuente la incidencia de hipoglucemia en las cesáreas. Preferimos las maniobras físicas de descompresión aorto-cava y la hidratación racional al uso indiscriminado de vasopresores y a la precarga tradicional. (AU)

Valoración de la glucemia e hidratación previa en pacientes gestantes sometidas a un bloqueo central / Evaluation of glycemia and prior hydration in pregnant women undergoing central blocking

Introducción: La hipoglucemia puede causar serios problemas en la paciente anestesiada prematuramente sin indagar la glucemia del momento previo a la realización del bloqueo central, porque se le bloquearían los mecanismos compensatorios con la consecuente hipotensión arterial. Objetivos: 1.- Reconocer la importancia de los métodos físicos para evitar el Síndrome de compresión aorto-cava en embarazadas a término. 2. Valorar la glucemia, la hidratación y la estabilidad hemodinámica previamente a la realización del bloqueo central. Material y Método: Cesáreas programadas y de urgencia. ASA I-II con ayuno superior a 6 horas. Corrección de la hipoglucemia (<59 mg/dl) con 8-10 ml de dextrosa 25 por ciento, 20 minutos antes del bloqueo. Prevención de la hipotensión arterial mediante el desplazamiento manual del útero, posición de Trendelemburg, y, corrección con bolos de efedrina. Resultados: 5 por ciento de las pacientes presentaron hipoglucemia (53ñ7) mg/dl) p=0,001 y 10 por ciento hipotensión arterial. No hubo diferencia entre las glucemias de las mujeres hipotensas y no hipotensas. Precarga promedio: 383 ml. El total de líquido administrado (1.275 ml) fue menor al necesario para cubrir las pérdidas insensibles (1.412 ml). Conclusión: Es infrecuente la incidencia de hipoglucemia en las cesáreas. Preferimos las maniobras físicas de descompresión aorto-cava y la hidratación racional al uso indiscriminado de vasopresores y a la precarga tradicional.

Radiotherapy-related fatigue.

Radiotherapy-induced fatigue is a common early and chronic side-effect of irradiation, reported in up to 80 and 30% of patients during radiation therapy and at follow-up visits, respectively. It is frequently underestimated by medical and nursing staff, only about 50% of patients discuss it with a physician and in one fourth of cases any intervention is proposed to the patient. The patients rarely expect fatigue to be a side-effect of treatment. The etiology of this common symptom, its correlates and prevalence are poorly understood. In numerous studies the level and time course of fatigue was demonstrated to depend on the site of tumor and treatment modalities. For example, psychological mechanisms have been proposed to explain fatigue in women receiving irradiation for early breast cancer, whereas decline in neuromuscular efficiency rather than psychological reasons can lead to the fatigue observed in patients undergoing radiotherapy for prostate cancer. Fatigue can affect global quality of life more than pain, sexual dysfunction and other cancer- or treatment-related symptoms. Several interventions have been tested in the management of radiotherapy-related fatigue and some randomized studies have been recently published. Although an optimal method has not yet been established, some promising results have been reported with relaxation therapy, group psychotherapy, physical exercise and sleep. Further methodologically correct studies are warranted to define better the causes, optimal prevention and management of this symptom.