Immune checkpoint inhibitors in endometrial cancer.

The incidence of endometrial cancer (EC) is increasing worldwide. The prognosis for patients diagnosed with early-stage remains good, whereas for patients with recurrent or metastatic disease, the prognosis is poor and treatment options, until recently, were limited. In 2017, pembrolizumab was approved by the US Food and Drug Administration (FDA) for those patients with mistmach repair deficiency (MMRd) or high microsatellite instability (MSI-H) tumors. However, only 20-30 % of EC have MSI, and just over half of these patients benefit from treatment. In 2019, the FDA granted breakthrough therapy designation to lenvatinib in combination with pembrolizumab for the potential treatment of patients with advanced microsatellite stable EC that has progressed after treatment with at least one previous systemic therapy. It appears clear that immune check-point inhibitors will have a definite place in the management of EC, both as single agent or in combination with other targeted agents. In this review, we summarize the current evidence of immune check point blockade and the identification of potential biomarkers, beyond MSI-H or MMRd, that could help to predict response to this agents in correlation with the genomic EC subtypes.

The potential to characterize ecological data with terrestrial laser scanning in Harvard Forest, MA.

Contemporary terrestrial laser scanning (TLS) is being used widely in forest ecology applications to examine ecosystem properties at increasing spatial and temporal scales. Harvard Forest (HF) in Petersham, MA, USA, is a long-term ecological research (LTER) site, a National Ecological Observatory Network (NEON) location and contains a 35 ha plot which is part of Smithsonian Institution's Forest Global Earth Observatory (ForestGEO). The combination of long-term field plots, eddy flux towers and the detailed past historical records has made HF very appealing for a variety of remote sensing studies. Terrestrial laser scanners, including three pioneering research instruments: the Echidna Validation Instrument, the Dual-Wavelength Echidna Lidar and the Compact Biomass Lidar, have already been used both independently and in conjunction with airborne laser scanning data and forest census data to characterize forest dynamics. TLS approaches include three-dimensional reconstructions of a plot over time, establishing the impact of ice storm damage on forest canopy structure, and characterizing eastern hemlock (Tsuga canadensis) canopy health affected by an invasive insect, the hemlock woolly adelgid (Adelges tsugae). Efforts such as those deployed at HF are demonstrating the power of TLS as a tool for monitoring ecological dynamics, identifying emerging forest health issues, measuring forest biomass and capturing ecological data relevant to other disciplines. This paper highlights various aspects of the ForestGEO plot that are important to current TLS work, the potential for exchange between forest ecology and TLS, and emphasizes the strength of combining TLS data with long-term ecological field data to create emerging opportunities for scientific study.

Pileflebitis como causa de fiebre / Pylephlebitis as a cause of fever

Resumen La pileflebitis o trombosis séptica portal es una complicación rara pero con gran morbilidad y mortalidad de los procesos infecciosos abdominales que drenan al sistema venoso portal. Con mayor frecuencia se relaciona con la apendicitis y diverticulitis. La incidencia ha aumentado en los últimos años con la disponibilidad de pruebas de imagen, como ecografía y tomografía axial computada abdominal. Esta facilidad en el diagnóstico y sobre todo la prescripción de antibióticos han mejorado el pronóstico, aunque no hay claro consenso en cuanto al tratamiento de esta infección y la anticoagulación es un tema controvertido.

Abstract Pylephlebitis or suppurative thrombophlebitis of the portal mesenteric venous system is a rare but deadly complication of abdominal infections drained by the portal venous system. Usually, it is seen in the setting of appendicitis and diverticulitis. The incidence have been increased in the last years because of the use of modern diagnosis imaging such as ultrasonography and computed tomography scans. The more sensitive imaging techniques and the availability of antibiotics have improve the prognosis, although there is not consensus about the empiric antibiotic regimens and the anticoagulation therapy is a controversial topic.

Causes for an Incomplete Donation Process at a Tertiary Care Hospital.

INTRODUCTION: This study aims to identify the causes for the incomplete donation process at a tertiary care hospital. MATERIALS AND METHODS: A descriptive, retrospective study was performed; all potential donors reported to the Transplant Service within the period of 2005 to 2014 were included. Descriptive statistics were used across frequencies and proportions for categorical variables, central tendency, and dispersion for continuous variables. RESULTS: The total number of deaths reported at the University Hospital (HU) was 8472, of which 815 (n = 815) were reported to COETRA ("Consejo Estatal de Trasplantes"). Among organ or tissue donors, the main known cause of death was head trauma (HT) in 26% (72). Cardiac arrest (CA) as cause of death provided the largest number of donations (141, 57%); of these, 102 (41%) were male and 39 (16%) were female. In comparison, brain death (BD) provided 104 (43%); of these, 65 (27%) were male, and 39 (16%) were female. The age interval was with a higher donation rate was 45 to 49 y (BD 18, CA 22). Donation request was not performed in 359 patients because of medical contraindication 60% (215), rapid deterioration 18% (64), and incomplete donation process 8% (27). Of 452 organ requests, 207 were not accomplished, because of body integrity 28% (57), family disagreement 20% (42), and no acceptance of BE 13% (26). CONCLUSIONS: Opportunity areas: (1) Ensure the notification of all deaths to Transplant Department for identification of potential donors; (2) Reduce rapid deterioration and raise number of completed donation protocols; (3) Increase the donation rate.

Multicenter Evaluation of a New High-Throughput HbA1c Testing Platform.

BACKGROUND: This non-interventional, multicenter study with anonymized leftover patient samples was performed to evaluate the reliability and analytical performance of the novel high-throughput HbA1c cobas c 513 analyzer. METHODS: A performance evaluation was carried out at three sites to validate the overall system functionality, user interaction and analytical performance of the new cobas c 513 analyzer using the Tina-quant® HbA1c Gen. 3 assay. RESULTS: HbA1c applications for both whole blood and hemolysate samples show a high precision using both quality control materials and pools of whole blood or hemolysates. The method comparison of HbA1c Gen. 3 on the cobas c 513 with HbA1c Gen. 2 on the Menarini HA-8180V using 249 whole blood samples shows high concordance. Moreover, analyte concentrations as measured by the cobas c 513 and Tosoh G8 and HbA1c Gen. 2 on COBAS INTEGRA® 800 CTS are comparable. CONCLUSIONS: The cobas c 513 has proven to be a reliable system with excellent analytical performance of the Tinaquant® HbA1c Gen. 3 assay in high throughput laboratories.

The Cornell Net Carbohydrate and Protein System: Updates to the model and evaluation of version 6.5.

New laboratory and animal sampling methods and data have been generated over the last 10 yr that had the potential to improve the predictions for energy, protein, and AA supply and requirements in the Cornell Net Carbohydrate and Protein System (CNCPS). The objectives of this study were to describe updates to the CNCPS and evaluate model performance against both literature and on-farm data. The changes to the feed library were significant and are reported in a separate manuscript. Degradation rates of protein and carbohydrate fractions were adjusted according to new fractionation schemes, and corresponding changes to equations used to calculate rumen outflows and postrumen digestion were presented. In response to the feed-library changes and an increased supply of essential AA because of updated contents of AA, a combined efficiency of use was adopted in place of separate calculations for maintenance and lactation to better represent the biology of the cow. Four different data sets were developed to evaluate Lys and Met requirements, rumen N balance, and milk yield predictions. In total 99 peer-reviewed studies with 389 treatments and 15 regional farms with 50 different diets were included. The broken-line model with plateau was used to identify the concentration of Lys and Met that maximizes milk protein yield and content. Results suggested concentrations of 7.00 and 2.60% of metabolizable protein (MP) for Lys and Met, respectively, for maximal protein yield and 6.77 and 2.85% of MP for Lys and Met, respectively, for maximal protein content. Updated AA concentrations were numerically higher for Lys and 11 to 18% higher for Met compared with CNCPS v6.0, and this is attributed to the increased content of Met and Lys in feeds that were previously incorrectly analyzed and described. The prediction of postruminal flows of N and milk yield were evaluated using the correlation coefficient from the BLUP (R(2)BLUP) procedure or model predictions (R(2)MDP) and the concordance correlation coefficient. The accuracy and precision of rumen-degradable N and undegradable N and bacterial N flows were improved with reduced bias. The CNCPS v6.5 predicted accurate and precise milk yield according to the first-limiting nutrient (MP or metabolizable energy) with a R(2)BLUP=0.97, R(2)MDP=0.78, and concordance correlation coefficient=0.83. Furthermore, MP-allowable milk was predicted with greater precision than metabolizable energy-allowable milk (R(2)MDP=0.82 and 0.76, respectively, for MP and metabolizable energy). Results suggest a significant improvement of the model, especially under conditions of MP limitation.

MYH polyposis syndrome: clinical findings, genetics issues and management

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk (AU)

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MYH polyposis syndrome: clinical findings, genetics issues and management.

Colorectal cancer (CRC) is one of the most frequent cancer in first world. Two hereditary CCR syndrome have been described: familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer. A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found. However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer. In addition, some authors have indicated that the spectrum of extracolonic lesions in MYH associated polyposis (MAP) might be far different from that observed in FAP and could be more similar to Lynch syndrome spectrum. In this review we are going to describe some general and specific aspects of MAP, including genetic topics, clinical features, different phenotypes and strategies to reduce CCR risk.

SEOM Clinical guidelines for the treatment of advanced colorectal cancer 2013

Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC (AU)

SEOM clinical guidelines for the treatment of advanced colorectal cancer 2013.

Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC.

Supervised daily consumption, contingent take-home incentive and non-contingent take-home in methadone maintenance.

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.

[Differences between Chicago and traditional classifications in the diagnosis of esophageal motor disorders with high-resolution manometry and topography of esophageal pressure]. / Diferencias entre las clasificaciones de Chicago y la tradicional en el diagnóstico de los trastornos motores del esófago con manometría de alta resolución y topografía de la presión esofágica.

BACKGROUND: With the introduction of high resolution manometry (HRM) and esophageal topography a novel classification (Chicago Classification) has been proposed for the diagnosis of esophageal motor disorders (EMD). Clinical differences with the traditional classification are currently under evaluation. AIM: To investigate differences between the Chicago (CC) and traditional (TC) classifications in the diagnosis of EMD. METHODS: Consecutive patients with indication for esophageal manometry were studied. HRM was performed with a 36 sensors solid-state catheter and Manoview software (V2.0).Conventional manometric tracings were analyzed by an investigator blinded to the results of HRM. Diagnosis by CC and CT were compared. RESULTS: Two hundred patients were studied, 106 (53%) of them women (53%) with a mean patient age of 43.4 (range 16 - 84) years. Preoperative evaluation for GERD 152 (76%) was the most frequent indication. Achalasia (8), scleroderma (2) and peristaltic dysfunction (60 vs. 59) were similarly diagnosed by CC and CT. Spastic disorders were more frequently identified by CC: nutcracker esophagus (NC) in 3, spastic NC in3 and segmental NC in 11 patients versus TC: NC 5. Three patients had spasm with CC and 1 with TC. Non specific motor disorder was diagnosed by TC and 2 patients had functional obstruction with CC. Hypotensive lower esophageal sphincter was identified in 63 patients with CC vs.57 with TC. CONCLUSIONS: Spastic disorders and functional obstruction were the EMD better identified by HRM and CC.

SEOM clinical guidelines for the treatment of advanced colorectal cancer

Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy (AU)

Efeito da adição de soro de leite sobre a digestibilidade aparente e os parâmetros sanguíneos de vacas secas / Effect of whey addition on apparent digestibility and blood parameters of dry cows

Avaliou-se o efeito da adição de soro de leite líquido à dieta sobre os parâmetros sanguíneos e sobre a digestibilidade aparente da matéria seca (DAMS), da proteína bruta (DAPB), da fibra em detergente neutro (DAFDN) e da fibra em detergente ácido (DAFDA) em 12 vacas Girolando, secas, que receberam feno de coastcross (Cynodon dactylon), suplementado com sal proteinado, e zero (controle), 15, 30 ou 45 litros de soro de leite/dia. A adição de soro na dieta afetou a DAMS e a DAPB (P<0,01) e não houve efeito sobre a DAFDN e a DAFDA. Quanto maior a quantidade de soro, maior o valor da DAMS e da DAPB. Os valores médios de glicose no plasma sanguíneo - 59,3; 64,0; 66,6 e 69.2mg/dL - variaram (P<0,01) entre os tratamentos, ajustando-se a regressões lineares positivas. A inclusão de soro afetou (P<0,01) a quantidade de ureia no sangue de maneira decrescente - 22,83; 20,17; 17,5 e 15,67. O soro de leite melhorou a eficiência de utilização de compostos nitrogenados no rúmen e pode ser utilizado para complementar suplementos proteicos com elevados teores de ureia.

The effect of liquid whey addition in the diet on blood parameters and on the apparent digestibility of dry matter (ADDM), crude protein (ADCP), neutral detergent fiber (ADNDF), and acid detergent fiber (ADADF) was evaluated in 12 dry Gir cows, receiving coastcross (Cynodon dactylon) hay supplemented with protein salt and zero (control), 15, 30, or 45 liters of whey per day. The inclusion of the whey in the diet affected the ADDM and ADCP (P<0.01) and had no effect on ADNDF and ADADF. As high the volume of whey inclusion, higher the ADDM and ADCP values. The average values of glucose in blood plasma - 59.3, 64.0, 66.6, and 69.2mg/dL - varied (P<0.01) among treatments, adjusting themselves to positive linear dL regressions. The whey inclusion diminished (P<0.01) blood urea values - 22.83, 20.17, 17.5, and 15.67. The whey improved the efficiency of utilization of nitrogen compounds in the rumen and can be used to complement protein supplements with high levels of urea.

[Traumatic diaphragmatic injury diagnosed preoperatively. A Case report]. / Ruptura diafragmática traumática diagnosticada preoperatoriamente. A propósito de un caso.

Traumatic diaphragmatic rupture represents a diagnostic challenge to any physician dealing with polytraumatized patients. This uncommon injury must be suspected in certain types of accidents, making knowledge of trauma mechanisms vital for its diagnosis. In this paper we present a case of traumatic diaphragmatic rupture with intrathoracic herniation of abdominal contents, which was surgically repaired. We also present a review of the clinical characteristics, diagnosis and treatment of this entity, emphasizing the importance of keeping a high index of suspicion in order to achieve a correct diagnosis.

Ruptura diafragmática traumática diagnosticada preoperatoriamente. A propósito de un caso / Traumatic diaphragmatic injury diagnosed preoperatively. A Case report

La ruptura diafragmática representa un reto diagnósticopara los médicos que se enfrentan al manejode pacientes politraumatizados. Esta lesión, aunquepoco común, debe sospecharse en ciertos tipos de accidentes,por lo cual es vital conocer su relación con lacinemática del trauma. En este trabajo presentamos uncaso de ruptura diafragmática con herniación intratorácicadel contenido abdominal que fue reparada quirúrgicamente.Así mismo hacemos una revisión del cuadroclínico, diagnóstico y tratamiento de esta patología, haciendohincapié en la importancia de mantener siempreun alto índice de sospecha para lograr un diagnósticooportuno (AU)

Traumatic diaphragmatic rupture represents adiagnostic challenge to any physician dealing with polytraumatizedpatients. This uncommon injury mustbe suspected in certain types of accidents, makingknowledge of trauma mechanisms vital for its diagnosis.In this paper we present a case of traumatic diaphragmaticrupture with intrathoracic herniation ofabdominal contents, which was surgically repaired.We also present a review of the clinical characteristics,diagnosis and treatment of this entity, emphasizing theimportance of keeping a high index of suspicion in orderto achieve a correct diagnosis (AU)

Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies

Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies (AU)