Search

Over the past century, definitive management of unresectable cervical cancer has evolved and currently employs high-dose radiation treatment with teletherapy and intracavitary brachytherapy (ICBT) components, combined with concurrent chemotherapy. Reflecting high disease prevalence among developing nations, the International Federation of Gynecology and Obstetrics (FIGO) staging of cervical cancer relies on clinical assessment, with limited radiographic studies. However, multiple clinicopathologic analyses describe suboptimal correlation between clinical examination findings and pathologic stage. Over the past two decades, systematic evaluation of volumetric and functional imaging modalities including CT, MRI, and PET-CT has refined our ability to define disease extent and provide posttreatment surveillance. Similarly, traditional ICBT techniques relied on two-dimensional (2D) data for evaluation of target dose coverage and offered limited assessment of exposure to critical structures including the bladder, rectum, and sigmoid colon. During the last several years, investigators at leading European centers have enhanced the capabilities of existing ICBT techniques through dose optimization [high-dose rate (HDR) and pulsed dose rate (PDR)] and by incorporating volumetric imaging methods. Early results are encouraging, from both toxicity and tumor control perspectives. These techniques are currently being adopted in multiple centers. Pertinent aspects are summarized in the body of this report.

Case report We report a case of a 35-year-old male patient with no medical history, who experienced decreased vision in his left eye that he noticed by chance. After a complete ophthalmic examination, he was diagnosed with congenital retinal macrovessel with macular thickening. Discussion Congenital retinal macrovessels are rare vascular anomalies, in which the diagnosis is usually incidental as their visual impact is minimal. In the rare cases where there is a significant visual impairment, this is due to macular hemorrhages, foveal cysts, serous macular detachment, or the course of the vessel itself through the foveal avascular zone.

Resumen Caso clinico Se presenta el caso de un varon de 35 anos sin antecedentes de interes que consulta por mala vision del ojo izquierdo objetivada de forma fortuita, en el cual tras un completo estudio se llega al diagnostico de macrovaso congenito retiniano con engrosamiento macular. Discusion Los macrovasos congenitos retinianos son una rara anomalia vascular cuyo diagnostico suele ser casual ya que la repercusion visual es minima. En los pocos casos en que se produce afectacion visual importante, esta se debe a hemorragias maculares, quistes foveales, desprendimiento seroso macular o al propio transcurso del vaso por la zona avascular foveal.

To assess the effectiveness of the implementation of a protocol for glycaemic control in critical care, in terms of maintenance of a pre-established target of blood glucose level, reduction of hyperglycaemia and prevention of severe hypoglycaemia.Prospective "pre-post" quasi-experimental study carried out in a general critical care unit. Adult patients treated with intravenous insulin were included. We recorded all glycaemic tests performed from November 2014 to August 2015 (pre-intervention) and from November 2015 to August 2016 (post-intervention). The intervention consisted of the implementation of an evidence-based glycaemic control protocol to achieve glycaemic levels in a range of 140-180mg/dl. Main variables analysed were: proportion of glycaemic tests in the target range, proportions of severe hypoglycaemia (under 40mg/dl) and hyperglycaemia over 200mg/dl.We analysed 7864 glycaemic tests from 125 patients, 66 pre-intervention and 59 post-intervention. Average age was 66.24±13.99 years, 64% of patients were male. The proportion of tests within the target range was higher in the intervention group (38.82 vs. 44.34 p.001). Only one case of severe hypoglycaemia was identified, which happened in the pre-intervention period. The rate of severe hyperglycaemia was lower in the post-intervention group (19.19 vs. 16.28 p=.001).Our experience shows that implementation of evidence-based interventions can improve glycaemic control during critical illness. We found higher glycaemia levels in the target range. The protocol proved useful in the prevention of severe hypoglycaemia. Nurse-led interventions based on clinical data improved health results in our patients.

Derivation and characterisation of endothelial cells from patients with chronic thromboembolic pulmonary hypertension The material obtained from pulmonary endarterectomy (PEA) offers the unique opportunity to study the pathophysiological mechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) at disease site. Metabolic changes and mitochondrial disarrangements in endothelial cells might elucidate a hyperproliferative apoptosis-resistant phenotype that could explain vascular changes occurring in CTEPH. The objective of our study was to develop an in vitro model of CTEPH using patient derived cell lines and assay endothelial cell metabolism, apoptosis and potential mitochondrial disturbances. Isolated cells obtained from freshly obstructive thromboembolic material collected at PEA (N=10), were confirmed as being endothelial cells based on cobblestone morphology, endothelial phenotype (flow cytometry, RT-PCR and immunofluorescence). Cell growth kinetics were evaluated using fold expansion, MTT assay, number of Ki67+ cells. We also measured: i) hypoxia-inducible factor 1-alpha (HIF-1a) expression by RT-PCR, ii) glycolytic enzymes and metabolites by colorimetric assays (such as lactate dehydrogenase (LDH) and lactate). iii) mitochondrial membrane potential (MMP), mitochondrial content and apoptosis/necrosis by flow cytometry and iv) mitochondrial dynamics (MD) by confocal microscopy. Isolated cells maintained cobblestone morphology and stained positive for endothelial markers (such as CD31, VE-cadherin, eNOS and vWF (von Willebrand Factor)). They showed a hyperproliferative phenotype when compared with control human pulmonary artery endothelial cell lines (HPAE): number of Ki67+cells (50.33±13.4 vs 32.5±9.5; p We concluded that endothelial cells obtained from PEA in CTEPH show a hyperproliferative phenotype, metabolic disturbance, impaired function and mitochondrial material dysfunction that may play a role in the pathogenesis of pulmonary hypertension.

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons.METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases.RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage.CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Introduction The two mechanisms postulated for cancer recurrence at the anastomosis site (‘anastomotic recurrence’ (AR)) after curative surgery for colorectal cancer are: (i) intraluminal dissemination of viable cancer cells; (ii) metachronous carcinogenesis related with changes in the local milieu provoked by the materials employed to carry out the anastomosis. Case History We describe a 79-year-old female who underwent a left hemicolectomy due to a stenotic lesion shown on colonoscopy: an adenocarcinoma (pT3NO, G2). One year after surgery, control colonoscopy revealed an AR, so a new resection was carried out. Pathology showed it to be a recurrent adenocarcinoma over the staple line (pT3N0, G2). One year after the second surgical procedure, control colonoscopy evinced a new AR, resulting in a new resection. Pathology revealed a new AR. Conclusions This is only the second time that a second isolated AR after curative resection for colorectal cancer has been reported.

Plastic materials have been worldwide applied in agriculture for soil mulching, greenhouse covering, irrigation and drainage pipes, bags, containers, pots, and agrochemical containers. All of these plastic materials require, at the end of their lifetime, suitable collection and treatment systems. Agricultural activities in some areas of the Apulia Region, Southern Italy, are characterized by huge quantities of plastic wastes and local authorities and farmers associations have been interested in solving this problem by applying modern land management tools such as Geographical Information System (G.I.S.). In this paper a G.I.S. methodology is applied to an area of 10,200 ha in the Trani municipality, included in the Province of Barletta, Andria, Trani (BAT) - Apulia Region, in order to assess the agricultural plastic waste generation. The use of plastics at the agricultural farms has been investigated and related to the land use by applying statistical analysis, orthophoto analysis and remote sensing surveys. These data were introduced in a specific geo-database, and the agricultural plastic waste quantity and localization were defined. Vineyards and olive groves are scattered in this area, so the agricultural plastic waste mostly consists in irrigation pipes, after-use covering films and anti-hail nets used on vineyards. The analysis carried out showed that up to 614 kg ha-1 of covering films waste are yearly produced in some areas while the estimation of waste from the anti-hail nets was up to 159 kg ha-1 and the waste yearly produced from irrigation pipes was up to 83 kg ha-1. Through the use of the G.I.S., the areas with high density of plastic wastes were pointed out thus allowing to determine the suitable location of temporary storage areas and collecting points, in order to optimize the transport of agricultural plastic waste from the farms to the collecting points and to the recycling firms.

Monitoring and controlling environmental parameters inside a greenhouse are required to reach high yields and low environmental impacts. Ventilation, shading, evaporative cooling and refrigeration are methods of controlling air temperature and relative humidity in Mediterranean greenhouses. Nevertheless ventilation and shading are often not sufficient to remove the excess heat, refrigeration is generally expensive and evaporative cooling is based on the exploitation of high quality water, a resource to be preserved in the Mediterranean areas. In order to enhance the sustainability levels of the greenhouse sector, renewable energy sources can be exploited with the application of solar absorption systems for greenhouse cooling in areas with high outdoor temperatures. These systems take advantage of the simultaneity between the solar energy availability and the greenhouse cooling demand allowing the reduction of conventional electricity. This paper presents the simulation and optimization of a solar cooling system designed for a Mediterranean greenhouse, having a surface of 300 m2, using 68 m2 of evacuated tube solar collectors, a LiBr absorption unit with a cooling capacity of 17.6 kW and a pilot distribution system providing the cooling power for the volume surrounding the crop. The simulation study, predicting the performance of the unit, was based on the experimental data collected at the experimental centre of the University of Bari, Southern Italy. The results of the simulation indicated that the system is seasonally in phase with the climatic data; the delivered yearly cooling capacity for the greenhouse was 113 GJ, the required solar energy 157 GJ and the available solar energy on the 68 m2 capturing surface, with a slope of 30°, was 265 GJ. The simulation can be used as a forecasting tool of the effects of the changes on the parameters of the system before applying them on the greenhouse system. © 2017 ISHS.

Stereotactic body radiation therapy (SBRT) developed as a result of technological advances in image-guided radiotherapy (IGRT), treatment planning, body stereotaxis, and motion management allows precise delivery of biologically potent dose to the tumor targets. Preclinical and clinical studies of SBRT have now demonstrated very promising results without significant toxicity in the treatment of primary and metastatic renal cell carcinoma (RCC) lesions. The additional benefit of SBRT may be the abscopal (distant bystander) effect, mediated by an immunological response. In addition, high single-dose radiation such as SBRT may overcome radioresistance of RCC caused by the von Hippel-Lindau (VHL) tumor-suppressor gene mutation and hypoxia-inducible factor-1 (HIF-1). As radiotherapy is not considered as a definitive treatment of RCC, a combination of radiotherapy and various systemic therapies has not been examined. However, SBRT could change the role of radiotherapy for RCC, and the development of combination therapy needs to be explored in the future trials. This review focused on the role of SBRT in the treatment of primary and metastatic RCC.

Aim The diagnostic accuracy of the faecal immunochemical test (FIT) at a 100 ng/ml threshold for colorectal cancer (CRC) was compared with National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN) referral criteria. Method A multicentre, prospective, blind study of diagnostic tests was carried out in two Spanish health areas. In 787 symptomatic patients referred for a diagnostic colonoscopy, we determined whether patients met NICE and SIGN referral criteria. All patients performed one FIT determination (OCsensor™). The sensitivity and specificity for CRC detection were determined with McNemar's test. The diagnostic odds ratio as well as the number needed to scope (NNS) to detect a CRC were calculated. Results We detected CRC in 97 (12.3%) patients; 241 (30.6%) had an FIT ≥ 100 ng/ml and 300 (38.1%) and 473 (60.1%) met NICE and SIGN referral criteria. The FIT had a higher sensitivity for CRC detection than NICE criteria (87.6%, 61.9%; P

Resumen Objetivo La biopsia selectiva del ganglio centinela (BSGC) como procedimiento de estadificacion en el cancer de mama multiple es cuestion de controversia. Nuestro objetivo es evaluar la eficiencia de deteccion del ganglio centinela (GC) en las pacientes con cancer multifocal o multicentrico, y la seguridad de su aplicacion clinica, tras un seguimiento prolongado. Material y metodos Se realiza un estudio prospectivo descriptivo. Se estudian 89 pacientes con cancer multiple de mama sometidas a BSGC (73 procesos multifocales, 16 multicentricos), comparandolas con las que presentaron neoplasia unifocal. En la mayor parte de las BSGC se realizo administracion periareolar del radiocoloide. Se realiza la evaluacion a los 67,2 meses de seguimiento medio (32-126 meses). Resultados Las tasas de localizacion gammagrafica y quirurgica del GC en las pacientes con cancer de mama multiple fueron respectivamente 95,5% y 92,1%, observandose mayor porcentaje de GC extraaxilares que en los procesos unifocales (11,7% frente a 5,4%) y un numero de GC por paciente significativamente mayor (1,70 frente a 1,38). La tasa de localizacion del GC en el cancer multicentrico fue ligeramente inferior al multifocal (87,5% frente a 93,1%) y el hallazgo de drenajes extra-axilares mas elevado (20% frente a 10%). El numero promedio de GC por paciente fue significativamente superior en el cancer multicentrico (2,33 frente a 1,57). No se han registrado recurrencias axilares en el seguimiento de las pacientes con cancer multiple. Conclusiones La BSGC mediante inyeccion periareolar es un procedimiento preciso y fiable de estadificacion del cancer de mama multiple, incluso multicentrico.

Objective Sentinel lymph node biopsy (SLNB) as a staging procedure in multiple breast cancer is a controversial issue. We have aimed to evaluate the efficacy of sentinel node (SN) detection in patients with multifocal or multicentric breast cancer as well as the safety of its clinical application after a long follow-up. Material and methods A prospective descriptive study was performed. Eighty-nine patients diagnosed of multiple breast cancer (73 multifocal; 16 multicentric) underwent SLNB. These patients were compared to those with unifocal neoplasia. Periareolar radiocolloid administration was performed in most of the patients. Evaluation was made at an average of 67.2 months of follow-up (32–126 months). Results Scintigraphic and surgical SN localization in patients with multiple breast cancer were 95.5% and 92.1%, respectively. A higher percentage of extra-axillary nodes were observed than in the unifocal group (11.7% vs. 5.4%) as well as a significantly higher number of SN per patient (1.70 vs. 1.38). The rate of SN localization in multicentric cancer was slightly lower than in multifocal cancer (87.5% vs. 93.1%), and the finding of extra-axillary drainages was higher (20% vs. 10%). Number of SN per patient was significantly higher in multicentric breast cancer (2.33 vs. 1.57). No axillary relapses have been demonstrated in the follow-up in multiple breast cancer patients group. Conclusions SLNB performed by periareolar injection is a reliable and accurate staging procedure of patients with multiple breast cancer, including those with multicentric processes.

Objectives To analyze trends in cytogenetic prenatal diagnosis in Cuba and to analyze possible causes leading to a low Down syndrome prevalence in a country where the triple test is not available. Methods An analysis of the Cuban program in prenatal cytogenetic diagnosis from 1984 to 2012 was conducted. Results are described, with particular emphasis on indications, abnormal results, types of invasive procedures, and terminations of pregnancy. Results Cytogenetic prenatal diagnostic analyses (n=75095) were conducted; maternal age was the indication for 77.9% of the amniocenteses and chorionic villus samplings. The detection rate of chromosomally abnormal pregnancies was 2.3% for maternal age and increased to 8–9% for other indications. When a chromosomal abnormality was identified, 88.5% terminated the pregnancy. In 2002, the live birth prevalence of Down syndrome was 8.4 per 10000 live births, and in 2012, 7 per 10000. Conclusion Prenatal diagnosis in Cuba has contributed to a significant reduction in chromosomal aberrations. The impact increased because of the demographic trends of the population, the high index of terminations of pregnancy, and the establishment of a network of cytogenetic laboratories throughout Cuba. © 2014 John Wiley & Sons, Ltd.

Introduction La neurofibromatose 1 (NF1) a un phenotype variable associe a un fardeau medical et social majeur, notamment par les neurofibromes cutanes (NFcut). Leurs traitements actuels sont la chirurgie et le laser. Il est envisage de nouvelles options therapeutiques par voie locale ou systemique. L’objectif de notre etude etait de recueillir l’opinion de patients sur leur fardeau, leur prise en charge actuelle et leurs attentes/preferences therapeutiques. Materiel et methodes Population : une communaute de patients anonymes (France, Grande Bretagne, Espagne et Allemagne), atteints de NF1 avec des NFcut a ete constituee par l’intermediaire des associations et des reseaux sociaux grâce a une plateforme en ligne (Carenity). Les patients declaraient leur profil sociodemographique et auto-evaluaient la severite de leurs NFcut par comparaison avec des images. Questionnaire : un forum anime sur cette plateforme permettait de recueillir un verbatim sur les NFcut et de constituer un questionnaire sur le fardeau des NFcut, la satisfaction sur leur prise en charge actuelle et leurs attentes vis a vis de futurs traitements. Ce questionnaire a ete valide par deux experts et administre en ligne. Analyses : seuls les questionnaires complets ont ete analyses en correspondances multiples. Resultats Patients : 219 questionnaires etaient remplis, 49 exclus ne remplissant pas les criteres d’inclusion/qualite. Pour les 170 (110 femmes) patients retenus (France [n = 75], Espagne [n = 32], GB [n = 30], Allemagne [n = 33]) l’âge moyen etait de 37 ans (18–79). Quarante-neuf pour cent declaraient entre 11 et 50 NFcut, 37 % plus de 50. Cinquante-quatre pour cent avaient plus de 10 NFcut sur les zones visibles. Classement par fardeau : inesthetique/visibilite > evolution possible > douleurs/prurit. Prise en charge des NFcut : 65 % chirurgie, 37 %, laser, 26 % les deux. L’indice de satisfaction etait de 7/10 pour le laser et de 8/10 pour la chirurgie. Soixante-quinze pour cent des patients declaraient de nouveaux NFcut apres la procedure. Soixante pour cent des patients seraient prets pour un traitement a vie topique ou systemique quotidien. L’attente mise en priorite est le blocage de la croissance des NFcut (62 %) puis la reduction du nombre (44 %). Soixante-dix pour cent seraient satisfaits si 30 % de leurs NFcut disparaissaient. Soixante-trois pour cent etaient prets a attendre 6 mois pour voir les premiers resultats. Deux tiers des patients privilegiaient la tolerance a l’efficacite. Discussion Notre etude d’opinion confirme le fardeau lie aux NFcut, la crainte liee a l’evolution et la chirurgie et le laser comme traitements actuels de reference. Les patients ont des attentes raisonnables vis a vis de futurs nouveaux traitements : prise a vie, efficacite lente et modeste, privilegiant la securite sur l’efficacite. Conclusion Cette enquete devra etre prise en compte dans l’elaboration des schemas therapeutiques et la comparaison des nouveaux traitements devra se faire avec les techniques existantes.

Placenta percreta is a sub-type of placenta accreta in which this organ invades the whole uterine wall and affects the adjacent organs. It is a condition with a high surgical risk which generally requires an obstetric hysterectomy. We present the case of a 36 year-old pregnant woman diagnosed with placenta percreta with bladder and intestinal invasion. She suffered a hypovolaemic shock during surgery which required a massive transfusion of blood products and inotropic support. Three further successive surgeries were required due to the bleeding, with selective embolisation of the hypogastric arteries being performed in one of them. She required 13 days in intensive care. The total volume of blood products transfused was, 43 units of red cells, 28 units of plasma, and 8 platelet pools. The importance of early prenatal diagnosis is emphasised in order to adequately plan the operation, and should include a multidisciplinary team (general surgeons, urologists, vascular surgeons), as well as experienced anaesthesiologists and obstetricians.

Objectives To evaluate biochemical non-evidence of disease and adverse events of salvage intensity-modulated radiotherapy using an endorectal balloon for prostate cancer patients after radical prostatectomy. Methods Data of 107 patients (median age 65 years) with persistent (>0.1 ng/mL) or rising prostate-specific antigen after radical prostatectomy were retrospectively analyzed. The mean dose to clinical target volume was 70 Gy in 32 fractions (the equivalent dose in 2 Gy fraction is 73.2 Gy based on α:β = 2). Biochemical non-evidence of disease and predictive factors were assessed. Genitourinary toxicity and gastrointestinal toxicity were also evaluated using the Radiation Therapy Oncology Group toxicity criteria. Results The median follow up was 37 months (range 6–126 months). A total of 48 patients developed biochemical recurrence. The 3- and 5-year biochemical non-evidence of disease rates of all patients were 52.6% and 48.8%, respectively. The Gleason score (≥4 + 3, ≤3 + 4) and pre-intensity-modulated radiotherapy prostate-specific antigen level (≥0.5 ng/mL

Understanding enzymatic reactions with atomic resolution has proven in recent years to be of tremendous interest for biochemical research, and thus, the use of QM/MM methods for the study of reaction mechanisms is experiencing a continuous growth. Glycosyltransferases (GTs) catalyze the formation of glycosidic bonds, and are important for many biotechnological purposes, including drug targeting. Their reaction product may result with only one of the two possible stereochemical outcomes for the reacting anomeric center, and therefore, they are classified as either inverting or retaining GTs. While the inverting GT reaction mechanism has been widely studied, the retaining GT mechanism has always been controversial and several questions remain open to this day. In this work, we take advantage of our recent GPU implementation of a pure QM(DFT-PBE)/MM approach to explore the reaction and inhibition mechanism of MshA, a key retaining GT responsible for the first step of mycothiol biosynthesis, a low weight thiol compound found in pathogens like Mycobacterium tuberculosis that is essential for its survival under oxidative stress conditions. Our results show that the reaction proceeds via a front-side SNi-like concerted reaction mechanism (DNAN in IUPAC nomenclature) and has a 17.5 kcal/mol free energy barrier, which is in remarkable agreement with experimental data. Detailed analysis shows that the key reaction step is the diphosphate leaving group dissociation, leading to an oxocarbenium-ion-like transition state. In contrast, fluorinated substrate analogues increase the reaction barrier significantly, rendering the enzyme effectively inactive. Detailed analysis of the electronic structure along the reaction suggests that this particular inhibition mechanism is associated with fluorine´s high electronegative nature, which hinders phosphate release and proper stabilization of the transition state. Fil: Blanco Capurro, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Hopkins, Chad W.. University of Florida; Estados Unidos Fil: Pierdominici Sottile, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina Fil: González Lebrero, Mariano Camilo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina Fil: Roitberg, Adrián. University of Florida; Estados Unidos Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina

Introduction Stage classification provides a consistent language to describe the anatomic extent of disease and is therefore a critical tool in caring for patients. The Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer developed proposals for revision of the classification of lung cancer for the eighth edition of the tumor, node, and metastasis (TNM) classification, which takes effect in 2017. Methods An international database of 94,708 patients with lung cancer diagnosed in 1999–2010 was assembled. This article describes the process and statistical methods used to refine the lung cancer stage classification. Results Extensive analysis allowed definition of tumor, node, and metastasis categories and stage groupings that demonstrated consistent discrimination overall and within multiple different patient cohorts (e.g., clinical or pathologic stage, R0 or R-any resection status, geographic region). Additional analyses provided evidence of applicability over time, across a spectrum of geographic regions, histologic types, evaluative approaches, and follow-up intervals. Conclusions An extensive analysis has produced stage classification proposals for lung cancer with a robust degree of discriminatory consistency and general applicability. Nevertheless, external validation is encouraged to identify areas of strength and weakness; a sound validation should have discriminatory ability and be based on an independent data set of adequate size and sufficient follow-up with enough patients for each subgroup.

The lymphatic vasculature provides a route for cancer metastases, and its dysfunction after cancer treatment can result in lymphedema. However, changes in the lymphatics before, during, and after surgery and radiation remain unclear.Near-infrared fluorescence lymphatic imaging was performed before and after lymph node dissection and fractionated radiotherapy to assess changes in external lymphatic function.Patients who underwent both lymph node dissection and radiotherapy developed lymphatic dermal backflow on treated sides ranging from days after the start of radiotherapy to weeks after its completion, whereas contralateral regions that were not associated with lymph node dissection but also treated with radiotherapy experienced no such changes in external lymphatic anatomies.The external lymphatics undergo transient changes during and weeks after lymph node dissection and radiotherapy. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1177-1188, 2017.

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward.In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate-OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono-to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process. Fil: Gauto, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina Fil: Petruk, Ariel Alcides. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Modenutti, Carlos Pablo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Blanco Capurro, Juan Ignacio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Di Lella, Santiago. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina

Renal cell carcinoma (RCC) metastases have been reported in almost every organ. The most common involved organs are the lungs, liver, kidneys, bones, and brain.1,2 Autopsy series have reported RCC adrenal metastases rates ranging from 7% to 19%.2-4 Contralateral adrenal involvement is rare. In one study the incidence was 2.5%.5 In addition contralateral adrenal metastases from RCC can present late, even after 23 years from primary tumor resection.4,6 Such unusual delay in presentation, infrequent occurrence, and confusing clinical presentation can lead to misdiagnosis, delayed diagnosis, or failure to treat promptly.3 Herein a case of RCC involving the contralateral adrenal gland that was successfully treated with SBRT is reported. The patient had right nephrectomy and right adrenalectomy 12 years earlier. His resulting adrenal

Owing to the liver’s integral role in biosynthesis and homeostasis, management of primary and secondary malignancies arising in this organ is of paramount oncologic significance. Over the past several decades, substantial progress has been achieved in the imaging and treatment of early and advanced hepatic malignancies. Radiation therapy (RT) has recently emerged as one of many local therapeutic options for both primary and metastatic liver cancer. Recent phase I and II studies describe promising efficacy and side effect profile; however, phase III studies are needed to establish RT among standard of care therapeutic modalities. In this review, we will describe (a) the scope, epidemiology, and standard treatment options for liver cancer; (b) relevant diagnostic imaging techniques; and (c) provide an in-depth review of RT treatment techniques, dose–volume limits of normal tissues, and results of both conventional and hypofractionated RT liver trials pertaining to primary and secondary liver cancers with emphasis on three-dimensional conformal radiation therapy (3DCRT) and stereotactic body radiotherapy (SBRT) studies.

Resumen Introduccion Comparar la eficacia de un regimen analgesico multimodal con 2 tecnicas diferentes (bloqueo del nervio femoral con dosis unica y bloqueo continuo del nervio femoral) en el control del dolor, consumo de opioides y efectos secundarios en pacientes intervenidos de artroplastia total de rodilla. Material y metodos Estudio prospectivo aleatorizado, de pacientes intervenidos de protesis de rodilla con anestesia subaracnoidea. La analgesia postoperatoria consistio en tramadol, dexketoprofeno y paracetamol, y una de las 2 tecnicas siguientes: bloqueo del nervio femoral con dosis unica de 30 ml de ropivacaina 0,5% o la anterior dosis mas perfusion continua por un cateter femoral de ropivacaina 0,375%, 6 ml/h durante 48 h. Se registraron las variables demograficas, anestesicas y quirurgicas, intensidad del dolor segun escala visual analogica, consumo de opiaceos y complicaciones a las 24 y 48 h. Resultados Se incluyeo a 104 pacientes. No hubo diferencias demograficas entre los grupos. La intensidad del dolor fue menor en el grupo en el que se realizo bloqueo femoral continuo, especialmente a las 48 h, frente al bloqueo con dosis unica, con menor consumo de analgesia de rescate en el bloqueo femoral continuo. La incidencia de efectos secundarios fue similar, observandose un menor bloqueo sensitivo de larga duracion en el bloqueo femoral con dosis unica. Conclusiones El uso de los bloqueos nerviosos perifericos esta aceptado para la analgesia postoperatoria de las artroplastias de las rodillas. El bloqueo femoral continuo es una alternativa valida disminuyendo el consumo de opiaceos de rescate y la intensidad del dolor (especialmente a las 48 h) respecto al bloqueo femoral aislado.

To investigate the utility of stereotactic body radiotherapy (SBRT) in the treatment of painful renal cell carcinoma (RCC) bone metastases, and for a possible dose effect on time to symptom relief.Eighteen patients with 24 painful osseous lesions from metastatic RCC were treated with SBRT. The most common treatment regimens were 24 Gy in 3 fractions and 40 Gy in 5 fractions. The times from treatment to first reported pain relief and time to symptom recurrence were evaluated. Median follow-up was 38 weeks (1-156 weeks).Seventy-eight percent of all patients had pain relief. Patients treated with a BED85 Gy achieved faster and more durable pain relief compared to those treated with a BED85 Gy. There was decrease in time to pain relief after a change in treatment regimen to 8 Gy × 5 fractions (BED = 86). There was only one patient with grade 1 skin toxicity. No neurological or other toxicity was observed.SBRT can safely and effectively treat painful RCC bony metastases. There appears to be a relationship between radiation dose and time to stable pain relief.

Renal cell carcinoma (RCC) is traditionally considered to be radioresistant; therefore, conventional radiotherapy (RT) fraction sizes of 1.8 to 2 Gy are thought to have little role in the management of primary RCC, especially for curative disease. In the setting of metastatic RCC, conventionally fractionated RT has been an effective palliative treatment in 50% of patients. Recent technological advances in radiation oncology have led to the clinical implementation of image-guided radiotherapy, allowing biologically potent doses to the tumors intra- and extra-cranially. As predicted by radiobiologic modeling, favorable outcomes have been observed with highly hypofractionated schemes modeled after the experience with intracranial stereotactic radiosurgery (SRS) for RCC brain metastases with reported local control rates averaging 85%. At present, both primary and metastatic RCC tumors may be successfully treated using stereotactic approaches, which utilize steep dose gradients to maximally preserve function and avoid toxicity of adjacent organs including liver, uninvolved kidney, bowel, and spinal cord regions. Future endeavors will combine stereotactic body radiation therapy (SBRT) with novel targeted therapies, such as tyrosine kinase inhibitors and targeted rapamycin (mTOR) inhibitors, to maximize both local and systemic control.

Stereotactic body radiation therapy (SBRT) is a promising treatment option for prostate cancer. Hypofractionation regimens, such as SBRT, may be more advantageous compared with conventional regimens because low α:β ratio of prostate cancer has high sensitivity to dose per fraction. In addition, a smaller and tighter margin with SBRT is expected to provide a low toxicity rate without reducing tumor control. The purpose of this article is to examine radiobiological, technical and clinical aspects of SBRT for prostate cancer.

Aim: The aim of this study was to establish the efficacy and safety of sentinel lymph node biopsy for lymph node staging in patients with breast cancer and prior breast surgery, considering its extension, localization and time since the previous surgical procedure. Material and methods: A sentinel lymph node biopsy was performed in 38 patients with early breast cancer and previous breast surgery: recent excisional biopsy in 22 patients (Group I), previous lumpectomy or mammoplasty in 16, including one case of cancer treated with breast-conserving surgery (tumor recurrence). Lymphoscintigraphy was performed after periareolar injection, also sometimes adding an injection near to the surgical scar. After removing the sentinel node, axillary lymph node dissection was performed when the lymph node was positive (and not localized). Results: The efficacy of the scintigraphic localization of the sentinel node was 92.1% of the patients, with 15.8% of extra-axillary drainages. Axillary intraoperative detection was 81.6%. The identification rate after recent excisional biopsy or previous surgery was similar (81.8 vs 81.2%). However, extra-axillary sentinel nodes were more frequent in Group II (9.1 vs 25%). Having a localization of previous surgical procedures in upper outer quadrant caused drainages outside of the axilla more frequently (27.2 vs 11.1%). Axillary detection rate was similar to other quadrants (81.8 vs 81.5%). The rate of breast cancer-related events was 5.2% (2/38), without axillary recurrences (mean follow-up: 3 years). Conclusion: Sentinel lymph node biopsy in patients with previous but not extensive breast surgery is safe. Extra-axillary drainages are more common when the previous surgical area was wide, especially in the upper-outer quadrant.

Aim The aim of this study was to establish the efficacy and safety of sentinel lymph node biopsy for lymph node staging in patients with breast cancer and prior breast surgery, considering its extension, localization and time since the previous surgical procedure. Materials and methods A sentinel lymph node biopsy was performed in 38 patients with early breast cancer and previous breast surgery: recent excisional biopsy in 22 patients (Group I), previous lumpectomy or mammoplasty in 16, including one case of cancer treated with breast-conserving surgery (tumor recurrence). Lymphoscintigraphy was performed after periareolar injection, also sometimes adding an injection near to the surgical scar. After removing the sentinel node, axillary lymph node dissection was performed when the lymph node was positive (and not localized). Results The efficacy of the scintigraphic localization of the sentinel node was 92.1% of the patients, with 15.8% of extra-axillary drainages. Axillary intraoperative detection was 81.6%. The identification rate after recent excisional biopsy or previous surgery was similar (81.8 vs 81.2%). However, extra-axillary sentinel nodes were more frequent in Group II (9.1 vs 25%). Having a localization of previous surgical procedures in upper outer quadrant caused drainages outside of the axilla more frequently (27.2 vs 11.1%). Axillary detection rate was similar to other quadrants (81.8 vs 81.5%). The rate of breast cancer-related events was 5.2% (2/38), without axillary recurrences (mean follow-up: 3 years). Conclusion Sentinel lymph node biopsy in patients with previous but not extensive breast surgery is safe. Extra-axillary drainages are more common when the previous surgical area was wide, especially in the upper-outer quadrant.

Our aim was to assess the suitability of ultra-high performance liquid chromatography (UHPLC) for the simultaneous determination of biomarkers of vitamins A (retinol, retinyl esters), E (alpha- and gamma-tocopherol), D (25-OH-vitamin D), and the major carotenoids in human serum to be used in clinical practice. UHPLC analysis was performed on HSS T3 column (2.1 x 100 mm; 1.8 microm) using gradient elution and UV-VIS detection. The system allows the simultaneous determination of retinol, retinyl palmitate, 25-OH-vitamin D, alpha- and gamma-tocopherol, lutein plus zeaxanthin, alpha-carotene, beta-carotene, alpha- and beta-cryptoxanthin and lycopene. The method showed a good linearity over the physiological range with an adequate accuracy in samples from quality control programs. Suitability of the method in clinical practice was tested by analyzing samples (n = 286) from patients. In conclusion, UHPLC constitutes a reliable approach for nutrient/biomarker profiling allowing the rapid, simultaneous and low-cost determination of vitamins A, E, and D (including vitamers and ester forms) and the major carotenoids in clinical practice.

Objective : The aim of the present research was to evaluate, in an open, short-term study, the efficacy and tolerability of a probiotic containing Lactobacillus paracasei subsp. paracasei F19 in irritable bowel syndrome (IBS). Patients and methods : Studies were carried out on 100 patients with IBS (38 male, 62 female, age range 18-68 years), 52 with diarrhoea and 48 with constipation, recruited in accordance with the Rome II diagnostic criteria. All patients were administered Genefilus F19 (Siffra Pharmaceuticals SpA, Florence, Italy), a commercial preparation containing L. paracasei subsp. paracasei F19, at a dose of one sachet (dissolved in water) twice daily for 14 days. Each sachet contained 12x10 ? genetically stable microorganisms of L . paracasei subsp. paracasei F19, combined with 750 mg gluco-oligosaccharides plus vitamins B1, B5 and B6. Symptoms were evaluated, based upon a daily diary, before and after treatment. In addition, in a series of 20 consecutive patients, L. paracasei subsp. paracasei F19 content was evaluated in faeces before and after treatment. Results: Following treatment, abdominal pain was no longer present in 94% of the patients with IBS with diarrhoea or in 87% of those with IBS with constipation. Diarrhoea was no longer present in 88% of the patients, while constipation was no longer present in 83% of the patients. Abdominal distension had disappeared, or considerably improved, in 95% of the study population. These percentages remained practically unchanged at follow-up, 2 weeks after the end of treatment. Tolerability was excellent no significant side effects or drop-outs were recorded. The results of microbiological evaluations performed on faeces revealed a low microbial L. paracasei subsp. paracasei F19 load before treatment and a marked increase in load following treatment, with a minimum of 2, to a maximum of 10, cfu/g faeces. Conclusions : In this short-term study, Genefilus F19 was confirmed to be efficacious and well tolerated in patients with IBS presenting with diarrhoea or with constipation and, therefore, useful in everyday clinical practice. Double-blind controlled studies, with placebo, including clinical evaluations at medium- and longterm follow-up, are now under way with a larger series of patients to confirm these promising findings. Key words: L. paracasei subsp. paracasei F19, irritable bowel syndrome, constipation, diarrhoea

A new jadeitite jade locality has been discovered in the serpentinite-matrix subduction melange of the Sierra del Convento (eastern Cuba) in a context associated with tectonic blocks of garnet-epidote amphibolite, tonalitic–trondhjemitic epidote gneiss, and blueschist. The mineral assemblages of jadeitite jade and jadeite rocks are varied and include combinations of jadeite, omphacite, albite, paragonite, analcime, clinozoisite-epidote, apatite, phlogopite, phengite, chlorite, glaucophane, titanite, rutile, zircon, and quartz formed during various stages in their P–T evolution. Field relationships are obscure, but some samples made almost exclusively of jadeite show evidence of crystallization from fluid in veins. In one of these samples studied in detail jadeite shows complex textural and chemical characteristics (including oscillatory zoning) that denote growth in a changing chemical medium. It is proposed that interaction of an Al–Na rich fluid with ultramafic rocks produced Al–Na–Mg–Ca fluids of varying composition. Episodic infiltration of these fluids, as a result of episodic opening of the veins, developed oscillatory zoning by direct precipitation from fluid and after reaction of fluid with pre-existing jadeite. The latest infiltrating fluids were richer in Mg–Ca, favouring the formation of omphacite and Mg–Ca rich jadeite in open voids and the replacement of earlier jadeite by fine-grained omphacite + jadeite at 550–560°C. This new occurrence of jadeite in Cuba opens important perspectives for archeological studies of pre-Columbian jade artifacts in the Caribbean region.