Improving the identification of the source of faecal pollution in water using a modelling approach: From multi-source to aged and diluted samples.

The last decades have seen the development of several source tracking (ST) markers to determine the source of pollution in water, but none of them show 100% specificity and sensitivity. Thus, a combination of several markers might provide a more accurate classification. In this study Ichnaea® software was improved to generate predictive models, taking into account ST marker decay rates and dilution factors to reflect the complexity of ecosystems. A total of 106 samples from 4 sources were collected in 5 European regions and 30 faecal indicators and ST markers were evaluated, including E. coli, enterococci, clostridia, bifidobacteria, somatic coliphages, host-specific bacteria, human viruses, host mitochondrial DNA, host-specific bacteriophages and artificial sweeteners. Models based on linear discriminant analysis (LDA) able to distinguish between human and non-human faecal pollution and identify faecal pollution of several origins were developed and tested with 36 additional laboratory-made samples. Almost all the ST markers showed the potential to correctly target their host in the 5 areas, although some were equivalent and redundant. The LDA-based models developed with fresh faecal samples were able to differentiate between human and non-human pollution with 98.1% accuracy in leave-one-out cross-validation (LOOCV) when using 2 molecular human ST markers (HF183 and HMBif), whereas 3 variables resulted in 100% correct classification. With 5 variables the model correctly classified all the fresh faecal samples from 4 different sources. Ichnaea® is a machine-learning software developed to improve the classification of the faecal pollution source in water, including in complex samples. In this project the models were developed using samples from a broad geographical area, but they can be tailored to determine the source of faecal pollution for any user.

High delayed mortality after the first episode of Clostridium difficile infection.

Clostridium difficile infection (CDI) is characterized by a high delayed and unrelated mortality. Predicting delayed mortality in CDI patients could allow the implementation of interventions that could reduce these events. A prospective multicentric study was carried out to investigate prognostic factors associated with mortality. It was based on a cohort (July 2015 to February 2016) of 295 patients presenting with CDI. Logistic regression was used and the model was calibrated using the Hosmer-Lemeshow test. The mortality rate at 75 days in our series was 18%. Age (>65 years), comorbidity (defined by heart failure, diabetes mellitus with any organ lesion, renal failure, active neoplasia or immunosuppression) and fecal incontinence at clinical presentation were associated with delayed (75-day) mortality. When present, each of the aforementioned variables added one point to the score. Mortalities with 0, 1, 2 and 3 points were 0%, 9.4%, 18.5% and 38.2%, respectively. The area under the ROC curve was 0.743, and the Hosmer-Lemeshow goodness-of-fit test p value was 0.875. Therefore, the prediction of high delayed mortality in CDI patients by our scoring system could promote measures for increasing survival in suitable cases.

A Novel GMPPA Mutation in Two Adult Sisters with Achalasia, Alacrima, Short Stature, Dysmorphism, and Intellectual Disability.

The alacrima, achalasia, and mental retardation syndrome (AAMR) is a newly described autosomal recessive disorder characterized by the onset of these 3 main features at birth or in early infancy. At present, only 16 cases have been reported. Recently, it was shown that AAMR is due to mutations in the guanosine diphosphate (GDP)-mannose pyrophosphorylase A (GMPPA) gene. These mutations induce a significant GDP-mannose overload, which may affect protein glycosylation. Herein, for the first time, we describe 2 adult sisters with AAMR with a previously not reported deleterious homozygous missense mutation c.1118G>C (p.Arg373Pro) in the GMPPA gene, born to healthy consanguineous heterozygous parents from an ancient endogamous population. The main symptoms in both sisters started soon after birth with achalasia and feeding difficulties, requiring surgical treatment. Both sisters showed alacrima identified during the first months of life, delayed psychomotor development, speech delay, facial dysmorphism, limb defects, short stature, and moderate intellectual disability. Alacrima and feeding difficulties due to achalasia during the neonatal period or first months of life, in the absence of adrenal cortical insufficiency, should spur to investigate AAMR by sequencing the GMPPA gene.

Using Genetic and Epigenetic Markers to Improve Differential Diagnosis of Prostate Cancer and Benign Prostatic Hyperplasia by Noninvasive Methods in Mexican Patients.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy in Mexican men. Serum prostate-specific antigen (PSA) is the usual noninvasive biomarker used for its detection. Its low specificity can increase the number of unnecessary prostate biopsies and the incidence of unpleasant complications for patients. The androgen-receptor gene (AR-CAG) repeat length and the percentage of promoter methylation (PPM) of genes glutathione-S-transferase P1 (GSTP1) and Ras association domain family 1 isoform A (RASSF1A) improve PCa detection. As an option for noninvasive assessment, we evaluated a combined analysis of all these biomarkers. PATIENTS AND METHODS: A total of 186 patients scheduled for biopsy were included in the present study. PSA and AR-CAG repeats were analyzed in blood samples. The PPM of GSTP1 and RASSF1A genes was estimated in prostate tissue and urinary sediment cells (USCs) and plasma DNA using quantitative methylation-specific polymerase chain reaction. The predictive values for PCa and benign prostatic hyperplasia (BPH), logistic regression analysis, receiver operating characteristic curve, and decision curve analysis were used to assess the differential diagnosis. RESULTS: Statistically significant differences between PCa and BPH patients were observed for all biomarkers, with higher positive and negative predictive values when all biomarkers were included in the analysis, attaining USC values of 89.2% and 78.0%, respectively. The differential diagnosis accuracy of PSA (area under the curve, 0.59) increased to 0.70 and 0.68, respectively, when the combined analysis of PPM of RASSF1Aplasma or GSTP1AUSC and AR-CAG repeats was performed. Decision curve analysis showed the utility of the combined analysis to decrease the number of unnecessary biopsies. CONCLUSION: The results showed that combined analysis of the proposed biomarkers in plasma and USCs significantly increased the confidence for the differential diagnosis for PCa and BPH. This noninvasive practice might help in the early detection of PCa and patient follow-up, avoiding to some extent unnecessary prostate biopsies.

Prediction of recurrent clostridium difficile infection at the bedside: the GEIH-CDI score.

Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at increased risk of recurrent CDI makes it possible to select candidates for treatment with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises four factors: age (70-79 years and ≥80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65-0.79). Application of the tool makes it possible to select patients at high risk (>50%) of recurrence and patients at low risk (<10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI.

Comparación de los Perfiles Farmacodinámicos de Tres Moléculas de Remifentanilo en cuanto a su Respuesta Hemodinámica a las Maniobras de Laringoscopia e Intubación Traqueal / Comparison of the pharmacodynamic profiles of three molecules of remifentanil in terms of hemodynamic response to laryngoscopy and tracheal intubation maneuvers

Introduction: Several remifentanil products are commercialized in Colombia though they have never been compared in a clinical setting. Objective: The aim of this study was to investigate the pharmacodynamic profile of the branded remifentanil molecule (group O: Glaxo SmithKline Manufacturing S.P.A.) and two unbranded molecules (group A: Laboratorios Chalver de Colombia S.A. and group B: Instituto Biológico Contemporáneo, Argentina) registered in Colombia. Methods: We carried out a double-blind, randomized, controlled trial. The branded molecule of remifentanil (group O, n = 29) was compared with the two unbranded molecules (group A, n = 29; group B, n = 32) during anesthetic induction and tracheal intubation in adult patients ASA I without predictors for difficult airway. The target controlled infusion (TCI) doses evaluated were 6, 8 and 10ng/ml with the Minto model. Induction was complemented with propofol 5 mcg/ml (TCI) with the Schneider model and rocuronium 0.6 mg/kg. The primary outcome was the difference between preintubation (TCI equilirium) and postintubation (maximum measurement within 5 min) mean arterial pressure and heart rate. Results: A similar pharmacodynamic profile was observed in all of the studied remifentanil molecules. The differences in the change in heart rate were 1.27 (95% CI -3.11;5.67) with molecule A and 1.40 (95% CI -2.65;5.46) with molecule B compared to molecule O (beats/min). The differences in the change in mean arterial pressure were 1 (95% CI -4.81;6.81) with molecule A and 1.82 (95% CI -4.08;7.74) with molecule B compared to molecule O (mmHg). There was one case of arterial hypotension in each group. Conclusion: The results suggest that, from a pharmacodynamic point of view, branded and unbranded remifentanil molecules are similar for laryngoscopy/intubation with TCI doses 6, 8 and 10ng/ml.

Introducción: En Colombia se comercializan diferentes moléculas de Remifentanil que nunca han sido comparadas en un entorno clínico. Objetivo: El objetivo de este estudio fue investigar el perfil farmacodinámico de la molécula innovadora de Remifentanil (grupo O: Glaxo SmithKline Manufacturing S.P.A.) y dos moléculas genéricas (grupo A: Laboratorios Chalver de Colombia S.A. y grupo B: Instituto Biológico Contemporáneo, Argentina) registradas en Colombia. Métodos: Se llevó a cabo un experimento clínico doble ciego, aleatorizado, controlado. Se comparó la molécula original de Remifentanil (grupo O, n = 29) frente a las dos moléculas genéricas (grupo A, n = 29; grupo B, n = 32) durante la inducción anestésica e intubación oro-traqueal de pacientes adultos ASA I sin predictores de vía aérea difícil. Se evaluaron las dosis 6, 8 y 10 ng/ml (TCI, Target Controlled Infusion) con el modelo de Minto. La inducción se complementó con Propofol 5 mcg/ml (TCI) con modelo de Schneider y Rocuronio 0.6mg/kg. El desenlace primario se evaluó como las diferencias en la presión arterial media y en la frecuencia cardiaca preintubación (momento en que se alcanza la concentración objetivo en sitio efecto) y posintubación (máximo valor alcanzado en 5 minutos). Resultados: Se observó similitud en el perfil farmacodinámico de las moléculas de Remifentanil estudiadas. Las diferencias en el cambio de frecuencia cardiaca fue de 1.27 (IC 95% -3.11;5.67) con la molécula A y 1.40 (IC 95% -2.65;5.46) con la molécula B frente a la molécula O (latidos/minuto). Las diferencias en el cambio de presión arterial media fue de 1 (CI 95% -4.81;6.81) para la molécula A y 1.82 (IC 95% -4.08;7.74) para la molécula B frente a la molécula O (mmHg). Hubo un caso de hipotensión arterial en cada grupo. Conclusión: Los resultados sugieren que desde un punto de vista farmacodinámico las moléculas innovadora y genéricas de Remifentanil son similares para la laringo-scopia/intubación con dosis TCI de 6, 8 y 10 ng/ml.

Un resumen de la investigación en tromboelastografía / An overview of thrombelastography research

Introducción: La tromboelastografía (TEG) es un método para valorar las características de la formación y destrucción del coágulo. Una variedad de aplicaciones han sido sugeridas en la literatura. Objetivo: Proporcionar un resumen acerca del conocimiento actual de las aplicaciones de la TEG. Métodos: Se realizó una búsqueda en la base de datos PubMed hasta julio de 2012 con el término «Thrombelastography [MeSH Terms]¼. Se analizaron artículos de estudios retrospectivos y prospectivos, revisiones y guías conteniendo información acerca de las aplicaciones de la TEG escritos en inglés y español. Resultados: La búsqueda arrojó 3.139 artículos desde 1962. Se clasificaron en 8 categorías: 862 (27,6%) asociados a enfermedades no quirúrgicas, 294 (9,4%) a trasplante hepático, 711 (22,6%) a investigación básica, 174 (5,5%) a obstetricia, 228 (7,3%) a cirugía cardiovascular, 177 (5,6%) a otras cirugías, 234 (7,4%) a técnicas anestésicas y 459 (14,6%) a fármacos. Conclusión: La TEG como herramienta diagnóstica y para guiar terapia transfusional está en aumento. La TEG aún continúa en estudio en diferentes áreas del conocimiento clínico y aún falta definir adecuadamente los alcances de esta técnica diagnóstica. Es evidente que se debe hacer un uso racional de la TEG, conocer a fondo sus fortalezas y debilidades y continuar explorando nuevas aplicaciones.

Introduction: Thrombelastography (TEG) is a method to assess clot formation and destruction. Various applications have been suggested in the literature. Objective: To provide an overview of the current knowledge about TEG applications. Methods: Adatabase search in PubMed was performed up to July 2012 using the term "Thrombelastography [MeSH Terms]". We analysed retrospective and prospective studies, reviews and guidelines with information about the applications of TEG written in English and Spanish. Results: The search resulted in 3139 papers since 1962. These were classified in 8 categories: 862 (27.6%) in non-surgical diseases, 294 (9.4%) in liver transplant, 711 (22.6%) in basic research, 174 (5.5%) in obstetrics, 228 (7.3%) in cardiovascular surgery, 177 (5.6%) in other types of surgery, 234 (7.4%) in anaesthetic techniques, and 459 (14.6%) in relation with medications. Conclusion: The application of TEG as a diagnostic tool and as a guide in transfusion therapy is increasing. Its use is still in development in different clinical fields and the advantages and limitations of this technique still have to be defined. It is evident that thrombelastography should be used with caution, and its strengths and weaknesses as well as new applications must continue to be explored.

Inotrópicos en el postoperatorio de cirugía cardiovascular: estudio de corte transversal / Inotropes in postoperative cardiovascular surgery: cross-sectional study

Introducción: Los inotrópicos, fármacos de uso frecuente en la unidad de cuidado intensivo, se emplean con el fin de mantener la perfusión tisular en los diferentes estados de choque mientras se resuelve la etiología del mismo. Los pacientes programados para cirugía cardiovascular son un subgrupo que con frecuencia requiere tratamiento con estos fármacos en el postoperatorio. Objetivo: Describir la frecuencia y el tipo de fármacos usados para el soporte hemodinámico de pacientes en el postoperatorio de cirugía cardiovascular electiva en la Clínica Fundadores, Bogotá, DC. Métodos: Estudio de corte trasversal, en el que se incluyeron todos los pacientes que ingresaron en la unidad de cuidado intensivo sin requerimiento de soporte hemodinámico farmacológico entre octubre de 2010 y diciembre de 2011 en postoperatorio de cirugía cardiaca. Se extrajeron de las historias clínicas electrónicas la edad, el sexo, el puntaje EuroSCORE, el diagnóstico prequirúrgico, el uso de circulación extracorpórea, el uso de fármacos vasoactivos, los días de estancia en la unidad de cuidado intensivo y la mortalidad. Resultados: Se encontraron 150 registros de cirugía cardiovascular con una edad media de 62,8 años (DE 10,5), de los cuales 97 (64,6%) eran hombres. Se encontraron 22 (15%) casos con EuroSCORE en riesgo alto, 93 (62%) en riesgo moderado y 35 (23%) en riesgo bajo. Los diagnósticos prequirúrgicos incluyeron enfermedad coronaria en 105 (70%) pacientes, valvulopatías en 29 (19%), cardiopatía isquémica y valvular en 9 (6%) y comunicación interauricular en 6 (4%). En 57 (38%) casos se empleó circulación extracorpórea con un tiempo medio (RIQ) de 92 (73-114) minutos, de quienes 55 se operaron con clamp aórtico, con un tiempo medio (RIQ) de 75 (52-90) minutos. En 78 (52%) pacientes se utilizó uno o más fármacos vasoactivos, siendo la adrenalina el de mayor frecuencia en 41 (27%) casos. Los pacientes que necesitaron inodilatadores fueron 22 (15%) y recibieron dobutamina. La mediana (RIQ) de estancia en la unidad de cuidados intensivos fue de 3 (2-4) días y murieron 6 (4,7%) pacientes. Conclusión: En casi la mitad de los pacientes en postoperatorio de cirugía cardiovascular se utilizó un agente inotrópico, de los cuales la adrenalina fue la más frecuente, seguida de la norepinefrina; el inodilatador utilizado fue la dobutamina. No se utilizaron inotrópicos sensibilizadores del calcio y en baja frecuencia inhibidores de la fosfodiesterasa III con resultados similares en cuanto a estancia en la unidad de cuidados intensivos y mortalidad respecto a estudios en otras poblaciones.

Background: Inotropes are frequently used in the intensive care unit to maintain tissue perfusion in case of shock while the cause is resolved. Patients who undergo cardiovascular surgery will frequently require treatment with these drugs during postoperative care. Aim: To describe the frequency and type of drugs used for the hemodynamic support of patients during the postoperative period of elective cardiovascular surgery at ClínicaFundadores, Bogotá D.C. Methods: Cross-sectional study. All patients in the postoperative period of cardiovascular surgery admitted to the intensive care unit (ICU) without pharmacologic hemodynamic support between October and December 2011 were included. The following variables were obtained from the electronic medical records: age, sex, EuroSCORE, pre-surgical diagnosis, use of cardiopulmonary bypass (CPB), use of vasoactive drugs, days of ICU stay and mortality. Results: One-hundred fifty cases of cardiovascular surgery were found. Patients had a mean age of 62.8 years (SD 10.5), of whom 97 (64.6%) were men. Risk according to Euro SCORE was high in 22 (15%) cases, moderate in 93 (62%) and low in 35 (23%) cases. Pre-surgical diagnoses included coronary artery disease in 105 (70%) patients, valvular disease in 29 (19%) patients, ischemic and valvular cardiomyopathy in 9 patients (6%) and atrial septal defect in 6 (4%) patients. CPB was used in 57 (38%) cases with a median (IQR) time of 92 (73-114) minutes, of whom 55 (52%) patients were operated with aortic clamp, with a median (IQR) time of 75 (52-90) minutes. In 78 (52%) patients one or more vasoactive drugs were used, where adrenaline was used most often (41 patients, 27%). In 22 (15%) patients inodilators were required. These patients received dobutamine. Median (IQR) ICU stay was 3 (2-4) days and 6 (4.7%) patients died. Conclusion: In almost half of patients in the postoperative period of cardiovascular surgery an inotrope was used; the most frequently being adrenaline followed by norepinephrine. The inodilator used in these patients was dobutamine. No calcium sensitizer inotropes were used and in few cases phosphodiesterase III inhibitors were used with comparable ICU stay and mortality to research in other populations.

Evaluación de la mutagenicidad causada por metales pesados presentes en agua del río Cauca en la ciudad de Cali, Colombia / Mutagenicity evaluation caused by heavy metals found in Cauca river water in the city of Cali, Colombia / Avaliação de mutagenicidade causados por metais pesados encontrados na água do rio de água Cauca na cidade de Cali, Colômbia

Se evaluó la mutagenicidad del agua del río Cauca debida a la presencia de metales pesados en la zona urbana de la Ciudad de Santiago de Cali, a partir de muestras tomadas en la temporada seca y lluviosa en el año 2013. Los metales se extrajeron pasando el agua por la resina Amberlite XAD-16. Las concentraciones de los metales pesados se midieron por absorción atómica y la mutagenicidad se evaluó por medio del test de Ames, con las cepas TA98 y TA100 de Salmonella typhimurium con y sin activador enzimático S9. Los resultados mostraron índices de mutagenicidad (IM) positivos (IM > 2,0) para muestras colectadas en temporada lluviosa en tres de los cinco puntos evaluados: puente El Hormiguero (IM = 3,6), desembocadura del Canal Colector Sur (IM = 2,9) y desembocadura del río Cali (IM = 2,7), todos con la cepa TA98 sin S9. Estos sitios presentaron a su vez las mayores concentraciones totales de metales pesados en sus extractos. El análisis de la variación espacio-temporal del índice mutagénico se realizó haciendo un análisis de varianza multifactorial del IM. Los resultados encontrados indican que la época de muestreo contribuye significativamente a la variabilidad del IM , mientras que los puntos de muestreo no.

The mutagenicity of the Cauca River water due to the presence of heavy metals was evaluated in the urban area of the city of Santiago de Cali, from samples taken during the rainy and dry season of 2013. The metals were extracted from water samples using the resin Amberlite XAD-16. The concentrations of heavy metals were measured by atomic absorption and mutagenicity was evaluated by the Ames test, using the TA98 and TA100 strains of Salmonella typhimurium with and without the S9 enzymatic activator. The results showed mutagenicity indices (MI > 2.0) in three of the five points evaluated: El Hormiguero Bridge (MI = 3.6), the mouth of southern collector channel (MI = 2.9) and the mouth of Cali River (MI = 2.7), all with strain TA98 without S9. These sampling points in turn presented the highest total concentrations of heavy metals in the extracts. The determination and analysis of spatio-temporal variation of the mutagenic effects obtained was done by conducting multifactorial variance analysis of MI, finding that the effect of sampling season contributes significantly to the variability of MI unlike the sampling points.

A mutagenicidade da água do rio Cauca, devido à presença de metais pesados foi avaliada-na área urbana da cidade de Santiago de Cali, a partir de amostras coletadas durante as estaçãoes chuvosa e seca em 2013. Os metais foram extraídos, passando a água pela a resina Amberlite XAD-16. As concentrações de metais pesados foram medidas por Absorção Atômica e a mutagenicidade foi avaliada através do teste de Ames, com TA98 e TA100 de Salmonella typhimurium estirpes com e sem S9 activador da enzima. Os resultados mostraram índices de mutagenicidade positiva (MI > 2,0) para amostras coletadas na estação chuvosa em três dos cinco pontos avaliados: El Hormiguero ponte (MI = 3,6), foz do canal coletor (IM = 2, 9) e foz do rio Cali (MI = 2,7), todos com a linhagen TA98 sem S9. Esses locais, a presentaram as maiores concentrações totais de metais pesados em seus extratos. A determinação e análise da variação espaço-temporal do índice mutagénico foi realizada utilizando-se a análise de variância multivariada do IM, sendo encontrado que o efeito da época de amostragem contribui significativamente na a variabilidade de IM ao contrário dos pontos de amostragem.