Genome sequencing reveals molecular subgroups in oral epithelial dysplasia

Abstract This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

Construcción de recursos de texto para la identificación automática de información clínica en narrativas no estructuradas / Construction of text resources for automatic identification of clinical information in unstructured narratives

Background: A significant proportion of the clinical record is in free text format, making it difficult to extract key information and make secondary use of patient data. Automatic detection of information within narratives initially requires humans, following specific protocols and rules, to identify medical entities of interest. Aim: To build a linguistic resource of annotated medical entities on texts produced in Chilean hospitals. Material and Methods: A clinical corpus was constructed using 150 referrals in public hospitals. Three annotators identified six medical entities: clinical findings, diagnoses, body parts, medications, abbreviations, and family members. An annotation scheme was designed, and an iterative approach to train the annotators was applied. The F1-Score metric was used to assess the progress of the annotator's agreement during their training. Results: An average F1-Score of 0.73 was observed at the beginning of the project. After the training period, it increased to 0.87. Annotation of clinical findings and body parts showed significant discrepancy, while abbreviations, medications, and family members showed high agreement. Conclusions: A linguistic resource with annotated medical entities on texts produced in Chilean hospitals was built and made available, working with annotators related to medicine. The iterative annotation approach allowed us to improve performance metrics. The corpus and annotation protocols will be released to the research community.

Factores pronósticos de la supervivencia del paro cardíaco extrahospitalario en Montevideo. Análisis de cinco años / Predictive factors for out-of-hospital cardiac arrest survival in Montevideo. Five year analysis

Introducción: las enfermedades cardíacas son la principal causa de muerte en Uruguay. Se estima que la mitad de estos fallecimientos se presentan como un paro cardíaco dentro de la primera hora de inicio de los síntomas. Material y método: estudio descriptivo-analítico, retrospectivo, de los paros cardíacos extrahospitalarios no traumáticosde adultos asistidos entre los años 2007 y 2011 en Montevideo. Se realizó test de chi cuadrado, test de t y regresión logísticapara el análisis de asociación de variables. Resultados: se asistieron 692 pacientes con edad promedio de 71,5 años, sexo masculino 57,2%. La mediana del tiempo recepción del llamado-arribo fue de 9 minutos. Los ritmos al arribo: asistolía 59,3%, fibrilación ventricular 22,6%, actividadeléctrica sin pulso 16,8% y taquicardia ventricular sin pulso 1,01%. La supervivencia al ingreso hospitalario fue de21,2%. En el análisis univariado con respecto a la sobrevida intrahospitalaria se observó significación estadística en las variables: vía pública como lugar del evento (p=0,0004), fibrilación ventricular (p<0,0001), taquicardia paroxística supraventricular(p = 0,01) y asistolía (p < 0,0001) como ritmos al arribo y edad (p = 0,004). Cuando se consideraron en conjunto los ritmos desfibrilables, se asociaron a mayor sobrevida intrahospitalaria (p<0,0001). En el análisis multivariado con respecto a la sobrevida intrahospitalaria se observó significación estadística en la variable ritmos desfibrilables(p < 0,0001). Conclusión: hubo tiempos de respuesta adecuados de la emergencia móvil. La sobrevida intraospitalaria fue similar a la referida en estudios internacionales. Los paros cardíacos extrahospitalarios en ritmos desfibrilables, la vía pública como el lugar donde acontece el evento y las edades más bajas se asociaron a mayor sobrevida intrahospitalaria.

ntroduction: cardiovascular diseases are the leading cause of death in Uruguay. Is estimated that half of these deaths presents as cardiac arrest within the first hour of onset of symptoms.Methods: this is a retrospective descriptive-analytic study of nontraumatic adult out of hospital cardiac arrest (OHCA) between 2007 and 2011 in Montevideo. We performed chi-square test, t test and logistic regression to analyze the association of variables.Results: 692 patients were treated by non-traumatic OHCA. The average age was 71.5 y.o., 57.2% male. The median time of the call-arrival reception was 9 minutes. The rhythms on arrival were: asystole 59.3%, ventricular fibrillation 22.6%, pulseless electrical activity 16.8% and pulseless ventricular tachycardia 1.01%. The survival to hospital admission (SHA) was 21.2%. In univariate analysis in reference to the SHA statistical significance was observed in the following variables: public place (p = 0.0004), ventricular fibrillation (p <0.0001), PVT (p = 0.01), asystole (p <0.0001) and age (p = 0.004). When considered together shockable rhythms were associated with greater SHA (p <0.0001). In multivariate analysis referred to to the SHA statistical significance was observed in the variable shockable rhythms (p <0.0001).Conclusion: Times of emergency response were acceptable.Survival to hospital admission is similar to that reported in international studies. The OHCA shockable rhythms, a public place where the event occurs and lower age were associated with more survival to hospital admission.

Laparoscopía y apendicectomía laparoscópica en niños: experiencia nacional / Laparoscopy and laparoscopic appendectomy in children: national experience

Introducción: la apendicitis aguda es la urgencia quirúrgica más frecuente en niños. Las dificultades diagnósticas determinan un porcentaje de apendicitis evolucionadas o de apendicectomías innecesarias. La morbilidad y la incidencia de estos eventos disminuye con la laparoscopía. Objetivo: presentar nuestra experiencia laparoscópica en niños, compararla con los trabajos internacionales y con la laparotomía en nuestro medio. Metodología: se realizó un trabajo retrospectivo de las laparoscopías diagnósticas (LD) y apendicectomías laparoscópicas (AL) en el período 2001-2009 . Se consideró: edad, sexo, tipo de apendicitis, tiempo quirúrgico, conversión, complicaciones, reintervención, estadía hospitalaria, antibioticoterapia, e histología. Se dividió la serie en un primer período de 50 apendicectomías en el que hubo criterios de exclusión, y un segundo de 75 en el que se desarrolló un aprendizaje tutorizado. Se compararon los dos períodos de la serie de AL entre sí, y la serie de AL con una serie local de apendicectomizados por vía abierta (AA). Las variables categóricas de interés se analizaron mediante test de Chi cuadrado, test de Fisher y test t de student, utilizando el programa Epi-info6. Resultados: se realizaron 164 procedimientos: 125 AL y 39 LD. Las primeras 50 AL se realizaron en 60 meses, y las 75 siguientes en 40. En el CHPR se realizaron 91 AL. La media de edad fue 10,2 (DE 1,9). Predominaron el sexo masculino (59%) y la apendicitis simple, que correspondió al 60,8% (76 casos). El índice de conversión en la serie fue de 4,8%, con disminución significativa (p=0,03) del primer período (10%) al segundo (1,3%). Hubo diferencia significativa (p de 0,002) en el tiempo quirúrgico entre el primer período (media 40’, DE 15,8) y el segundo (media 32’, DE 7,7). El índice de infección de la herida operatoria (IHO) en AL fue de 0,8% (un caso) y el de infección abdominal (IA) fue de 1,6% (dos casos)...

Introduction: acute appendicitis is the most common surgical emergency in children. The diagnostic difficulties determine a percentage of evolved appendicitis or unnecessary appendectomies. The morbidity and the incidence of these events diminishes with laparoscopy. Objective: to present our experience with laparoscopy in children, compared with international papers and laparotomy in our country.Method: we conducted a retrospective study of diagnostic laparoscopy (DL) and laparoscopic appendectomy (LA) in the period 2001-2009. Were considered: age, sex, type of appendicitis, surgical time, conversion, complications, reoperation, hospital stay, antibiotic therapy, and histology. We divided the series into a first period of 50 appendectomies in which there were exclusion criteria, and another 75 in which supervised learning was developed. We compared two periods of the AL series between themselves, and the number of AL with a local number with open appendectomy (AA). The categorical variables of interest were analyzed by Chi square, Fisher test and Student t test, using Epi-info 6.Results: 164 procedures were conducted: 125 AL and 39 LD. The first 50 were done in 60 months, and the following 75 in 40. The 91 were held CHPR AL. The mean age was 10.2 (SD 1.9). Males (59%) and simple appendicitis, which corresponded to 60.8% (76 cases), predominated. The conversion rate in the range was 4.8%, with significant reduction (p=0.03) from the first period (10%) to second (1.3%). There were significant reduction (p=0.002) in surgical time between the first period (average 40, DE 15.8) and second (mean 32', DE 7.7). The rate of surgical wound infection (SWI) in LA was 0.8% (one case) and abdominal infection (AI) was 1.6% (two cases). The AI and SWI in the series of AL was lower compared to the number of AA, with a significant reduction in SWI (p 0.001)...