Impact of a guaranteed access program to imatinib on the survival of patients with chronic myeloid leukemia.

PURPOSE: This work aimed to evaluate the impact of a guaranteed access program to imatinib on the survival of patients with Chronic Myeloid Leukemia. METHODS: We carried out a retrospective, observational, and analytical study of the database of patients diagnosed with Chronic Myeloid Leukemia of the Instituto Nacional de Cancerología and the Hospital General de México Dr. Eduardo to assess overall survival based on guaranteed access or not to imatinib. RESULTS: With an average follow-up of 99 months, all patients' estimated 20-year overall survival was 72% (95% CI, 76-67). A significant difference was found in the 20-year survival probability in favor of patients with guaranteed access 76% (95% CI, 81-71) vs. 61% (95% CI, 69-52) (p < 0.001), in addition to those in which they had better attachment 81.2% (95% CI, 85-76) vs. 44.9% (95% CI, 52-37) (p < 0.001). CONCLUSION: CML is the most frequent chronic leukemia in Mexico. It mainly affects the economically active population (mean age 40), and the prognosis in our country has improved, emulating developed countries; however, the results depend on access to treatment and proper monitoring.

The rs11684747 and rs55790676 SNPs of ADAM17 influence tuberculosis susceptibility and plasma levels of TNF, TNFR1, and TNFR2.

Introduction: The proteolytic activity of A Disintegrin and Metalloproteinase 17 (ADAM17) regulates the release of tumor necrosis factor (TNF) and TNF receptors (TNFRs) from cell surfaces. These molecules play important roles in tuberculosis (TB) shaping innate immune reactions and granuloma formation. Methods: Here, we investigated whether single nucleotide polymorphisms (SNPs) of ADAM17 influence TNF and TNFRs levels in 224 patients with active TB (ATB) and 118 healthy close contacts. Also, we looked for significant associations between SNPs of ADAM17 and ATB status. TNF, TNFR1, and TNFR2 levels were measured in plasma samples by ELISA. Four SNPs of ADAM17 (rs12692386, rs1524668, rs11684747, and rs55790676) were analyzed in DNA isolated from peripheral blood leucocytes. The association between ATB status, genotype, and cytokines was analyzed by multiple regression models. Results: Our results showed a higher frequency of rs11684747 and rs55790676 in close contacts than ATB patients. Coincidentally, heterozygous to these SNPs of ADAM17 showed higher plasma levels of TNF compared to homozygous to their respective ancestral alleles. Strikingly, the levels of TNF and TNFRs distinguished participant groups, with ATB patients displaying lower TNF and higher TNFR1/TNFR2 levels compared to their close contacts. Conclusion: These findings suggest a role for SNPs of ADAM17 in genetic susceptibility to ATB.

Neurolupus como manifestación de primer brote psicótico Reporte de caso / Neurolupus as a manifestation of the first psychotic episode: case report

Resumen Antecedentes: El lupus eritematoso sistémico (LES) es una enfermedad auto inmunitaria crónica multisistémica con diversas manifestaciones clínicas. Siendo las mujeres la pobla ción vulnerable y con mayor afectación a nivel neurológico, al presentar mayor riesgo de convulsiones. Las manifestaciones neuropsiquiátricas ocurren en etapas tempranas de la enfermedad y del diagnóstico, ya que pueden presentarse junto con manifestaciones sistémicas o no. La frecuencia de manifestaciones neuropsiquiátricas en el lupus eritematoso sistémico se ha descrito del 14 al 75%, siendo las alteraciones cognitivas uno de los grandes síntomas a destacar1. La cual puede ir acompañada de trastornos afectivos de tipo depresión y ansiedad. Ya que la psicosis secundaria a LES se remarca por su baja prevalencia (10%)2, los estudios de laboratorio nos suelen orientar hacia el diagnóstico definitivo, siendo los anticuerpos ribosomales P los que se han relacionado más específicamente con la psicosis lúpica. La resonancia magnética es la prueba de elección y las lesiones cerebrales están dominadas por hiperintensidades de materia blanca en forma de punción3. En el siguiente reporte de caso, presentamos a una paciente de 20 años, la cual contaba con antecedentes de esteatosis hepática diagnosticado, diabetes tipo MODY y resección de ovario derecho por teratoma maduro de 9 años de evolución, pero sin antecedentes psiquiátricos de importancia para el momento de su valoración. Sin embargo, de forma aguda presentó un brote psicótico caracterizado por ideas delirantes de grandiosidad y referencia, así como alteraciones conductuales, cognitivas y afectivas. Por las que tuvieron que acudir a hospital de 3er nivel durante el periodo de contingencia sanitaria en el 2020. Tras el antecedente de presentar infección por SARS-CoV-2 tres meses antes de su patología neuropsiquiátricas. Se sospechó en síntomas neurológicos secundarios a infección por COVID-19, así como patología psiquiátrica aislada. Por lo que se realizó abordaje de estudio de primer brote psicótico, diagnosticándose lupus eritematoso sistémico con manifestaciones neuropsiquiátricas. El tratamiento se basó en un bolo de metilprednisolona y antipsicóticos, luego modificada por terapia con corticoesteroides orales y antipsicótico de depósito. Conclusión: El lupus eritematoso sistémico con manifestaciones neuropsiquiátricas es una presentación poco frecuente del padecimiento, por la amplia variación en la aparición de este, los pacientes con síntomas psiquiátricos en contexto de hospital general deben de ser tomados en cuenta para abordajes extensos4. De la misma forma, el tener este conocimiento del caso podrá ampliar nuestro conocimiento sobre las complicaciones de esta patología reumatológica. Y una de sus complicaciones más graves como la psicosis lúpica para poder realizar un mejor abordaje del primer brote psicótico en hospitales generales, donde la valoración de un especialista puede ser más complicada para mejorar las condiciones médicas de estos pacientes.

Abstract Background: Systemic lupus erythematosus is a chronic multisystemic autoimmune disease with diverse clinical manifestations. Women are the most vulnerable population and have the greatest neurological involvement with a higher risk of seizures. Neuropsychiatric manifestations occur in early stages of the disease and diagnosis since they can occur together with systemic manifestations or not. The frequency of neuropsychiatric manifestations in systemic lupus erythematosus has been described from 14 to 75%; being cognitive alterations one of the major symptoms to highlight. Which, in the same way can be accompanied by affective disorders such as depression and anxiety. Since psychosis, secondary to SLE, stands out for its low prevalence (10%), laboratory studies usually guide us towards a definitive diagnosis, being ribosomal P antibodies the ones that have been more specifically related to lupus psychosis. MRI is the test of choice and brain lesions are dominated by punctate white matter hyperintensities. In the following case report, we present a 20-year-old patient who had a history of diagnosed hepatic steatosis, MODY type diabetes and resection of the right ovary for mature teratoma of 9 years of evolution; but with no psychiatric history of importance at the time of her evaluation. However, she acutely presented a psychotic outbreak characterized by delusions of grandiosity and reference; as well as behavioral, cognitive, and affective alterations. For which she had to go to a 3rd level hospital during the period of health contingency in 2020. After a history of SARS-CoV-2 infection three months before her neuropsychiatric pathology, neurological symptoms secondary to COVID-19 infection were suspected, as well as isolated psychiatric pathology. Therefore, a study approach of the first psychotic outbreak was performed, diagnosing systemic lupus erythematosus with neuropsychiatric manifestations. Treatment was based on a bolus of methylprednisolone and antipsychotics; later modified by therapy with oral corticosteroids and depot antipsychotic. Conclusion: Systemic lupus erythematosus with neuropsychiatric manifestations is an infrequent presentation of the disease, because of the wide variation in its appearance, patients with psychiatric symptoms in a general hospital setting should be considered for extensive approaches. In the same way, having this knowledge of this case may broaden our knowledge about the complications of this rheumatologic pathology. And one of its most serious complications such as lupus psychosis to be able to make a better approach to the first psychotic outbreak in general hospitals, where the assessment of a specialist can be more complicated.

Mortality Analysis of Patients with COVID-19 in Mexico Based on Risk Factors Applying Machine Learning Techniques.

The new pandemic caused by the COVID-19 virus has generated an overload in the quality of medical care in clinical centers around the world. Causes that originate this fact include lack of medical personnel, infrastructure, medicines, among others. The rapid and exponential increase in the number of patients infected by COVID-19 has required an efficient and speedy prediction of possible infections and their consequences with the purpose of reducing the health care quality overload. Therefore, intelligent models are developed and employed to support medical personnel, allowing them to give a more effective diagnosis about the health status of patients infected by COVID-19. This paper aims to propose an alternative algorithmic analysis for predicting the health status of patients infected with COVID-19 in Mexico. Different prediction models such as KNN, logistic regression, random forests, ANN and majority vote were evaluated and compared. The models use risk factors as variables to predict the mortality of patients from COVID-19. The most successful scheme is the proposed ANN-based model, which obtained an accuracy of 90% and an F1 score of 89.64%. Data analysis reveals that pneumonia, advanced age and intubation requirement are the risk factors with the greatest influence on death caused by virus in Mexico.

Covered intestinal endoprosthesis for the management of enteroatmospheric fistula, case report and review of the literature.

The management of fistulas is a challenge for surgeons, the enteroatmospheric fistulas are characterized by being superficial, high debit and surrounded by viscera or granulation tissue, with poor control of its excretion due to their anatomy. We describe an alternative approach to the management of enteroatmospheric fistulas, in a patient with a hostile abdomen and massive intestinal resection, selected for placement of a stent, as a rescue measure. Use of intestinal stent allowed fistula control and enteric feeding capacity, that substantially improves the quality of life.

El manejo de la fístula es un desafío para los cirujanos. Las fístulas enteroatmosféricas (EAF) se caracterizan por ser superficiales, de alto gasto y rodeadas de vísceras o tejido de granulación, con un control deficiente de su excreción debido a su anatomía. Describimos un enfoque alternativo para el manejo de la fístula enteroatmosférica, en un paciente con un abdomen hostil y resección intestinal masiva, seleccionándolo para la colocación de stent como medida de rescate, permitiendo el control de la fístula y el inicio de la alimentación entérica, lo que mejora sustancialmente la calidad de vida.

Robust Discovery of Mild Cognitive Impairment Subtypes and Their Risk of Alzheimer's Disease Conversion Using Unsupervised Machine Learning and Gaussian Mixture Modeling.

BACKGROUND: Alzheimer's Disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills. The ability to correctly predict the diagnosis of Alzheimer's disease in its earliest stages can help physicians make more informed clinical decisions on therapy plans. OBJECTIVE: This study aimed to determine whether the unsupervised discovering of latent classes of subjects with Mild Cognitive Impairment (MCI) may be useful in finding different prodromal AD stages and/or subjects with a low MCI to AD conversion risk. METHODS: Total 18 features relevant to the MCI to AD conversion process led to the identification of 681 subjects with early MCI. Subjects were divided into training (70%) and validation (30%) sets. Subjects from the training set were analyzed using consensus clustering, and Gaussian Mixture Models (GMM) were used to describe the latent classes. The discovered GMM predicted the latent class of the validation set. Finally, descriptive statistics, rates of conversion, and Odds Ratios (OR) were computed for each discovered class. RESULTS: Through consensus clustering, we discovered three different clusters among MCI subjects. The three clusters were associated with low-risk (OR = 0.12, 95%CI = 0.04 to 0.3|), medium-risk (OR = 1.33, 95%CI = 0.75 to 2.37), and high-risk (OR = 3.02, 95%CI = 1.64 to 5.57) of converting from MCI to AD, with the high-risk and low-risk groups highly contrasting. Hence, prodromal AD subjects were present in only two clusters. CONCLUSION: We successfully discovered three different latent classes among MCI subjects with varied risks of MCI-to-AD conversion through consensus clustering. Two of the discovered classes may represent two different prodromal presentations of Alzheimer´s disease.

Influence of Potato Crisps Processing Parameters on Acrylamide Formation and Bioaccesibility.

A fractional factorial design was used to evaluate the effects of temperature, frying time, blanching treatment and the thickness of potato slices on acrylamide content in crisps. The design was used on freshly harvested and four-month stored potatoes. The critical factors found were temperature and frying time, and the interaction between blanching treatment and slice thickness. Once frying conditions were selected, an acrylamide content of 725 and 1030 mg kg-1 was found for non-stored and 4-month stored tubers, with adequate textural parameters in both cases. The difference in concentration is related to storage conditions, which must be controlled in order to control acrylamide levels. Bioaccesibility studies demonstrated that acrylamide concentration remained at 70%, and reductions took place mainly at the intestinal phase, as a result of reaction with nucleophilic compounds.

Different gene expression profiles in subcutaneous & visceral adipose tissues from Mexican patients with obesity.

Background & objectives: Obesity is a health problem that requires substantial efforts to understand the physiopathology of its various types and to determine therapeutic strategies for its treatment. The objective of this study was to characterize differences in the global gene expression profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) between control patients (normal weight) and patients with obesity (IMC≥30) using microarrays. Methods: Employing RNA isolated from SAT and VAT samples obtained from eight control and eight class I, II and III patients with obesity, the gene expression profiles were compared between SAT and VAT using microarrays and the findings were validated via real-time quantitative polymerase chain reaction. Results: A total of 327 and 488 genes were found to be differentially expressed in SAT and VAT, respectively (P≤0.05). Upregulation of PPAP2C, CYP4A11 and CYP17A1 genes was seen in the VAT of obese individuals. Interpretation & conclusions: SAT and VAT exhibited significant differences in terms of the expression of specific genes. These genes might be related to obesity. These findings may be used to improve the clinical diagnosis of obesity and could be a tool leading to the proposal of new therapeutic strategies for the treatment of obesity.

Violencias institucionales y reproducción de estigmas en usuarios de cocaínas fumables de Montevideo / Institutional violence and stigma reproduction on smoked cocaine users in Montevideo

A través de las oposiciones legal/ilegal y legítimo/ilegítimo, nos proponemos estudiar el discurso de los derechos humanos y su vulneración cotidiana en relación a los usuarios de cocaínas fumables en Montevideo, Uruguay. Esos sujetos pertenecen a los sectores más pobres de la sociedad y se encuentran notoriamente afectados por el estigma, la violencia y la desigualdad. El trabajo recoge resultados de un proceso de investigación etnográfíco con usuarios de cocaínas fumables y muestra cómo la continuidad de la violencia configura los cuerpos y las identidades de los sujetos, de tal forma que se les dificulta participar de otras redes distintas a las del mercado ilegal, así como emprender los procesos de rehabilitación social y sanitaria.(AU)

By means of the legal/illegal and legitimate/illegitimate categories, we propose to study the discourse of human rights and their everyday vulnerability regarding smoked cocaine users in Montevideo, Uruguay. Thse subjects belong to the poorest places of the population, and are notoriously affcted by stigma, structural violence, and inequality. This work summarizes the results of an ethnographic research process with users of smoked cocaine, and shows how the continuum of violence sets the bodies and identities of the subjects in a way that makes their participation harder in networks other than in the illegal market. It also aims at conducting processes of social and health rehabilitation.(AU)

Violencias institucionales y reproducción de estigmas en usuarios de cocaínas fumables de Montevideo / Institutional violence and stigma reproduction on smoked cocaine users in Montevideo

A través de las oposiciones legal/ilegal y legítimo/ilegítimo, nos proponemos estudiar el discurso de los derechos humanos y su vulneración cotidiana en relación a los usuarios de cocaínas fumables en Montevideo, Uruguay. Esos sujetos pertenecen a los sectores más pobres de la sociedad y se encuentran notoriamente afectados por el estigma, la violencia y la desigualdad. El trabajo recoge resultados de un proceso de investigación etnográfíco con usuarios de cocaínas fumables y muestra cómo la continuidad de la violencia configura los cuerpos y las identidades de los sujetos, de tal forma que se les dificulta participar de otras redes distintas a las del mercado ilegal, así como emprender los procesos de rehabilitación social y sanitaria.

By means of the legal/illegal and legitimate/illegitimate categories, we propose to study the discourse of human rights and their everyday vulnerability regarding smoked cocaine users in Montevideo, Uruguay. Thse subjects belong to the poorest places of the population, and are notoriously affcted by stigma, structural violence, and inequality. This work summarizes the results of an ethnographic research process with users of smoked cocaine, and shows how the continuum of violence sets the bodies and identities of the subjects in a way that makes their participation harder in networks other than in the illegal market. It also aims at conducting processes of social and health rehabilitation.

Compact cancer biomarkers discovery using a swarm intelligence feature selection algorithm.

Biomarker discovery is a typical application from functional genomics. Due to the large number of genes studied simultaneously in microarray data, feature selection is a key step. Swarm intelligence has emerged as a solution for the feature selection problem. However, swarm intelligence settings for feature selection fail to select small features subsets. We have proposed a swarm intelligence feature selection algorithm based on the initialization and update of only a subset of particles in the swarm. In this study, we tested our algorithm in 11 microarray datasets for brain, leukemia, lung, prostate, and others. We show that the proposed swarm intelligence algorithm successfully increase the classification accuracy and decrease the number of selected features compared to other swarm intelligence methods.

Rapid eye-fixation training without eyetracking.

Maintenance of stable central eye fixation is crucial for a variety of behavioral, electrophysiological, and neuroimaging experiments. Naive observers in these experiments are not typically accustomed to fixating, either requiring the use of cumbersome and costly eyetracking or producing confounds in results. We devised a flicker display that produced an easily detectable visual phenomenon whenever the eyes moved. A few minutes of training using this display dramatically improved the accuracy of eye fixation while observers performed a demanding spatial attention cuing task. The same amount of training using control displays did not produce significant fixation improvements, and some observers consistently made eye movements to the peripheral attention cue, contaminating the cuing effect. Our results indicate that (1) eye fixation can be rapidly improved in naive observers by providing real-time feedback about eye movements, and (2) our simple flicker technique provides an easy and effective method for providing this feedback.