Understanding factors limiting hematopoietic cell transplantation for acute myeloid leukemia patients in Mexico: a comprehensive analysis.

Acute myeloid leukemia (AML) is the most frequent indication for allogeneic hematopoietic cell transplantation (alloHCT) worldwide; social and health system barriers limit its access. We performed an observational retrospective analysis in Mexico to analyze factors limiting alloHCT in fit patients with AML. With a median follow-up of 11.8 months, 301 patients were included, with a median age of 42; 33.5% were classified as adverse risk. Despite 215 patients (92.5%) achieving complete remission, only 103 (34%) had HLA-typing: 44.5% had a matched-sibling donor (MSD), 32% a haploidentical donor, and 23.5% had no donor. Only 23.5% of patients had an HCT consult; merely 36 underwent an HCT: 30 alloHCT, and six an autologous HCT. Age ≥ 60 years, HCT-CI score ≥ three, and the absence of a local transplant program negatively influenced HLA typing likelihood. Patients with an MSD had a higher alloHCT likelihood. The cumulative incidence of transplant (CIT) and relapse (CIR) at 6 and 12 months was 7.3% and 13.8%, 8.2% and 13%, respectively. A lack of HLA-typing was associated with a lower CIT (p < 0.001) and higher CIR (p = 0.033) (HR 11.72, CI 95% 4.39-31.27, p < 0.001), while the presence of an MSD was associated with a higher CIT (p = 0.002) (HR 4.22, CI 95% 1.89-9.44, p < 0.001). The main reasons hindering alloHCT are the lack of access to HLA-typing tests and the absence of an MSD. A national donor registry and improved HLA-typing accessibility are critical for increasing alloHCT access in Mexico.

Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.

Cordycepin, or 3'-deoxyadenosine, is an adenosine analog with a broad spectrum of biological activity. The key structural difference between cordycepin and adenosine lies in the absence of a hydroxyl group at the 3' position of the ribose ring. Upon administration, cordycepin can undergo an enzymatic transformation in specific tissues, forming cordycepin triphosphate. In this study, we conducted a comprehensive analysis of the structural features of cordycepin and its derivatives, contrasting them with endogenous purine-based metabolites using chemoinformatics and bioinformatics tools in addition to molecular dynamics simulations. We tested the hypothesis that cordycepin triphosphate could bind to the active site of the adenylate cyclase enzyme. The outcomes of our molecular dynamics simulations revealed scores that are comparable to, and superior to, those of adenosine triphosphate (ATP), the endogenous ligand. This interaction could reduce the production of cyclic adenosine monophosphate (cAMP) by acting as a pseudo-ATP that lacks a hydroxyl group at the 3' position, essential to carry out nucleotide cyclization. We discuss the implications in the context of the plasticity of cancer and other cells within the tumor microenvironment, such as cancer-associated fibroblast, endothelial, and immune cells. This interaction could awaken antitumor immunity by preventing phenotypic changes in the immune cells driven by sustained cAMP signaling. The last could be an unreported molecular mechanism that helps to explain more details about cordycepin's mechanism of action.

Identification of variants in genes associated with hypertrophic cardiomyopathy in Mexican patients.

The objective of this work was to identify genetic variants in Mexican patients diagnosed with hypertrophic cardiomyopathy (HCM). According to world literature, the genes mainly involved are MHY7 and MYBPC3, although variants have been found in more than 50 genes related to heart disease and sudden death, and to our knowledge there are no studies in the Mexican population. These variants are reported and classified in the ClinVar (PubMed) database and only some of them are recognized in the Online Mendelian Information in Men (OMIM). The present study included 37 patients, with 14 sporadic cases and 6 familial cases, with a total of 21 index cases. Next-generation sequencing was performed on a predesigned panel of 168 genes associated with heart disease and sudden death. The sequencing analysis revealed twelve (57%) pathogenic or probably pathogenic variants, 9 of them were familial cases, managing to identify pathogenic variants in relatives without symptoms of the disease. At the molecular level, nine of the 12 variants (75%) were single nucleotide changes, 2 (17%) deletions, and 1 (8%) splice site alteration. The genes involved were MYH7 (25%), MYBPC3 (25%) and ACADVL, KCNE1, TNNI3, TPM1, SLC22A5, TNNT2 (8%). In conclusion; we found five variants that were not previously reported in public databases. It is important to follow up on the reclassification of variants, especially those of uncertain significance in patients with symptoms of the condition. All patients included in the study and their relatives received family genetic counseling.

What Do We Currently Know About Chronic Myeloid Leukemia (CML) and COVID-19?

PURPOSE OF REVIEW: COVID-19 is highly contagious; since it was first identified, the virus has rapidly spread to more than 100 countries and was declared a pandemic on March 11, 2020, by the World Health Organization (WHO). This disease presents several challenges when managing patients with leukemia. We review the information about chronic myeloid leukemia (CML) and COVID-19: risk factors, prognosis, and the role of tyrosine kinase inhibitors (TKIs). RECENT FINDINGS: At present, we find no data suggesting that patients with CML-chronic phase (CML-CP) are at higher risk of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general healthy population. TKIs had been proposed to fight the SARS-CoV-2-related disease (COVID-19). CML patients should continue receiving their TKIs if they have COVID-19 disease. The role of TKIs as protective factors against SARS-CoV-2 infection in patients with CML should be confirmed by large-scale epidemiologic studies.

Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium abscessus: a model to study antimycobacterial agents.

BACKGROUND: Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model using organotypic cultures of murine precision-cut lung slices, an experimental model in which metabolic activity, and all the usual cell types of the organ are found while the tissue architecture and the interactions between the different cells are maintained. METHODS: Precision cut lung slices (PCLS) were prepared from the lungs of wild type BALB/c mice using the Krumdieck® tissue slicer. Lung tissue slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 µg/mL) and tigecycline (0.25, 1 and 4 µg/mL), at 12, 24 and 48 h. Afterwards, CFUs were determined plating on blood agar to measure the surviving intracellular bacteria. The viability of PCLS was assessed by Alamar Blue assay and corroborated using histopathological analysis. RESULTS: PCLS were successfully infected with a virulent strain of M. abscessus as demonstrated by CFUs and detailed histopathological analysis. The time-course infection, including tissue damage, parallels in vivo findings reported in genetically modified murine models for M. abscessus infection. Tigecycline showed a bactericidal effect at 48 h that achieved a reduction of > 4log10 CFU/mL against the intracellular mycobacteria, while imipenem showed a bacteriostatic effect. CONCLUSIONS: The use of this new organotypic ex vivo model provides the opportunity to test new drugs against M. abscessus, decreasing the use of costly and tedious animal models.

Breast Organotypic Cancer Models.

Breast cancer is the most common cancer type diagnosed in women, it represents a critical public health problem worldwide, with 1,671,149 estimated new cases and nearly 571,000 related deaths. Research on breast cancer has mainly been conducted using two-dimensional (2D) cell cultures and animal models. The usefulness of these models is reflected in the vast knowledge accumulated over the past decades. However, considering that animal models are three-dimensional (3D) in nature, the validity of the studies using 2D cell cultures has recently been questioned. Although animal models are important in cancer research, ethical questions arise about their use and usefulness as there is no clear predictivity of human disease outcome and they are very expensive and take too much time to obtain results. The poor performance or failure of most cancer drugs suggests that preclinical research on cancer has been based on an over-dependence on inadequate animal models. For these reasons, in the last few years development of alternative models has been prioritized to study human breast cancer behavior, while maintaining a 3D microenvironment, and to reduce the number of experiments conducted in animals. One way to achieve this is using organotypic cultures, which are being more frequently explored in cancer research because they mimic tissue architecture in vivo. These characteristics make organotypic cultures a valuable tool in cancer research as an alternative to replace animal models and for predicting risk assessment in humans. This chapter describes the cultures of multicellular spheroids, organoids, 3D bioreactors, and tumor slices, which are the most widely used organotypic models in breast cancer research.

Antitumoral Effect of Laurinterol on 3D Culture of Breast Cancer Explants.

Macroalgae represent an important source of bioactive compounds with a wide range of biotechnological applications. Overall, the discovery of effective cytotoxic compounds with pharmaceutical potential is a significant challenge, mostly because they are scarce in nature or their total synthesis is not efficient, while the bioprospecting models currently used do not predict clinical responses. Given this context, we used three-dimensional (3D) cultures of human breast cancer explants to evaluate the antitumoral effect of laurinterol, the major compound of an ethanolic extract of Laurencia johnstonii. To this end, we evaluated the metabolic and histopathological effects of the crude extract of L. johnstonii and laurinterol on Vero and MCF-7 cells, in addition to breast cancer explants. We observed a dose-dependent inhibition of the metabolic activity, as well as morphologic and nuclear changes characteristic of apoptosis. On the other hand, a reduced metabolic viability and marked necrosis areas were observed in breast cancer explants incubated with the crude extract, while explants treated with laurinterol exhibited a heterogeneous response which was associated with the individual response of each human tumor sample. This study supports the cytotoxic and antitumoral effects of laurinterol in in vitro cell cultures and in ex vivo organotypic cultures of human breast cancer explants.

Synthesis, antimycobacterial and cytotoxic activity of α,ß-unsaturated amides and 2,4-disubstituted oxazoline derivatives.

The synthesis of six α,ß,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a MIC of 14.2, 13.6 and 10.8µM, respectively, and the compounds (S)-3d,f were the most active against resistant strain with a MIC of 6.8 and 7.4µM. The ex-vivo evaluation of hepatotoxicity on precision-cut rat liver slices was also tested for the α,ß-unsaturated amides (S)-2b and (S)-2d,f and for the oxazolines (S)-3b and (S)-3d,f at different concentrations (5, 15 and 30µg/mL). The results indicate that these compounds possess promising antimycobacterial activity and at the same time are not hepatotoxic. These findings open the possibility for development of new drugs against tuberculosis.

[Myocardial infarction in young mexicans associated to metabolic syndrome]. / Infarto agudo al miocardio en jóvenes mexicanos asociado a síndrome metabólico.

BACKGROUND: Acute coronary diseases are catastrophic, especially in young patients. OBJECTIVE: To determine the risk of metabolic syndrome (MS) for premature acute myocardial infarction (AMI), combined with familial, behavioral, and nutritional factors in the northeast of Mexico. MATERIAL AND METHODS: This is a case control study of patients less than 47 years of age with no personal history of angina, AMI, or cerebrovascular disease. Cases corresponded to patients with AMI (incident and primary cases; n = 55) and controls were blood donors located at the same hospital (n = 55). Behavioral, nutritional, and cardiometabolic risk factors were measured. Multivariate logistic regression was used for estimating odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: MS increased the risk for premature AMI (95% CI: 1.73-39.5) eightfold, followed by smoking (OR: 7.76; 95% CI: 1.27-47.3), family history of AMI or sudden death (OR: 11.0; 95% CI: 2.03-60.4), and sedentary lifestyle (OR: 2.26; 95% CI: 2.52-9.80), independent of potential confounders. CONCLUSIONS: The study highlights the magnitude of the risk of MS for AMI in Mexican young adults. The phenomenon of coronary diseases among young adults needs essential attention from the health sector.

Surgical experience in cardiac myxomas at a tertiary hospital.

INTRODUCTION: Cardiac myxomas account for 50% of all benign cardiac tumors. Their clinical presentation varies from embolisms to fever. Our objective was to describe the surgical experience in the resection of cardiac myxomas during an 8-year period. METHODS: This is a retrospective, descriptive study of a series of cases with cardiac myxomas diagnosed from 2014 to 2022 at a tertiary care center. Descriptive statistics were used to define the populational and surgical characteristics. We used Pearson's correlation to study the relationship between postoperative complications and age, tumor size and affected cardiac chamber. RESULTS: 31 patients were included, with a predominance of females (1:2 ratio). The prevalence was 0.44%, which was calculated based on the number of cardiac surgeries performed in our unit over the 8-year period. The main clinical manifestation was dyspnea (85%, n = 23), followed by cerebrovascular event (CVE) (18%, n = 5). Atriotomy and resection of the pedicle were performed with preservation of the interatrial septum. Mortality was 3.2%. The postoperative evolution was uneventful in 77%. Tumor recurrence occurred in 2 patients (7%), both debuting with embolic phenomena. No association was observed between postoperative complications or recurrence and tumor size, nor aortic clamping and extracorporeal circulation times with regard to age. CONCLUSIONS: Four atrial myxoma resections are performed in our unit per year, with an estimated prevalence of 0.44%. The tumor characteristics described coincide with the previous literature. A relationship between embolisms and recurrences cannot be ruled out. Wide surgical resection of the pedicle and base of tumor implantation may influence tumor recurrence, although further studies are needed.

[Educational intervention on organ and tissue donation at UMAE No. 34]. / Intervención educativa sobre donación de órganos y tejidos en la UMAE No. 34.

Background: The lack of information associated with donation is devastating for those patients in need of a transplant and requires a solution based on changing social perception through educational interventions. Objective: Determine the level of knowledge of the general population after an educational intervention about organ and tissue donation at the Hospital de Cardiología UMAE No. 34. Methods: Educational intervention study with measurement before and after, prospective. Instrument validated using the Kuder-Richardson formula with a reliability coefficient of 0.74. The study population was made up of the general population in the waiting rooms at UMAE No. 34, only the associations with values of p < 0.05 were considered statistically significant. Results: 266 evaluation instruments were applied to 133 participants. The educational intervention contributed to an increase in the level of knowledge (p = 0.0001). The level of knowledge after the intervention was higher in the younger participants (p = 0.013) and in those with a university studies (p = 0.0001). The relation between age and the level of subsequent knowledge showed favorable significance in the intention to donate in younger participants with high subsequent knowledge (p = 0.046). Conclusions: An educational intervention on donation of organs and tissues for transplant purposes is an effective strategy to increase and reinforce the knowledge of the general population.

Introducción: la falta de información relacionada con la donación de órganos y tejidos resulta devastadora para aquellos pacientes en necesidad de un trasplante, y requiere de una solución basada en el cambio de percepción social mediante intervenciones educativas. Objetivo: determinar el nivel de conocimiento de la población general posterior a una intervención educativa sobre la donación de órganos y tejidos en el Hospital de Cardiología No. 34. Métodos: estudio de intervención educativa con medición antes y después, prospectivo. Instrumento validado mediante fórmula de Kuder-Richardson con coeficiente de fiabilidad de 0.74. La población de estudio se conformó por la población general en las salas de espera de la UMAE No. 34. Las asociaciones con valores de p < 0.05 se consideraron estadísticamente significativas. Resultados: se aplicaron 266 instrumentos de evaluación en 133 participantes. La intervención educativa contribuyó a aumentar el nivel de conocimiento (p = 0.0001). El nivel de conocimiento posterior a la intervención fue mayor en los participantes jóvenes (p = 0.013) y en aquellos con estudios universitarios (p = 0.0001). La relación entre la edad y el nivel de conocimiento posterior mostró significancia favorable en la intención de donación en jóvenes con conocimiento posterior alto (p = 0.046). Conclusiones: una intervención educativa sobre la donación de órganos y tejidos con fines de trasplantes es una estrategia eficaz para aumentar y reforzar el conocimiento de la población general.

Frank's sign associated with the severity of ischemic heart disease in patients under 65 years old.

BACKGROUND AND OBJECTIVE: Frank's sign is the diagonal ear fold which has been associated with ischemic heart disease. The objective of this work was to evaluate the relationship of Frank's sign with severity of ischemic heart disease in adults ≤ 65 years old in the northeast of Mexico. PATIENTS AND METHODS: A cross-sectional study was conducted in patients ≤ 65 years old who underwent coronary angiography consecutively over a period of 5 months in 2022. Severe coronary artery disease (CAD) was associated with Frank's sign and other common cardiovascular risks. To determine the association, bivariate and multivariate analysis was performed using logistic regression that included variables with a value of p<0.05. Statistical analysis was performed with SPSS version 22. RESULTS: We included 311 patients ≤ 65 years, of whom 80% were men. The median age was 57 years (range 28-65). Frank's sign was positive in 62% of the population. The main clinical characteristics in patients with Frank's sign were type 2 diabetes mellitus (55%), p=0.003, dyslipidemia (53%), p=0.026 and smoking (68%), p=0.002. In the multivariate analysis, the independent variables associated with severe CAD were Frank's Sign OR 3.26; 95% CI (1.98-5.38), p≤0.001, male gender OR 2.28; 95% CI (1.20-4.35), p=0.012, and dyslipidemia OR 1.81; 95% CI (1.11-2.97), p=0.017. CONCLUSIONS: There is an independent association between Frank's sign with the presence of severe CAD in patients ≤ 65 years old, which may be useful for screening and prevention.

Breast Cancer Tissue Explants: An Approach to Develop Personalized Therapy in Public Health Services.

Breast cancer is one of the main causes of death worldwide. Lately, there is great interest in developing methods that assess individual sensitivity and/or resistance of tumors to antineoplastics to provide personalized therapy for patients. In this study we used organotypic culture of human breast tumor slices to predict the experimental effect of antineoplastics on the viability of tumoral tissue. Samples of breast tumor were taken from 27 patients with clinically advanced breast cancer; slices were obtained and incubated separately for 48 h with paclitaxel, docetaxel, epirubicin, 5-fluorouracil, cyclophosphamide, and cell culture media (control). We determined an experimental tumor sensitivity/resistance (S/R) profile by evaluating tissue viability using the Alamar Blue® metabolic test, and by structural viability (histopathological analyses, necrosis, and inflammation). These parameters were related to immunohistochemical expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The predominant histological type found was infiltrating ductal carcinoma (85.2%), followed by lobular carcinoma (7.4%) and mixed carcinoma (7.4%). Experimental drug resistance was related to positive hormone receptor status in 83% of samples treated with cyclophosphamide (p = 0.027). Results suggest that the tumor S/R profile can help to predict personalized therapy or optimize chemotherapeutic treatments in breast cancer.

Class 1 integrons in clinical and swine industry isolates of Salmonella Typhimurium from Colombia, dating 1997 to 2017.

Background. Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) has been linked to outbreaks of foodborne gastroenteritis disease, and the emergence of antimicrobial-resistant clones. In Colombia, laboratory surveillance of Salmonella spp. between 1997-2018 revealed that S. Typhimurium was the most ubiquitous serovar (27.6 % of all Salmonella isolates), with increasing levels of resistance to several families of antibiotics.Hypothesis. Resistant isolates of S. Typhimurium recovered from human clinical, food and swine samples carry class 1 integrons that are linked to antimicrobial resistance genes.Aim. Identify class 1 integrons, and investigate their association with other mobile genetic elements, and their relationship to the antimicrobial resistance of Colombian S. Typhimurium isolates.Methods. In this study, 442 isolates of S. Typhimurium were analysed, of which 237 were obtained from blood culture, 151 from other clinical sources, 4 from non-clinical sources and 50 from swine samples. Class 1 integrons and plasmid incompatibility groups were analysed by PCR and whole-genome sequencing (WGS), and regions flanking integrons were identified by WGS. The phylogenetic relationship was established by multilocus sequence typing (MLST) and single-nucleotide polymorphism (SNP) distances for 30 clinical isolates.Results . Overall, 39 % (153/392) of the human clinical isolates and 22 % (11/50) of the swine S. Typhimurium isolates carried complete class 1 integrons. Twelve types of gene cassette arrays were identified, including dfr7-aac-bla OXA-2 (Int1-Col1), which was the most common one in human clinical isolates (75.2 %, 115/153). Human clinical and swine isolates that carried class 1 integrons were resistant to up to five and up to three antimicrobial families, respectively. The Int1-Col1 integron was most prevalent in stool isolates and was associated with Tn21. The most common plasmid incompatibility group was IncA/C.Conclusions. The widespread presence of the IntI1-Col1 integron in Colombia since 1997 was striking. A possible relationship between integrons, source and mobile elements that favour the spread of antimicrobial resistance determinants in Colombian S. Typhimurium was identified.

Induction of virulence factors, apoptosis, and cytokines in precision-cut hamster liver slices infected with Entamoeba histolytica.

Precision-cut liver slices (PCLS) are mainly used to evaluate hepatotoxicity and metabolism of chemicals, as well as to study mechanisms of liver damage and repair. However, recently they have been used as a system to study amoebic infections. The aim of this study was to validate this model as an alternative for experimental amoebic liver absess (ALA) in animals. To do this, the PCLS was analyzed for the expression of amoebapore and cysteine proteinases 1 and 5, three of the most studied virulence factors of Entamoeba histolytica, as well as the induction of apoptosis and cytokines production in response to the ex vivo infection. PCHLS were prepared with the Brendel-Vitron tissue slicer and then, infected with 200,000 trophozoites of E. histolytica. Samples were taken at 0, 6, 12, 18, and 24 h and compared to control non-infected slices. Morphological studies were performed in order to verify the infection; while apoptosis was studied by TUNEL and PAS techniques. The expression of cysteine proteinases (1 and 5), and amoebapore, was analyzed by real-time PCR. By using ELISA assays, the production of cytokines was also studied. PCHLS were found to be a reproducible infection system, and E. histolytica caused the expression of cysteine proteinases and amoebapore in infected slices. At the same time, trophozoites induce release of cytokines and apoptotic death of the hepatocytes close to them. PCHLS represent a new and suitable alternative model to study the pathogenesis of hepatic amoebiasis.

Metabolites and metabolic pathways associated with rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases that result from the combined influence of genetic and environmental factors that promotes the loss of tolerance to cellular components. The complexity of these diseases converts them into a major challenge at the diagnostic and treatment level. Therefore, it is convenient to implement the use of tools for a better understanding of the physiopathology of these diseases to propose reliable biomarkers. The "omics" disciplines like metabolomics and lipidomics allow to study RA and SLE in a higher degree of detail since they evaluate the metabolites and metabolic pathways involved in disease pathogenesis. This review has compiled the information of metabolomics and lipidomics studies where samples obtained from RA and SLE patients were evaluated to find the metabolites and pathways differences between patients and healthy controls. In both diseases, there is a decrease in several amino acids and oxidative stress-related metabolites like glutathione. These findings may be useful for functional metabolomics studies aiming to reprogram the metabolism in a disease setting to recover normal immune cell homeostasis and function.

[Donation in the Cardiology Hospital No. 34]. / Donación en el Hospital de Cardiología No. 34.

BACKGROUND: Chronic degenerative diseases have become a challenge for the Mexican health system. Faced with this problem, health institutions have focused on the therapeutic potential of organ and tissue donation and transplantation. OBJECTIVE: To analyze the experience of the donation program and to identify areas of opportunity at the Hospital de Cardiología No. 34 (Hospital of Cardiology Number 34), in Monterrey, Nuevo León, Mexico. MATERIAL AND METHODS: Observational, cross-sectional, and retrospective study. The study population was made up by deaths and successful interviews. Only groupings with values of p < 0.05 were considered statistically significant. RESULTS: A global of 1947 deaths were registered and a total of 210 interviews were carried out; 83 (39.5%) family members accepted to donate and 127 (60.5%) refused to donate. Only 3 associations between variables had significant statistical value. The year was an important determinant in the increase in effective donations (p = 0.010), and so was the month of the year (p = 0.037), obtaining more positive interviews in the second half of the year; finally, the shift also contributed to the family response (p = 0.012), with the morning shift being the best shift to conduct a successful family interview. CONCLUSIONS: It is imperative to conduct studies that analyze and describe the experience of donation programs to promote and encourage the value of donation.

INTRODUCCIÓN: las enfermedades crónico-degenerativas se han convertido en un desafío para el sistema de salud mexicano. Frente a este problema, las instituciones sanitarias se han enfocado en el potencial terapéutico de la donación y el trasplante de órganos y tejidos. OBJETIVO: analizar la experiencia del programa de donación e identificar áreas de oportunidad en el Hospital de Cardiología No. 34, en Monterrey, Nuevo León, México. MATERIAL Y MÉTODOS: estudio observacional, transversal y retrospectivo. La población de estudio se conformó por defunciones y entrevistas exitosas. Únicamente agrupaciones con valores de p < 0.05 se consideraron estadísticamente significativas. RESULTADOS: se registró un global de 1947 defunciones y se efectuaron en total 210 entrevistas; 83 (39.5%) disponentes secundarios aceptaron donar y 127 (60.5%) se negaron. Solo tres asociaciones entre variables tuvieron valor estadístico significativo. El año fue un determinante importante en el incremento de las donaciones efectivas (p = 0.010) y también lo fue el mes del año (p = 0.037), pues se obtuvieron más entrevistas positivas en el segundo semestre del año; finalmente, el turno también contribuyó en la respuesta familiar (p = 0.012) y fue el turno matutino el mejor para hacer una entrevista familiar exitosa. CONCLUSIONES: es imperativo llevar a cabo estudios que analicen y describan la experiencia del programa de donación para promover y fomentar el valor de la donación.

Treatment-free remission in patients with chronic myeloid leukemia: recommendations of the LALNET expert panel.

Tyrosine kinase inhibitors (TKIs) have dramatically changed the survival of chronic myeloid leukemia (CML) patients, and treatment-free remission (TFR) has recently emerged as a new goal of CML treatment. The aim of this work was to develop recommendations for TKI discontinuation in Latin America (LA), outside of clinical trials. A working group of CML experts from LA discussed 22 questions regarding TFR and reached a consensus for TFR recommendations in the region. TFR is indicated in patients in first chronic phase, with typical BCR-ABL transcripts, under TKI treatment of a minimum of 5 years, in sustained deep molecular response (DMR; molecular response 4.5 [MR4.5]) for 2 years. Sustained DMR must be demonstrated on at least 4 international reporting scale quantitative polymerase chain reaction (PCR) tests, separated by at least 3 months, in the immediate prior 2 years. After second-line therapy, TFR is indicated in previously intolerant, not resistant, patients. Molecular monitoring is recommended monthly for the first 6 months, every 2 to 3 months from months 7 to 12, and every 3 months during the second year, indefinitely. Treatment should be reintroduced if major molecular response is lost. Monitoring of withdrawal syndrome, glucose levels, and lipid profile is recommended after discontinuation. After TKI reintroduction, molecular monitoring is indicated every 2 to 3 months until MR4.0 achievement; later, every 3 to 6 months. For the TFR attempt, having standardized and reliable BCR-ABL PCR tests is mandatory. These recommendations will be useful for safe discontinuation in daily practice and will benefit patients who wish to stop treatment in emergent regions, in particular, with TKI-related chronic adverse events.

Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure.

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/mL) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0-F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1-F3), and a decrease in the quality of sperm (F0-F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.