Cytogenomic characterization of small supernumerary marker chromosomes in patients with pigmentary mosaicism.

Introduction: The combination of gene content on the marker chromosome, chromosomal origin, level of mosaicism, origin mechanism (chromothripsis), and uniparental disomy can influence the final characterization of sSMCs. Several chromosomal aberrations, including sSMCs, have been observed in 30%-60% of patients with pigmentary mosaicism, and in more than 80%, chromosomal abnormalities are present in the mosaic state. In patients with pigmentary mosaicism the most representative chromosomes involved in sSMCs are 3, 5, 6, 9, 10, 13, 15, 18, 20, and X. In this study, we included the complete clinical, cytogenetic, and molecular characterization of seven patients with pigmentary mosaicism associated with the presence of SMCs of different chromosomal origins. Methods: The patients were diagnosed by the Genetics and Dermatology Department of three different hospitals. Cytogenetic and FISH analyses were performed on peripheral blood, light skin, and dark skin. FISH analysis was performed using different probes, depending on the marker chromosome description. Different array analysis was performed. Results: To date, of the seven cases studied, the chromosomal origins of six were successfully identified by FISH or array analysis. The chromosomes involved in SMCs were 6, 9, 15, and 18, X. The most frequently found was the centric minute structure. Discussion: To date, this group of seven patients constitutes the largest clinical and cytogenetically finely described study of cases with pigmentary mosaicism associated with sSMCs. Undoubtedly, analysis of the two skin types is a fundamental part of our study, as numerical differences may occur in the cell lines found in each skin type. The knowledge generated in this study will help delineate a very heterogeneous entity more accurately, and in the future, analyzing more patients with PM will likely establish a more definite association with the presence of this genetic alteration.

Timing of previous heart failure hospitalization as a prognostic factor for emergency department heart failure patients.

To investigate whether the timing of a previous hospital admission for acute heart failure (AHF) is a prognostic factor for AHF patients revisiting the emergency department (ED) in the subsequent 12-month follow-up. All ED AHF patients enrolled in the previously described EAHFE registry were stratified by the presence or absence of an AHF hospitalization admission in the prior 12 months. The primary outcome was 12-month all-cause mortality post ED visit. Secondary end points were hospital admission, prolonged hospitalization (> 7 days), mortality during hospitalization and a 90-day post-discharge adverse composite event (ACE) rate, defined as ED revisits due to AHF, hospitalizations due to AHF, or all-cause mortality. Outcomes were adjusted for baseline and AHF episode characteristics.Of 5,757 patients included, the median age was 84 years (IQR 77-88); 57% were women, and 3,759 (65.3%) had an AHF hospitalization in the previous 12 months. The 12-month mortality was 37% (41.7% vs. 28.3% p < 0.001), hospital admission was 76.1% (78.8% vs. 71.1% p < 0.001) ACE was 60.2% (65.1% vs. 50.5% p < 0.001). In the adjusted analysis, patients with AHF hospitalization in the prior 12 months had a higher mortality (HR = 1.41; 95% CI 1.27-1.56), 90-day ACE rate (HR = 1.45: 95% CI 1.32-1.59), and more hospital admissions (OR = 1.32; 95% CI 1.16-1.51), with shorter times since the previous hospitalization being related to the outcomes analyzed. One-year mortality, adverse events at 90 days, and readmission rates are increased in ED AHF patients previously admitted within the last 12 months.

Carriage of multidrug-resistant Gram-negative bacilli: duration and risk factors.

Identification of risk factors influencing the duration of carriage of multidrug-resistant Gram-negative bacilli (MDR-GNB) may be useful for infection control. The aim of this study is to estimate the impact of several factors collected for routine hospital surveillance on the duration of carriage of selected MDR-GNB. From January 2015 to July 2021, patients with at least two clinical/surveillance samples positive for MDR-GNB different from ESBL-producing E. coli or AmpC - exclusively producing Enterobacterales were assessed. Microorganisms, age, number of admissions, clinical or rectal sample, sex, and admission service were evaluated as risk factors. Multivariate analysis was performed by a Cox proportional hazard model. A total of 1981 episodes of colonization were included. Involved microorganisms were ESBL-Klebsiella pneumoniae (KP) in 1057 cases (53.4%), other ESBL-non-E. coli Enterobacterales in 91 (4.6%), OXA-48-KP in 263 (13.3%), KPC-KP in 90 (4.5%), VIM-KP in 29 (1.5%), carbapenemase-producing non-KP Enterobacterales (CP-non-KP) in 124 (6.3%), and MDR Pseudomonas aeruginosa (MDR-PAER) in 327 (16.5%). No differences in duration of colonization were observed among ESBL-KP (median colonization time 320 days), ESBL-non-E. coli Enterobacterales (226 days), OXA48-KP (305 days), and MDR-PAER (321 days). For each group, duration of colonization was significantly longer than that of KPC-KP (median colonization time 60 days), VIM-KP (138 days), and CP-non-KP (71 days). Male sex (HR = 0.88; 95% CI 0.78-0.99), detection in Hepatology-Gastroenterology (HR = 0.71; 95% CI 0.54-0.93), clinical sample (HR = 0.61; 95% CI 0.53-0.69), and > 2 admissions after first detection (HR = 0.47; 95% CI 0.42-0.52) were independent predictors of longer carriage, whereas VIM-KP (HR = 1.61; 95% CI 1.04-2.48), KPC-KP (HR = 1.85; 95% CI 1.49-2.3), and CP-non-KP (HR = 1.92; 95% CI 1.49-2.47) were associated with shorter colonization time. Duration of colonization was significantly longer for ESBL-KP, other ESBL-non-E. coli Enterobacterales, OXA-48-KP, and MDR-PAER. For these microorganisms, prolonging surveillance up to 2.5-3 years should be considered. Male sex, clinical sample, multiple readmissions, admission service, and type of microorganism are independent predictors of the duration of carriage.

Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Biochemical and Hematological Relationship with the Evaluation of Autonomic Dysfunction by Heart Rate Recovery in Patients with Asthma and Type 2 Diabetes.

There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation (p < 0.01). Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.

Echocardiography and FDG-PET/CT scan in Gram-negative bacteremia and cardiovascular infections.

PURPOSE OF REVIEW: Current evidence on cardiovascular infections in Gram-negative blood stream infections (GNBSI) with focus on the use of transesophageal echocardiography (TEE) and 18F-Fluorodeoxyglucose - positron emission tomography/Computed tomography (FDG-PET/CT) in the diagnostic workup. RECENT FINDINGS: Most evidence focuses on characteristics of diagnosed cardiovascular infections and the proportion caused by GNBSI. These proportions are low (1-5%) when it comes to native and prosthetic valve endocarditis as well as cardiac implantable electronic device (CIED) infections whereas the proportion of vascular graft infections caused by GNBSI seems substantially higher (30-40%). Information on the prevalence of cardiovascular infection in patients with GNBSI is limited to a few studies finding around 3% endocarditis in patients with GNBSI and a prosthetic heart valve and 4-16% device-related infection in patients with CIED and GNBSI. SUMMARY: Patients with GNBSI and native or prosthetic valves should only undergo work-up for endocarditis (TEE and FDG-PET/CT) if they present GNBSI relapse or signs suggestive of endocarditis. CIED patients with GNBSI with Pseudomonas or Serratia spp. should undergo TEE and PET/CT because of the high prevalence of device-related infection. In other GNBs without IE suggestive signs, normal BSI treatment is reasonable and only cases with relapse need work-up. GNBSI in patients with vascular grafts should lead to consideration of PET/CT.

Experience with the use of siltuximab in patients with SARS-CoV-2 infection.

OBJECTIVE: The study aims to describe characteristics and clinical outcome of patients with SARS-CoV-2 infection that received siltuximab according to a protocol that aimed to early block the activity of IL-6 to avoid the progression of the inflammatory flare. METHODS: Retrospective review of the first 31 patients with SARS-CoV-2 treated with siltuximab, in Hospital Clinic of Barcelona or Hospital Universitario Salamanca, from March to April 2020 with positive polymerase-chain reaction (PCR) from a nasopharyngeal swab. RESULTS: The cohort included 31 cases that received siltuximab with a median (IQR) age of 62 (56-71) and 71% were males. The most frequent comorbidity was hypertension (48%). The median dose of siltuximab was 800 mg ranging between 785 and 900 mg. 7 patients received siltuximab as a salvage therapy after one dose of tocilizumab. At the end of the study, a total of 26 (83.9) patients had been discharged alive and the mortality rate was 16.1% but only 1 out of 24 that received siltuximab as a first line option (4%). CONCLUSIONS: Siltuximab is a well-tolerated alternative to tocilizumab when administered as a first line option in patients with COVID-19 pneumonia within the first 10 days from symptoms onset and high C-reactive protein.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Real-life use of remdesivir in hospitalized patients with COVID-19.

OBJECTIVE: Controversial results on remdesivir efficacy have been reported. We aimed to report our real-life experience with the use of remdesivir from its availability in Spain. METHODS: We performed a descriptive study of all patients admitted for ≥48 hours with confirmed COVID-19 who received remdesivir between the 1st of July and the 30th of September 2020. RESULTS: A total of 123 patients out of 242 admitted with COVID-19 at our hospital (50.8%) received remdesivir. Median age was 58 years, 61% were males and 56.9 % received at least one anti-inflammatory treatment. No adverse events requiring remdesivir discontinuation were reported. The need of intensive care unit admission, mechanical ventilation and 30-days mortality were 19.5%, 7.3% and 4.1%, respectively. CONCLUSIONS: In our real-life experience, the use of remdesivir in hospitalized patients with COVID-19 was associated with a low mortality rate and good safety profile.

Resultados del primer registro nacional de fibrosis pulmonar idiopática en Chile / Results of the first national register of idiopathic pulmonary fibrosis in Chile

INTRODUCCIÓN: La FPI es la neumonía intersticial idiopática más común, con cifras de incidencia y prevalencia que varían en el mundo por la poco uniforme manera de recolectar casos en los diferentes estudios. No hay cifras publicadas sobre la epidemiología de la FPI en Chile ni Latinoamérica. Se hace relevante conocerlas por la carga sanitaria que representan los pacientes con FPI y por la aprobación reciente de drogas antifibróticas de alto costo. El objetivo de este estudio fue realizar un registro de pacientes con FPI atendidos por neumólogos chilenos de diversos regiones del país, con los medios diagnósticos que habitualmente utilizan en la vida real. PACIENTES Y MÉTODOS: Se utilizó una encuesta electrónica en línea diseñada por el grupo de enfermedades pulmonares difusas del Instituto Nacional del Tórax para registro de pacientes con diagnóstico de FPI según criterios ATS/ERS/JRS/ALAT desde junio de 2015 a junio de 2017. RESULTADOS: 40 de los 200 neumólogos invitados enviaron casos de FPI de las 13 regiones del país, completando un total de 700 pacientes. 2/3 eran casos antiguos, un número similar de hombres y mujeres, 73% tienen patrón definitivo de UIP (Usual Interstitial Pneumonia) en tomografía axial computarizada, la mayoría eran pacientes sobre 60 años y en solo 16% se solicitó biopsia para diagnóstico. CONCLUSIONES: Un registro de 700 casos representa un número muy importante de pacientes con FPI en Chile que nos permite acercarnos a la caracterización de la cohorte y a fortalecer una red de especialistas dedicados al cuidado de estos pacientes y sus familias.

INTRODUCTION: Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia, with incidence and prevalence figures varying worldwide because of the inconsistent way of collecting cases in different studies. There are no published figures on the epidemiology of IPF in Chile or Latin America. It is relevant to know them because of the health burden of patients with IPF and the recent approval for treatment purposes of high cost antifibrotic drugs. The objective of this study was to develop a clinical registry of patients with IPF treated by Chilean pulmonologists from different regions of the country, using the diagnostic means they usually use in real life. PATIENTS AND METHODS: An online electronic survey was designed by the group of diffuse pulmonary diseases of the "Instituto Nacional del Tórax" to register patients with diagnosis of IPF from June 2015 to June 2017 according to ATS/ERS/JRS/ALAT criteria. RESULTS: 40 of the 200 invited pulmonologists sent IPF cases from the country's 13 regions, completing a total of 700 patients. 2/3 were old cases, a similar number of men and women, 73% had definitive UIP pattern in CT, the majority were patients over 60 years old and in only 16% biopsy was requested for diagnosis. CONCLUSIONS: A register of 700 cases represents a very important number of patients with IPF in Chile that allows us to approach the characterization of the cohort and to strengthen a network of specialists dedicated to the care of these patients and their families.

Effect of Pleurotus agaves mushroom addition on the physicochemical and sensory properties of blue maize tortillas produced with traditional and ecological nixtamalization.

The physicochemical, nutritional and sensory properties of flours, doughs and tortillas made with traditional nixtamalization (TN) and ecological nixtamalization (EN) and enriched (9%) with the traditional maguey mushroom (Pleurotus agaves) were analysed. EN resulted in flours and tortillas having a greater content of bioactive compounds than that of TN flours, which represents a production process of maize tortillas containing high amounts of antioxidants. The addition of mushrooms to EN flours improved their sensory properties, whereas the addition of mushrooms to TN flours decreased them. The amount of P. agaves added to tortillas was equivalent to 3% enrichment with ß-glucans. The edible mushroom P. agaves, highly appreciated in many Mexican regions, improved the nutritional and sensory quality of blue maize tortillas when added to flours prepared by EN. A new product was developed using local traditional foods of complementary nutritional value.

COVID-19: from epidemiology to treatment.

The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.

Performance of differential time to positivity as a routine diagnostic test for catheter-related bloodstream infections: a single-centre experience.

OBJECTIVE: To assess the performance of differential time to positivity (DTP) for the diagnosis of catheter-related bloodstream infections (CRBSI). METHODS: From all episodes of bloodstream infections (BSI) diagnosed during a 15-year period (2003-17) those in which a paired set of blood cultures drawn from a catheter and a peripheral vein were positive for the same microorganism and had a clinically and/or microbiologically defined source were selected. To assess diagnostic discrimination ability and accuracy of DTP for CRBSI, area under the receiver operating characteristic curves (AUC) and performance characteristics of a DTP ≥2 h were computed. RESULTS: A total of 512 BSI were included, of which 302 (59%) were CRBSI. Discrimination ability of DTP was low for Staphylococcus aureus (AUC 0.656 ± 0.06), coagulase-negative staphylococci (AUC 0.618 ± 0.081), enterococci (AUC 0.554 ± 0.117) and non-AmpC-producing Enterobacteriaceae (AUC 0.653 ± 0.053); moderate for Pseudomonas aeruginosa (AUC 0.841 ± 0.073), and high for AmpC-producing Enterobacteriaceae (AUC 0.944 ± 0.039). For the entire sample, DTP had a low-to-moderate discrimination ability (AUC 0.698 ± 0.024). A DTP ≥2 h has a low sensitivity for coagulase-negative staphylococci (60%) and very low for S. aureus (34%), enterococci (40%) and non-AmpC-producing Enterobacteriaceae (42%). A DTP cut-off of 1 h improved sensitivity (90%) for AmpC-producing Enterobacteriaceae. CONCLUSIONS: Differential time to positivity performs well for diagnosing CRBSI only when AmpC-producing Enterobacteriaceae and P. aeruginosa are involved. Performance is low for common Gram-positive organisms and non-AmpC-producing enteric bacilli; a negative test should not be used to rule out CRBSI due to these microorganisms. A DTP ≥1 h may improve accuracy for AmpC-producing Enterobacteriaceae, particularly Enterobacter spp.

Low concentrations of permethrin and malathion induce numerical and structural abnormalities in KMT2A and IGH genes in vitro.

Pesticides are commonly used worldwide and almost every human is potentially exposed to these chemicals. Exposure to pesticides such as permethrin and malathion has been associated with hematological malignancies in epidemiological studies. However, biological evidence showing if these chemicals induce genetic aberrations involved in the etiology of leukemia and lymphoma is missing. In our previous work, we have shown that a single high exposure (200 µm, 24 hours) of permethrin and malathion induce damage in genes associated with hematological malignancies in peripheral blood mononuclear cells analyzed by interphase fluorescence in situ hybridization (FISH). In the present study, we assessed by FISH whether exposure to low concentrations (0.1 µm, 72 hours) of permethrin and malathion induce aberrations in KMT2A and IGH genes, which are involved in the etiology of leukemia and lymphoma. Peripheral blood mononuclear cells were exposed to the chemicals, and damage in these genes was assessed on interphases and metaphases. We observed that both chemicals at low concentration induced structural aberrations in KMT2A and IGH genes. A higher level of damage was observed in KMT2A gene with malathion treatment and in IGH gene with permethrin exposure. We also observed numerical aberrations induced by these chemicals. The most frequent aberrations detected on interphase FISH were also observed on metaphases. Our results show that permethrin and malathion induce genetic damage in genes associated with hematological cancer, at concentrations biologically relevant. In addition, damage was observed on dividing cells, which suggests that these cells maintain their proliferation capacity in spite of the genetic damage they possess.

Riesgo cardiovascular en una población adolescente de Timbío, Colombia / Cardiovascular risk in a teenage population in Timbío, Colombia

Resumen Introducción: Las enfermedades cardiovasculares se encuentran entre las primeras causas de muerte a nivel mundial y la evidencia científica sugiere que tienen un origen en edades tempranas, por lo que disminuir desde la adolescencia los riesgos que contribuyen a su aparición es indispensable. Objetivo: Determinar riesgo cardiovascular en la población adolescente de una institución educativa de Timbío, Cauca, 2015 - 2016. Metodología: Estudio cuantitativo, descriptivo, observacional y de corte transversal. Muestra: 100 estudiantes (47 mujeres, 53 hombres), de 10 a 19 años de edad. Se evaluaron variables sociodemográficas, antropométricas, fisiológicas, bioquímicas (glicemia), antecedentes personales, familiares, estilos de vida y uso de anticonceptivos orales. Resultados: Se encontró una mayor prevalencia de riesgo cardiovascular en el grupo etario adolescente (15-18 años) con 84.6%; el género femenino presentó más posibilidad de tener riesgo cardiovascular (OR: 2.8, IC 95% 1.17 - 6.87); el 7% afirmó consumir tabaco regularmente y el 12% son fumadores pasivos. Se obtuvo que el 26% ingiere bebidas alcohólicas, con una mayor prevalencia entre las edades de 15 a 18 años (OR: 19.4, IC 95% 2.45 - 48.11); en cuanto a la actividad física el 79% la practicaba de forma extracurricular. Presentar hábitos alimenticios no saludables genera mayor riesgo cardiovascular (OR: 5.57, IC 95% 1.95 - 15.90). El 67% (n= 67) tiene riesgo cardiovascular. Conclusiones: El género femenino, el grupo adolescente (15-18 años), el consumo de bebidas alcohólicas y hábitos alimenticios no saludables, se asocian con una mayor posibilidad de tener riesgo cardiovascular. Se encontró en un gran porcentaje de la población de estudio riesgo cardiovascular.

Abstract Introduction: Cardiovascular diseases are among the leading causes of death worldwide and scientific evidence suggests that they have an origin at early ages, so that diminishing from adolescence the risks that contribute to its emergence is essential. Objective: To determine cardiovascular risk in the adolescent population of a high school of Timbío, Cauca, 2015 - 2016. Methodology: Quantitative, descriptive, observational and cross-sectional study. Sample: 100 students (47 women, 53 men), from 10 to 19 years old. Sociodemographic, anthropometric, physiological, biochemical variables (glycemia), personal history, family history, lifestyles and use of oral contraceptives were evaluated. Results: A higher prevalence of cardiovascular risk was found in the adolescent age group (15-18 years) with 84.6%; female gender was more likely to have cardiovascular risk (OR: 2.8, 95% CI 1.17 - 6.87); 7% said they use tobacco regularly and 12% are passive smokers. It was obtained that 26% ingested alcoholic beverages, with a higher prevalence between the ages of 15 to 18 years (OR: 19.4, 95% CI 2.45-48.11); In terms of physical activity, 79% practiced it extracurricularly. Presenting unhealthy eating habits generates greater cardiovascular risk (OR: 5.57, 95% CI 1.95 - 15.90). 67% (n = 67) have cardiovascular risk. Conclusions: The female gender, the adolescent group (15-18 years), drink alcoholic beverages and unhealthy eating habits, are associated with a greater possibility of having cardiovascular risk. It was found in a large percentage of the study population cardiovascular risk.

"Exposure to the insecticides permethrin and malathion induces leukemia and lymphoma-associated gene aberrations in vitro".

Epidemiological studies have associated the exposure to permethrin and malathion with increased risk of leukemia and lymphoma. The aim of this study was to evaluate whether in vitro exposure to permethrin and malathion induces aberrations in genes involved in the etiology of these hematological malignancies. Genetic abnormalities in the IGH, KMT2A (MLL), ETV6 and RUNX1 genes, and aneuploidy induced by the in vitro exposure to permethrin and malathion (200µM, 24h), were analyzed by FISH in peripheral blood mononuclear cells (PBMCs). The gene fusions IGH-BCL2, KMT2A-AFF1 and ETV6-RUNX1 were further analyzed with nested RT-PCR in PBMCs, and in K562 cells exposed to acute and chronic treatments (0.1µM, 24h or every third day for two weeks) of insecticides. FISH analysis revealed that permethrin induces aneuploidy and structural alterations in IGH and KMT2A genes, and malathion induces breaks in KMT2A. RT-PCR detected ETV6-RUNX1 fusion in PBMCs acutely exposed to permethrin. Permethrin also induced ETV6-RUNX1 and IGH-BCL2 fusions in K562 cells, and malathion induced KMT2A-AFF1 and ETV6-RUNX1 fusions. Overall, we identified that both insecticides induce breaks and fusions in the studied genes, and permethrin induces aneuploidy. This study presents evidence of damage in cancer genes caused by these insecticides.