Pautas de manejo de trombosis venosa en miembros inferiores según la sociedad europea de cirugía vascular 2021.

Deep vein thrombosis (DVT) is caused by a fibrin thrombus which reduces the blood supply to the surrounding tissues. Within the complications reported in the literature we find pulmonary embolic events (PE), which, once generated, develop great repercussions on the survival of those who suffer from them. The diagnosis is made in a multidisciplinary manner, using measures such as the Wells score, D-dimer measurement, computed venography, among others. The European Society of Vascular Surgery in its 2021 clinical practice guideline, mentions the appropriate way to make the diagnosis, taking into account the risk factors, the classification according to the triggering factor and the currently available images. Likewise, it indicates the treatment that should be offered based on the location of the thrombus and what pharmacological and non-pharmacological measures can be chosen in different clinical scenarios. The following review highlights the key and most relevant aspects to take into account for the management of patients with this entity.La trombosis venosa profunda (TVP), es provocada por un trombo de fibrina el cual reduce el aporte sanguíneo a los tejidos circundantes. Dentro de las complicaciones reportadas en la literatura encontramos eventos embólicos pulmonares (EP), los cuales, una vez generados, desarrollan  grandes repercusiones en la sobrevida de quien las padece. El diagnóstico se realiza de manera multidisciplinaria, utilizando medidas como el puntaje de Wells, medición de dímero D, venografía computarizada entre otros. La  Sociedad Europea de Cirugía vascular en su guía de práctica clínica 2021, nos menciona la manera adecuada de realizar el diagnóstico, teniendo en cuenta los factores de riesgo,  la clasificación según el factor desencadenante y las imágenes actualmente disponibles. Así mismo nos indica el tratamiento que se debe ofrecer en base a la localización del trombo y que medidas farmacológicas y no farmacológicas se pueden optar en diferentes escenarios clínicos. En la siguiente revisión se destacan los aspectos claves y más relevantes a tener en cuenta para el manejo de los pacientes con esta entidad

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry

Stroke; Thrombectomy; PrognosisIctus; Trombectomia; PronòsticIctus; Trombectomía; PronósticoBackground and purpose: In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. Methods: Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score 3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). Results: Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). Conclusions: Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors

Body mass index, performance on activities of daily living and cognition: analysis in two different populations

Background With this study, we aim to determine the associations of the different categories of the body mass index (BMI) with activities of daily living (ADL) and cognitive performance in two different populations living in the community; Colombian and South Korean older adults. Methods We performed a cross-sectional analysis of two surveys separately; The Survey on Health, Well-Being, and Aging in Colombia (SABE) (n = 23,343) and the Korean Longitudinal Study of aging (KLoSA) (n = 4556). Participants older than 50 years were selected from rural and urban areas achieving a representative sample. Here we investigated the association between BMI categories with function using zero-inflated negative binomial regressions, and with cognition using logistic regression models. Results After adjustment, in Colombia, underweight was associated with an impaired score on the Mini-mental State Examination (MMSE) and worse performance in the instrumental activities of daily living (IADL). Also, being overweight was associated with a better score on the MMSE and the IADL. For both outcomes education level significantly influenced the predictions. In South Korea, there were no significant associations for cognition, IADL, or basic activities of daily living (BADL). Conclusions In the Colombian population, underweight, was associated with reduced cognitive performance and daily functioning. Additionally, being overweight but not obese was associated with better cognition and daily functioning. In South Korea, there were no significant associations between BMI and cognition, IADL, or BADL.publishedVersio

Dosis letal media para inducir mutaciones, con rayos gamma, en pasto janeiro (Eriochloa polystachya Kunth)

Antecedentes: Los rayos gamma se pueden utilizar para el mejoramiento genético de las plantas y generar mutaciones que puedan ser útiles. La investigación se realizó con el objetivo de determinar la dosis letal media (DL50) para inducir mutaciones, con radiación gamma, en pasto janeiro (Eriochloa polystachya Kunth). Métodos: Se irradiaron 8 600 estolones de 8 cm de largo con un nudo, cortados de plantas maduras de más de seis meses de edad con dosis de 0; 25; 50; 75 y 100 Gray de rayos gamma Co60. Se evaluó el porcentaje de establecimiento, altura de planta y mortalidad de los estolones. Los datos fueron analizados a través del análisis de regresión lineal probabilística. Resultados: De acuerdo con la variable porcentaje de establecimiento, la DL50, es igual a 52,60 Gy para el genotipo estudiado, con R2 de 57,73. Conclusiones: Se concluye que la dosis media letal para inducir mutaciones en el pasto Janeiro (Eriochloa polystachya Kunth) se obtuvo con 52,60 Gy con R2 de 57,73

The insecticides permethrin and chlorpyrifos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells

Altres ajuts: European Food and Safety Authority, EFSA.PRAS.2018.04-CT1; Consejo Nacional de Ciencia y Tecnología, CB-2012-01-183467; Centro de Investigación Biomédica en Red en Cáncer, PID2019-104695RBI00; Asociación Española Contra el Cáncer, AECC INVES211226MOLI

Hematopoiesis under telomere attrition at the single-cell resolution

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA, overcomes interferon signaling activation in telomere-dysfunctional hematopoietic stem cells and these cells’ skewed differentiation towards the megakaryocytic lineage. This study challenges the historical hypothesis that telomere attrition limits the proliferative potential of hematopoietic stem cells by inducing apoptosis, autophagy, or senescence, and suggests that targeting IFI16 signaling axis might prevent hematopoietic stem cell functional decline in conditions affecting telomere maintenance

Parenteral Nutrition: Current Use, Complications, and Nutrition Delivery in Critically Ill Patients

Background: Parenteral nutrition (PN) is needed to avoid the development of malnutrition when enteral nutrition (EN) is not possible. Our main aim was to assess the current use, complications, and nutrition delivery associated with PN administration in adult critically ill patients, especially when used early and as the initial route. We also assessed the differences between patients who received only PN and those in whom EN was initiated after PN (PN-EN). Methods: A multicenter (n = 37) prospective observational study was performed. Patient clinical characteristics, outcomes, and nutrition-related variables were recorded. Statistical differences between subgroups were analyzed accordingly. Results: From the entire population (n = 629), 186 (29.6%) patients received PN as initial nutrition therapy. Of these, 74 patients (11.7%) also received EN during their ICU stay (i.e., PNEN subgroup). PN was administered early (<48 h) in the majority of patients (75.3%; n = 140) and the mean caloric (19.94 +/- 6.72 Kcal/kg/day) and protein (1.01 +/- 0.41 g/kg/day) delivery was similar to other contemporary studies. PN showed similar nutritional delivery when compared with the enteral route. No significant complications were associated with the use of PN. Thirty-two patients (43.3%) presented with EN-related complications in the PN-EN subgroup but received a higher mean protein delivery (0.95 +/- 0.43 vs 1.17 +/- 0.36 g/kg/day; p = 0.03) compared with PN alone. Once adjusted for confounding factors, patients who received PN alone had a lower mean protein intake (hazard ratio (HR): 0.29; 95% confidence interval (CI): 0.18-0.47; p = 0.001), shorter ICU stay (HR: 0.96; 95% CI: 0.91-0.99; p = 0.008), and fewer days on mechanical ventilation (HR: 0.85; 95% CI: 0.81-0.89; p = 0.001) compared with the PN-EN subgroup. Conclusion: The parenteral route may be safe, even when administered early, and may provide adequate nutrition delivery. Additional EN, when possible, may optimize protein requirements, especially in more severe patients who received initial PN and are expected to have longer ICU stays. NCT Registry: 03634943

Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1 Mutant Myelodysplastic Syndromes With Ringed Sideroblasts

View full abstracthttps://openworks.mdanderson.org/leading-edge/1025/thumbnail.jp

Targeting DNA2 Overcomes Metabolic Reprogramming in Multiple Myeloma

DNA damage resistance is a major barrier to effective DNA-damaging therapy in multiple myeloma (MM). To discover mechanisms through which MM cells overcome DNA damage, we investigate how MM cells become resistant to antisense oligonucleotide (ASO) therapy targeting Interleukin enhancer binding factor 2 (ILF2), a DNA damage regulator that is overexpressed in 70% of MM patients whose disease has progressed after standard therapies have failed. Here, we show that MM cells undergo adaptive metabolic rewiring to restore energy balance and promote survival in response to DNA damage activation. Using a CRISPR/Cas9 screening strategy, we identify the mitochondrial DNA repair protein DNA2, whose loss of function suppresses MM cells\u27 ability to overcome ILF2 ASO-induced DNA damage, as being essential to counteracting oxidative DNA damage. Our study reveals a mechanism of vulnerability of MM cells that have an increased demand for mitochondrial metabolism upon DNA damage activation

Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy

Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found that MDS HSCs in two distinct differentiation states are maintained throughout the clinical course of the disease, and expand at progression, depending on recurrent activation of the anti-apoptotic regulator BCL-2 or nuclear factor-kappa B-mediated survival pathways. Pharmacologically inhibiting these pathways depleted MDS HSCs and reduced tumor burden in experimental systems. Further, patients with MDS who progressed after failure to frontline HMA therapy and whose HSCs upregulated BCL-2 achieved improved clinical responses to venetoclax-based therapy in the clinical setting. Overall, our study uncovers that HSC architectures in MDS are potential predictive biomarkers to guide second-line treatments after HMA failure. These findings warrant further investigation of HSC-specific survival pathways to identify new therapeutic targets of clinical potential in MDS