Oxydifficidin, a potent Neisseria gonorrhoeae antibiotic due to DedA assisted uptake and ribosomal protein RplL sensitivity.

Gonorrhea, which is caused by Neisseria gonorrhoeae, is the second most prevalent sexually transmitted infection worldwide. The increasing appearance of isolates that are resistant to approved therapeutics raises the concern that gonorrhea may become untreatable. Here, we serendipitously identified oxydifficidin as a potent N. gonorrhoeae antibiotic through the observation of a Bacillus amyloliquefaciens contaminant in a lawn of N. gonorrhoeae. Oxydifficidin is active against both wild-type and multidrug-resistant N. gonorrhoeae. It's potent activity results from a combination of DedA-assisted uptake into the cytoplasm and the presence of an oxydifficidin-sensitive ribosomal protein L7/L12 (RplL). Our data indicates that oxydifficidin binds to the ribosome at a site that is distinct from other antibiotics and that L7/L12 is uniquely associated with its mode of action. This study opens a potential new avenue for addressing antibiotic resistant gonorrhea and underscores the possibility of identifying overlooked natural products from cultured bacteria, particularly those with activity against previously understudied pathogens.

Optimal Prone Position Duration in Patients With ARDS Due to COVID-19: The Omelette Pilot Trial.

BACKGROUND: Prone position (PP) has been widely used in the COVID-19 pandemic for ARDS management. However, the optimal length of a PP session is still controversial. This study aimed to evaluate the effects of prolonged versus standard PP duration in subjects with ARDS due to COVID-19. METHODS: This was a single-center, randomized controlled, parallel, and open pilot trial including adult subjects diagnosed with severe ARDS due to COVID-19 receiving invasive mechanical ventilation that met criteria for PP between March-September 2021. Subjects were randomized to the intervention group of prolonged PP (48 h) versus the standard of care PP (∼16 h). The primary outcome variable for the trial was ventilator-free days (VFDs) to day 28. RESULTS: We enrolled 60 subjects. VFDs were not significantly different in the standard PP group (18 [interquartile range [IQR] 0-23] VFDs vs 7.5 [IQR 0-19.0] VFDs; difference, -10.5 (95% CI -3.5 to 19.0, P = .08). Prolonged PP was associated with longer time to successful extubation in survivors (13.00 [IQR 8.75-26.00] d vs 8.00 [IQR 5.00-10.25] d; difference, 5 [95% CI 0-15], P = .001). Prolonged PP was also significantly associated with longer ICU stay (18.5 [IQR 11.8-25.3] d vs 11.50 [IQR 7.75-25.00] d, P = .050) and extended administration of neuromuscular blockers (12.50 [IQR 5.75-20.00] d vs 5.0 [IQR 2.0-14.5] d, P = .005). Prolonged PP was associated with significant muscular impairment according to lower Medical Research Council values (59.6 [IQR 59.1-60.0] vs 56.5 [IQR 54.1-58.9], P = .02). CONCLUSIONS: Among subjects with severe ARDS due to COVID-19, there was no difference in 28-d VFDs between prolonged and standard PP strategy. However, prolonged PP was associated with a longer ICU stay, increased use of neuromuscular blockers, and greater muscular impairment. This suggests that prolonged PP is not superior to the current recommended standard of care.

Using Bibliometric Analysis to Map the Impact of a Simulation Program's Published Scholarly Works.

SUMMARY STATEMENT: Bibliometrics quantitatively evaluates the targeted literature sources and can help define research and scholarly publications' impact and demonstrate connections for authors, departments, or universities. This article presents a methodology for simulation programs to evaluate their influence in terms of both impact and scope of their published simulation-based healthcare scholarly output. Using the authors' home university and healthcare system as an example, the article outlines a methodology to map research and scholarly works networks within the systems, identify and map connections outside the system, and quantifiably score the overall impact of the simulation program's scholarly output using a common scoring metric, the h-index. This generates an objective measure of impact, rather than a subjective opinion of an organization's research and scholarly impact. The combination of an institutional h-index with mapping of simulation-based healthcare scholarly output provides a full, objective description of the institution's output and provides a benchmark for other simulation programs for comparison.

¿Podrían ayudarnos los algoritmos de machine learning en la predicción de hemorragia masiva a nivel prehospitalario? / Could machine learning algorithms help us in predicting massive hemorrhage at the prehospital level?

Objetivo: Comparación de la capacidad predictiva de diferentes algoritmos de machine learning (AML) respecto a escalas tradicionales de predicción de hemorragia masiva en pacientes con enfermedad traumática grave (ETG). Diseño: Sobre una base de datos de una cohorte retrospectiva con variables clínicas prehospitalarias y de resultado de hemorragia masiva se realizó un tratamiento de la base de datos para poder aplicar los AML, obteniéndose un conjunto total de 473 pacientes (80% entrenamiento, 20% validación). Para la modelización se realizó imputación proporcional y validación cruzada. El poder predictivo se evaluó con la métrica ROC y la importancia de las variables mediante los valores Shapley. Ámbito: Atención extrahospitalaria del paciente con ETG. Pacientes: Pacientes con ETG atendidos en el medio extrahospitalario por un servicio médico extrahospitalario desde enero de 2010 hasta diciembre de 2015 y trasladados a un centro de trauma en Madrid. Intervenciones: Ninguna. Variables de interés principales: Obtención y comparación de la métrica ROC de 4 AML: random forest, support vector machine, gradient boosting machine y neural network con los resultados obtenidos con escalas tradicionales de predicción. Resultados: Los diferentes AML alcanzaron valores ROC superiores al 0,85, teniendo medianas cercanas a 0,98. No encontramos diferencias significativas entre los AML. Cada AML ofrece un conjunto de variables diferentes, pero con predominancia de las variables hemodinámicas, de reanimación y de deterioro neurológico. Conclusiones: Los AML podrían superar a las escalas tradicionales de predicción en la predicción de hemorragia masiva. (AU)

Objective: Comparison of the predictive ability of various machine learning algorithms (MLA) versus traditional prediction scales for massive hemorrhage in patients with severe traumatic injury (ETG). Design: On a database of a retrospective cohort with prehospital clinical variables and massive hemorrhage outcome, a treatment of the database was performed to be able to apply the different MLA, obtaining a total set of 473 patients (80% training and 20% validation). For modeling, proportional imputation and cross validation were performed. The predictive power was evaluated with the ROC metric and the importance of the variables using the Shapley values. Setting: Out-of-hospital care of patients with ETG. Participants: Patients with ETG treated out-of-hospital by a prehospital medical service from January 2010 to December 2015 and transferred to a trauma center in Madrid. Interventions: None. Main variables of interest: Obtaining and comparing the ROC curve metric of 4 MLAs: random forest, support vector machine, gradient boosting machine and neural network with the results obtained with traditional prediction scales. Results: The different MLA reached ROC values higher than 0.85, having medians close to 0.98. We found no significant differences between MLAs. Each MLA offers a different set of more important variables with a predominance of hemodynamic, resuscitation variables and neurological impairment. Conclusions: MLA may be helpful in patients with massive hemorrhage by outperforming traditional prediction scales. (AU)

Could machine learning algorithms help us predict massive bleeding at prehospital level?

OBJECTIVE: Comparison of the predictive ability of various machine learning algorithms (MLA) versus traditional prediction scales (TPS) for massive hemorrhage (MH) in patients with severe traumatic injury (STI). DESIGN: On a database of a retrospective cohort with prehospital clinical variables and MH outcome, a treatment of the database was performed to be able to apply the different AML, obtaining a total set of 473 patients (80% training, 20% validation). For modeling, proportional imputation and cross validation were performed. The predictive power was evaluated with the ROC metric and the importance of the variables using the Shapley values. SETTING: Out-of-hospital care of patients with STI. PARTICIPANTS: Patients with STI treated out-of-hospital by a out-of-hospital medical service from January 2010 to December 2015 and transferred to a trauma center in Madrid. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Obtaining and comparing the "Receiver Operating Characteristic curve" (ROC curve) metric of four MLAs: "random forest" (RF), "vector support machine" (SVM), "gradient boosting machine" (GBM) and "neural network" (NN) with the results obtained with TPS. RESULTS: The different AML reached ROC values higher than 0.85, having medians close to 0.98. We found no significant differences between AMLs. Each AML offers a different set of more important variables with a predominance of hemodynamic, resuscitation variables and neurological impairment. CONCLUSIONS: MLA may be helpful in patients with HM by outperforming TPS.

Evaluación de la Calidad de los Agentes Conversacionales para la Creación de Instrumentos de Evaluación en Medición de Señales Bioeléctricas / Evaluation of the Quality of Conversational Agents for the Creation of Evaluation Instruments in Bioelectric Signals Measurement

Resumen El objetivo de esta investigación es evaluar la calidad de agentes conversacionales basados en Modelos de Lenguaje Grandes, para la evaluación de aplicación de conocimiento en Ingeniería Biomédica. Se desarrolló un instrumento de evaluación sobre seis temas de medición de señales bioeléctricas elaborado por un agente humano y los agentes conversacionales Chat-GPT y Bard. Se evaluó la calidad del instrumento en términos de nivel de pensamiento, validez, relevancia, claridad, dificultad y capacidad de discriminación, mediante índice kappa (k) del acuerdo de dos expertos y análisis Rasch de resultados de treinta y ocho estudiantes. Tras eliminar siete preguntas de los agentes conversacionales por problemas de validez y originalidad se integró un instrumento de seis preguntas. Las preguntas fueron válidas y relevantes, claras (>0.95, k=1.0), con dificultad baja a alta (0.61-0.87, k=0.83), índice de discriminación adecuado (0.11-0.47), a nivel de pensamiento de análisis (k=0.22). El promedio de los estudiantes fue de 7.24±2.40. Este es el primer análisis crítico de la calidad de los agentes conversacionales a un nivel de pensamiento superior al de comprensión. Los agentes conversacionales presentaron limitaciones en términos de validez, originalidad, dificultad y discriminación en comparación con el experto humano lo que resalta la necesidad aún de su supervisión.

Abstract This research aims to evaluate the quality of conversational agents based on Large Language Models for evaluating the application of knowledge in Biomedical Engineering. An evaluation instrument was developed on six topics for measuring bioelectrical signals prepared by a human agent and the conversational agents Chat-GPT and Bard. The quality of the instrument was evaluated in terms of level of thinking, validity, relevance, clarity, difficulty, and discrimination capacity, using the kappa (k) index of the agreement of two experts and Rasch analysis of results from thirty-eight students. After eliminating seven questions from the conversational agents due to validity and originality problems, a 6-question instrument was integrated. The questions were valid and relevant, clear (>0.95, k=1.0), with low to high difficulty (0.61-0.87, k=0.83), adequate discrimination index (0.11-0.47), at the analysis level of thinking (k =0.22). The average score of the students was 7.24±2.40. This is the first critical analysis of the quality of conversational agents at a level of thinking higher than comprehension. The conversational agents presented limitations in terms of validity, originality, difficulty, and discrimination compared to the human expert, which highlights the need for their supervision.

Comparison of PHITS2.88 and MCNP6.1 for the characterization of a LUPIN-II neutron area monitor.

The use of different nuclear data libraries and physics models can be a source of discrepancies in neutron transport simulation. Different Monte Carlo simulation toolkits can be used to characterize neutron monitors, these codes usually employ by default different nuclear data libraries and physics models. This work presents, for the first time, a comparison of MCNP and PHITS for the characterization of a LUPIN-II neutron rem-meter. The most significant discrepancies between the codes have been found around 100 MeV.

Improving Glaucoma Diagnosis Assembling Deep Networks and Voting Schemes.

Glaucoma is a group of eye conditions that damage the optic nerve, the health of which is vital for good eyesight. This damage is often caused by higher-than-normal pressure in the eye. In the past few years, the applications of artificial intelligence and data science have increased rapidly in medicine especially in imaging applications. In particular, deep learning tools have been successfully applied obtaining, in some cases, results superior to those obtained by humans. In this article, we present a soft novel ensemble model based on the K-NN algorithm, that combines the probability of class membership obtained by several deep learning models. In this research, three models of different nature (CNN, CapsNets and Convolutional Autoencoders) have been selected searching for diversity. The latent space of these models are combined using the local information provided by the true sample labels and the K-NN algorithm is applied to determine the final decision. The results obtained on two different datasets of retinal images show that the proposed ensemble model improves the diagnosis capabilities for both the individual models and the state-of-the-art results.

Transplantation of hematopoietic progenitors in myelofibrosis.

The objective of this work is to generate recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles published between 1999 and 2015 (January) was used as a source of scientific evidence. The recommendations were produced through a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and the European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention, and management of post-transplant relapse. Patients with intermediate-2 or high-risk disease and age < 70 years should be considered candidates for allo-SCT. Patients with intermediate-risk 1 disease and age < 65 years should be considered candidates if they have refractory transfusion-dependent anemia, or a peripheral blood (PB) blast percentage > 2%, or adverse cytogenetics. Splenectomy before transplantation must be decided on a case-by-case basis. Patients with intermediate-2 or high-risk disease who lack a human leukocyte antigen (HLA)-matched sibling or unrelated donor should be enrolled in a protocol that uses HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for transplants from HLA-matched unrelated donors and siblings. The optimal intensity of the conditioning regimen has yet to be defined. Strategies such as discontinuation of immunosuppressive drugs, infusion of donor lymphocytes, or both were considered adequate to prevent clinical relapse. In conclusion, we provide consensus-based recommendations aimed at optimizing allo-SCT in PMF. Unmet clinical needs were highlighted.

El objetivo de este trabajo es generar recomendaciones sobre el manejo del trasplante alogénico de células madre (alo-SCT) en la mielofibrosis primaria (MFP). Se utilizó una revisión sistemática integral de artículos publicados entre 1999 y 2015 (enero) como fuente de evidencia científica. Las recomendaciones se produjeron mediante un proceso Delphi en el que participó un panel de 23 expertos designados por la European LeukemiaNet y el European Blood and Marrow Transplantation Group. Las preguntas clave incluyeron la selección de pacientes, la selección de donantes, el manejo previo al trasplante, el régimen de acondicionamiento, el manejo posterior al trasplante, la prevención y el manejo de la recaída después del trasplante. Los pacientes con enfermedad de riesgo intermedio 2 o alto y edad < 70 años deben ser considerados candidatos para alo-SCT. Los pacientes con enfermedad de riesgo intermedio 1 y edad < 65 años deben ser considerados candidatos si presentan anemia refractaria dependiente de transfusiones, o un porcentaje de blastos en sangre periférica > 2%, o citogenética adversa. La esplenectomía previa al trasplante debe decidirse caso por caso. Los pacientes con enfermedad de riesgo intermedio 2 o alto que carecen de un hermano compatible con el antígeno leucocitario humano (HLA) o de un donante no emparentado deben inscribirse en un protocolo que utilice donantes no idénticos de HLA. PB se consideró la fuente más apropiada de células madre hematopoyéticas para trasplantes de hermanos y donantes no emparentados compatibles con HLA. La intensidad óptima del régimen de acondicionamiento aún debe definirse. Se consideraron adecuadas estrategias como la suspensión de los fármacos inmunosupresores, la infusión de linfocitos del donante o ambas para evitar la recaída clínica. En conclusión, proporcionamos recomendaciones basadas en consenso destinadas a optimizar el alo-SCT en MFP. Se destacaron las necesidades clínicas insatisfechas.

Essential thrombocythaemia.

Essential thrombocythemia (ET) is a chronic Philadelphia-negative myeloproliferative neoplasm that has its main involvement in the megakaryopoietic lineage, generating sustained thrombocytosis in peripheral blood and an increase in the number of mature megakaryocytes in the bone marrow. In addition to marked thrombocytosis, it is characterized by increased thrombotic or hemorrhagic risk and the presence of constitutional symptoms. Patients with ET have a low but known risk of disease progression to myelofibrosis and/or acute leukemia. The diagnosis is made based on the 2016 WHO criteria. At present, available treatments for patients with ET are mainly aimed at minimizing the risk of thrombosis and/or bleeding.

La trombocitemia esencial (TE) es una neoplasia mieloproliferativa crónica Filadelfia negativa que tiene su principal involucro en la línea megacariopoyética, generando trombocitosis sostenida en la sangre periférica y un incremento en el número de megacariocitos maduros en médula ósea. Además de una marcada trombocitosis, se caracteriza por un mayor riesgo trombótico o hemorrágico y la presencia de síntomas constitucionales. Los pacientes con TE tienen un riesgo bajo, pero conocido, de evolución de la enfermedad a mielofibrosis y/o leucemia aguda. El diagnóstico se realiza con base en los criterios de la Organización Mundial de la Salud del 2016. Los tratamientos actualmente disponibles para los pacientes con TE están dirigidos principalmente a minimizar el riesgo de trombosis y/o hemorragia.

Pregnancy in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are associated with a significant risk of thrombosis and the hypercoagulable environment of pregnancy increases this risk. The most frequent gestational complications consist of spontaneous abortion, thrombosis, bleeding, and hypertensive disease of pregnancy. Treatment depends on thrombotic risk, gestational trimester, and myeloproliferative neoplasm.

Las neoplasias mieloproliferativas (NMP) están asociadas a un riesgo notable de trombosis y el entorno de hipercoagulabilidad propio del embarazo aumenta este riesgo. Las complicaciones gestacionales más frecuentes consisten en: aborto espontáneo, trombosis, sangrado y enfermedad hipertensiva del embarazo. El tratamiento depende del riesgo trombótico, trimestre gestacional y neoplasia mieloproliferativa.

Polycythemia vera.

Polycythemia vera (PV) is mainly characterized by erythrocytosis, thrombotic and hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. The diagnosis is made based on the 2016 WHO criteria. The treatment of PV focuses on rapidly reducing the erythrocyte mass, either by means of phlebotomies or with cytoreductive treatment, and the reduction of thrombotic risk by correcting cardiovascular risk factors and the use of platelet antiaggregants.

La policitemia vera (PV) se caracteriza principalmente por eritrocitosis, predisposición trombótica y hemorrágica, una variedad de síntomas y riesgos acumulativos de progresión fibrótica y/o evolución leucémica a lo largo del tiempo. El diagnóstico se realiza con base en los criterios de la Organización Mundial de la Salud del 2016. El tratamiento de la PV se centra en reducir rápidamente la masa eritrocitaria, ya sea por medio de flebotomías o con tratamiento citorreductor, y la disminución del riesgo trombótico mediante la corrección de factores de riesgo cardiovascular y el uso de antiagregantes plaquetarios.

Risks in invasive procedures.

Patients with myeloproliferative neoplasms have an increased risk of thrombosis and bleeding. This risk must be identified, as well as individualizing the therapeutic strategy before invasive procedures; adequate cytoreduction reduces the risk of complications.

Los pacientes con neoplasias mieloproliferativas tienen un riesgo incrementado de trombosis y sangrado. Se debe identificar dicho riesgo, así como individualizar la estrategia terapéutica previo a los procedimientos invasivos; una adecuada citorreducción disminuye el riesgo de complicaciones.

Symptom control.

In addition to symptoms secondary to splenomegaly, microvascular abnormalities, and thrombohemorrhagic complications, patients with MPN may experience a significant symptom burden attributed to an increase in circulating inflammatory cytokines. These symptoms can be severe and limit quality of life. Therefore, in addition to the prevention of complications, one of the objectives of the treatment of MPN is the control of symptoms.

Además de la sintomatología secundaria a la esplenomegalia, a las alteraciones microvasculares y a las complicaciones trombohemorrágicas, los pacientes con neoplasias mieloproliferativas (NMP) pueden experimentar una importante carga sintomática atribuida a un aumento de citocinas inflamatorias circulantes. Estos síntomas pueden ser severos y limitar la calidad de vida. Por ello, además de la prevención de las complicaciones, uno de los objetivos del tratamiento de las NMP es el control de los síntomas.

Thrombotic events.

Major thrombotic complications in myeloproliferative neoplasms (MPNs) represent an important clinical problem due to their high morbidity, the complexity of their management, and their associated mortality. The appearance of a thrombosis implies a high thrombotic risk stratification of the MPN and determines the initiation or optimization of cytoreductive treatment and the use of antiplatelet or anticoagulant therapy as secondary prophylaxis. The incidence of thrombosis at the time of diagnosis is higher than during the course of the disease, being located in the arterial territory in 60-70% of cases. Once thrombosis has occurred, up to 20-33% of patients experience thrombotic recurrence in the same initial vascular territory.

Las complicaciones trombóticas mayores en las neoplasias mieloproliferativas (NMP) representan un importante problema clínico debido a su elevada morbilidad, la complejidad de su manejo y su mortalidad asociada. La aparición de una trombosis comporta una estratificación de alto riesgo trombótico de la NMP y determina el inicio o la optimización del tratamiento citorreductor y el uso de terapia antiplaquetaria o anticoagulante como profilaxis secundaria. La incidencia de trombosis en el momento del diagnóstico es mayor que durante la evolución de la enfermedad, localizándose en territorio arterial en el 60-70% casos. Una vez se ha producido una trombosis, hasta el 20-33% de los pacientes sufre una recurrencia trombótica en el mismo territorio vascular inicial.

First inter-institutional consensus on Chronic Myeloproliferative Neoplasms.

The objective of the consensus is to make available to the professionals of the different public health institutions in our country, who are in charge of these diseases, the most relevant and up-to-date information about their diagnosis and treatment in clinical practice. With this inter-institutional consensus we hope to contribute to improving the quality of care for patients with chronic myeloproliferative neoplasms throughout the Mexican Republic, to unify criteria in both diagnosis and treatment of the different myeloproliferative diseases.

OBJETIVO: El objetivo del consenso es poner a disposición de los profesionales de las diferentes instituciones de salud pública en nuestro país, quienes se encuentran a cargo de estas enfermedades, la información más relevante y actualizada acerca de su diagnóstico y tratamiento en la práctica clínica. Con este consenso interinstitucional esperamos contribuir a mejorar la calidad de la atención de los pacientes con neoplasias mieloproliferativas crónicas a todo lo ancho y largo de la República Mexicana, con el fin de unificar criterios tanto en diagnóstico como en tratamiento de las diferentes enfermedades mieloproliferativas.

Myelofibrosis: diagnosis and treatment.

Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm characterized by clonal myeloproliferation, dysregulated kinase signaling, and release of abnormal cytokines. In recent years, important progress has been made in the knowledge of the molecular biology and the prognostic assessment of MF. Conventional treatment has limited impact on the patients' survival; it includes a wait-and-see approach for asymptomatic patients, erythropoiesis-stimulating agents, androgens, or immunomodulatory agents for anemia, cytoreductive drugs such as hydroxyurea for the splenomegaly and constitutional symptoms, and splenectomy or radiotherapy in selected patients. The discovery of the Janus kinase (JAK) 2 mutation triggered the development of molecular targeted therapy of MF. The JAK inhibitors are effective in both JAK2-positive and JAK2-negative MF; one of them, ruxolitinib, is the current best available therapy for MF splenomegaly and constitutional symptoms. Although ruxolitinib has changed the therapeutic scenario of MF, there is no clear indication of a disease-modifying effect. Allogeneic stem cell transplantation remains the only curative therapy of MF, but due to its associated morbidity and mortality, it is usually restricted to eligible high- and intermediate-2-risk MF patients. To improve current therapeutic results, the combination of JAK inhibitors with other agents is currently being tested, and newer drugs are being investigated.

La mielofibrosis (MF) es una neoplasia mieloproliferativa negativa para BCR-ABL1 caracterizada por mieloproliferación clonal, señalización de cinasa desregulada y liberación de citocinas anormales. En los últimos años se han realizado importantes avances en el conocimiento de la biología molecular y la valoración pronóstica de la MF. El tratamiento convencional tiene un impacto limitado en la supervivencia de los pacientes; incluye un enfoque de espera para pacientes asintomáticos, agentes estimulantes de la eritropoyesis, andrógenos o agentes inmunomoduladores para la anemia, fármacos citorreductores como la hidroxiurea para la esplenomegalia y los síntomas constitucionales, y esplenectomía o radioterapia en pacientes seleccionados. El descubrimiento de la mutación Janus cinasa (JAK) 2 desencadenó el desarrollo de la terapia dirigida molecular de la MF. Los inhibidores de JAK son efectivos tanto en MF con JAK2 positivo como con JAK2 negativo; uno de ellos, el ruxolitinib, es la mejor terapia disponible actualmente para la esplenomegalia y los síntomas constitucionales de la MF. Sin embargo, aunque el ruxolitinib ha cambiado el escenario terapéutico de la MF, no hay indicios claros de un efecto modificador de la enfermedad. El alotrasplante de células madre sigue siendo la única terapia curativa de la MF, pero debido a su morbilidad y mortalidad asociadas, generalmente se restringe a pacientes elegibles con MF de riesgo alto e intermedio 2. Para mejorar los resultados terapéuticos actuales, actualmente se está probando la combinación de inhibidores de JAK con otros agentes y se están investigando fármacos más nuevos.

Elevated monocyte distribution width in trauma: An early cellular biomarker of organ dysfunction.

INTRODUCTION: Traumatic injury elicits an inflammatory response such as the one occurring during systemic infection. Monocyte distribution width (MDW) has been found to distinguish sepsis in a pool of patients with suspected infection. We hypothesized that an elevated MDW in trauma patients would be associated with the development of multiple organ dysfunction syndrome (MODS) and an increased mortality. MATERIALS AND METHODS: Observational study in a dedicated trauma Intensive Care Unit (ICU) in Madrid during 2019-2020. Patients were classified according to their first MDW value on admission, as greater or lesser than 21 U. Clinical data was obtained and univariate and multivariate analysis were realized, as well as a test performance analysis. RESULTS: 354 patients were studied, with a median age of 46 years, 78% male. Half presented with severe trauma ISS > 15, mostly with a blunt mechanism of injury. A MDW ≥ 21 U on admission was found in 17% of cases. These patients were more likely to present with hemodynamic instability and MODS. They had a higher length of stay (3.8 vs 2 days) and higher mortality (21 vs 5%) compared to the low MDW group. These findings remained statistically significant in the multivariate analysis, with an OR 4.6 (IC 95% 1.7-12) for MODS and 3.1 (IC 95% 1.2-8.3) for mortality. CONCLUSIONS: In trauma patients, a MDW ≥ 21 U on admission was independently associated with a greater risk of MODS, a higher mortality and a higher length of stay. This biomarker could be useful in predicting severity in the initial evaluation of trauma patients.