Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol.

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear. Our results suggest that elevated 27-OH decreases the astrocyte function in vivo in Cyp27Tg, a mouse model of brain oxysterol imbalance. Here, we report a downregulation of glutamate transporters in the hippocampus of CYP27Tg mice together with increased GFAP. GLT-1 downregulation was also observed when WT mice were fed with high-cholesterol diets. To study the relationship between astrocytes and neurons, we have developed a 3D co-culture system that allows all the cell types from mice embryos to differentiate in vitro. We report that our 3D co-cultures reproduce the effects of 27-OH observed in 2D neurons and in vivo. Moreover, we found novel degenerative effects in astrocytes that do not appear in 2D cultures, together with the downregulation of glutamate transporters GLT-1 and GLAST. We propose that this transporter dysregulation leads to neuronal hyperexcitability and synaptic dysfunction based on the effects of 27-OH on astrocytes. Taken together, these results report a new mechanism linking oxysterol imbalance in the brain and synaptic dysfunction through effects on astrocyte function.

Frailty, Seasonal Sensitivity and Health-related Quality of Life in Older People Living in High Southern Latitudes: a Bayesian Analysis.

Background: In older people, a notable research gap exists regarding the intricate dynamics between frailty, seasonal sensitivity, and health-related quality of life (HRQoL). This study aimed to determine the association between frailty, seasonal sensitivity, and HRQoL in older people from high southern latitudes. Methods: A cross-sectional observational study was conducted. Frailty, seasonal sensitivity, and HRQoL measurements were self-reported by participants through questionnaires. A total of 118 older people were recruited from a local community. The participants were selected through intentional non-probabilistic sampling. Results: The adjusted models showed a trend where lower education was associated with a higher risk of frailty (BF = 0.218). For frailty and HRQoL, we observed a trend suggesting that HRQoL decreases with increasing severity of frailty (BF = 1.76). In addition, we observed a linear effect based on the severity of seasonal sensitivity, meaning that older people with higher perceived severity report a proportional decrease in HRQoL (BF = 6.66). Conclusion: Sociodemographic factors, such as lower education levels, have increased the risk of frailty. At the same time, frailty and seasonal sensitivity perceived severity were associated with a lower HRQoL in older people.

Children with cancer at the end of life in a middle-income country: integrated pediatric palliative care improves outcomes.

BACKGROUND: In 2020, the Global Cancer Observatory reported 280,000 cases of childhood cancer worldwide, with a higher burden of disease and mortality rates in low- and middle-income countries. In 2022, the National Institute of Health reported 1708 new cases of childhood cancer in Colombia and an overall survival rate of approximately 55%. The aim of this study is to compare outcomes in children with cancer in the hospital setting during the last 72 h of life who received concurrent Pediatric Palliative Care (PPC) versus oncology care alone. METHODS: An observational descriptive study was conducted between January 2013 and June 2022 in a center for pediatric patients with oncological diagnoses. In 2017, the PPC team was created. Patients between 28 days and 17 years of age who were hospitalized at least 72 h before death were included. A retrospective review of the medical records of patients in the last 72 h of life was performed. Two cohorts were established: oncology-alone group received exclusive management by oncology, and oncology and PPC received concurrent oncology and PPC management since the diagnosis. RESULTS: We evaluated 257 medical records of deceased pediatric patients with cancer diagnoses. For the first cohort (2013-2017), 136 patients were included; for the second cohort (2018 and 2022), 121 patients were evaluated. The most frequent diagnosis was leukemia [47.1% (n = 121)]. No significant difference was found in either group between dyspnea, pain, and seizures. Dyspnea was the most frequent symptom in both groups. Agitation and anxiety were reported more frequently in children from the oncology-alone group (22.1% and 13.2%, respectively). The oncology and PPC group received more psychology and social work consultation (94.2% and 70.2% vs. 84.6 and 54.4% in the oncology alone group) and had a higher percentage of advance care planning (79.3% vs. 62.5% in the oncology alone group). CONCLUSIONS: This retrospective study highlights that PPC at the end of life (EoL) offers a holistic approach to the physical and psychosocial symptoms experienced by children with cancer; these patients received more comfort through symptom management and less aggressive treatment at the EoL. The availability of a PPC team may contribute to improvements in the quality of end-of-life care. TRIAL REGISTRATION: retrospectively registered.

A parsimonious approach to predict regions affected by sewer-borne contaminants in urban aquifers.

Leaky urban drainage networks (UDNs) exfiltrating wastewater can contaminate aquifers. Detailed knowledge on spatiotemporal distributions of water-dissolved, sewer-borne contaminants in groundwater is essential to protect urban aquifers and to optimize monitoring systems. We evaluated the effect of UDN layouts on the spreading of sewer-borne contaminants in groundwater using a parsimonious approach. Due to the UDN's long-term leakage behavior and the existence of non-degradable sewer-borne contaminants (equivalent to a conservative and constant contaminant source), we employed a concept of horizontal line sources to mimic the UDN layout. This does not require the consideration of bio-degradation processes or temporal delay and effectively bypasses the vadose zone, thus reducing computational requirements associated with a full simulation of leakages. We used a set of synthetic leakage scenarios which were generated using fractals and are based on a real-world UDN layout. We investigated the effects of typical leakage rates, varying groundwater flow directions, and UDN's layouts on the shape of the contaminant plume, disregarding the resulted concentration. Leakage rates showed minimal effects on the total covered plume area, whereas 89% of the variance of the plume's geometry is explained by both the UDN's layout (e.g., length and level of complexity) and groundwater flow direction. We demonstrated the potential of applying this approach to identify possible locations of groundwater observation wells using a real UDN layout. This straightforward and parsimonious method can serve as an initial step to strategically identify optimal monitoring systems locations within urban aquifers, and to improve sewer asset management at city scale.

Diagnostic accuracy of the BioFire® FilmArray® pneumonia panel in COVID-19 patients with ventilator-associated pneumonia.

BACKGROUND: Ventilator-Associated pneumonia (VAP) is one of the leading causes of morbidity and mortality in critically ill COVID-19 patients in lower-and-middle-income settings, where timely access to emergency care and accurate diagnostic testing is not widely available. Therefore, rapid microbiological diagnosis is essential to improve effective therapy delivery to affected individuals, preventing adverse outcomes and reducing antimicrobial resistance. METHODS: We conducted a cross-sectional study of patients with suspected VAP and COVID-19, evaluating the diagnostic performance of the BioFire® FilmArray® Pneumonia Panel (FA-PP). Respiratory secretion samples underwent standard microbiological culture and FA-PP assays, and the results were compared. RESULTS: We included 252 samples. The traditional culture method detected 141 microorganisms, and FA-PP detected 277, resulting in a sensitivity of 95% and specificity of 60%, with a positive predictive value of 68% and negative predictive value of 93%. In samples with high levels of genetic material (> 10^5 copies/mL), the panel had a sensitivity of 94% and specificity of 86%. In addition, 40% of the culture-negative samples had positive FA-PP® results, of which 35% had > 10^5 copies/mL of genetic material. The most prevalent bacteria were Gram-negative bacilli, followed by Gram-positive cocci. The panel identified 98 genes associated with antimicrobial resistance, predominantly extended-spectrum beta-lactamases (28%). CONCLUSION: The FA-PP is a sensitive assay for identifying bacteria causing VAP in patients with COVID-19, with a greater capacity to detect bacteria than the conventional method. The timely microbiological recognition offered by this panel could lead to optimized decision-making processes, earlier tailored treatment initiation, and improved antibiotic stewardship practices.

Genomic landscape of virus-associated cancers.

It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we present a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We find that virus-positive tumors occur more frequently in males and show geographical disparities in incidence. Genomic analysis of 1,658 tumors reveals virus-positive tumors exhibit distinct mutation signatures and driver gene mutations and possess a lower somatic mutation burden compared to virus-negative tumors of the same cancer type. For example, compared to the respective virus-negative counterparts, virus-positive cases across different cancer histologies had less often mutations of TP53 and deletions of 9p21.3/ CDKN2 A- CDKN1A ; Epstein-Barr virus-positive (EBV+) gastric cancer had more frequent mutations of EIF4A1 and ARID1A and less marked mismatch repair deficiency signatures; and EBV-positive cHL had fewer somatic genetic lesions of JAK-STAT, NF-κB, PI3K-AKT and HLA-I genes and a less pronounced activity of the aberrant somatic hypermutation signature. In cHL, we also identify germline homozygosity in HLA class I as a potential risk factor for the development of EBV-positive Hodgkin lymphoma. Finally, an analysis of clinical trials of PD-(L)1 inhibitors in four virus-associated cancers suggested an association of viral infection with higher response rate in patients receiving such treatments, which was particularly evident in gastric cancer and head and neck squamous cell carcinoma. These results illustrate the epidemiological, genetic, prognostic, and therapeutic trends across virus-associated malignancies.

Determination of the Anthropometric Measures of the Lips by Age Groups in the Mestiza Population.

Measurements from a certain population may show a similar pattern that allows an alteration to be easily recognized and enable a better surgical approach. In our population, the changes in the anthropometric measurements of the lips are unknown, so our objective is to determine the variations in these measurements by decades of age to achieve a better aesthetic and reconstructive surgical approach. Anthropometric measurements of the lips were taken with a vernier in relation to the previously marked anatomical points. The sample consists of 174 patients who came for care not related to labial pathologies with ages between 20 and 80 years with Mexican nationality. We use the sample calculation formula to estimate an average, with an alpha error of 0.5 and a tolerance of 2 mm of the data for the measurements of the height of the lower face with an average measurement of 56.2 mm and a SD of 8.87 mm of the Marzena's article. Wyganowska-Swiatkowska and colleagues Average measurements were obtained, where a progressive longitudinal increase in measures: al-ch, sbl-cph, sn-Is, li-sto, cph-Is, li-sl, ch-li, li-pg according to aging is confirmed. In contrast, the ch-cph and ch-sbl measures, remain the same despite the aging, showing greater changes in the sagittal plane than in the parasagittal. The study only shows measures of length, so caring out a magnetic resonance imaging study to also measure the volume and perform it with a larger sample to have the optimal standard is further needed.

[Cutaneous hyperpigmentation as a manifestation in acute on chronic liver failure]. / Hiperpigmentación cutánea como manifestación poco reconocida en falla hepática aguda sobre crónica.

Background: The acquired cutaneous pigmentation represents a little recognized clinical manifestation in liver disorders, both acute and chronic, and can occur in the exacerbation processes of preexisting hepatopathies, as in the context of acute-on-chronic liver failure. Several hypotheses about the increase in pigment at skin and mucous membranes have been developed; some try to explain it as a defect in the degradation of melanin with secondary accumulation at tissues; others, on the other hand, describe it as a consequence of the release of fibroblast growth factors like endothelial growth factor and hepatocyte growth factor, which are produced under the stimulation of liver regeneration and cause a melanogenesis stimulation. The aim of this article is to study pigmentary skin changes in the background of liver diseases. Clinical cases: We described two clinical cases of patients with acuteon chronic liver failure secondary to different clinical scenarios are presented, who have in common the development of acquired pigmentary skin changes. Conclusion: In hepatopathies, the cutaneous hyperpigmentation is a sign with unknown etiology, so further studies are required to know the accurate pathophysiology. Reporting this finding is useful for physicians, since timely identification can help in the early diagnosis of underlying liver diseases.

Introducción: la hiperpigmentación cutánea adquirida representa una manifestación clínica poco reconocida en los trastornos hepáticos, tanto agudos como crónicos, y puede presentarse tanto en procesos de agudización de hepatopatías preexistentes como en el contexto de la falla hepática aguda sobre crónica. Se han desarrollado diversas hipótesis sobre el aumento de pigmento a nivel piel y mucosas, algunas tratan de explicarlo por un defecto en la degradación de la melanina, lo cual genera su acumilación en los tejidos; otras, en cambio, describen la liberación de factores de crecimiento derivados de fibroblastos, como el factor de crecimiento endotelial y el factor de crecimiento de hepatocitos, los cuales son producidos bajo el estímulo de la regeneración hepática y, a su vez, provocan una estimulación de la melanogénesis. El objetivo de este trabajo es estudiar la hiperpigmentación cutánea en el contexto de enfermedades hepáticas. Casos clínicos: se presentan dos casos clínicos de pacientes con falla hepática aguda sobre crónica secundaria a diferentes escenarios clínicos, quienes tienen en común el desarrollo pigmentación cutánea adquirida. Conclusiones: en las enfermedades hepáticas, la hiperpigmentación cutánea es un hallazgo presente cuya etiología aún no es dilucidada, por lo que se requieren más estudios para conocer la fisiopatología exacta. El reporte de este hallazgo es de utilidad para el personal médico, ya que la identificación oportuna puede ayudar a el diagnóstico temprano de hepatopatías subyacentes.

Hydrodechlorination of Aryl Chlorides Under Biocompatible Conditions.

Developing nonenzymatic chemistry that is nontoxic to microbial organisms creates the potential to integrate synthetic chemistry with metabolism and offers new remediation strategies. Chlorinated organic compounds known to bioaccumulate and cause harmful environmental impact can be converted into less damaging derivatives through hydrodehalogenation. The hydrodechlorination of substituted aryl chlorides using Pd/C and ammonium formate in biological media under physiological conditions (neutral pH, moderate temperature, and ambient pressure) is reported. The reaction conditions were successful for a range of aryl chlorides with electron-donating and -withdrawing groups, limited by the solubility of substrates in aqueous media. Soluble substrates gave good yields (60-98%) of the reduction product within 48 h. The relative toxicities of each reaction component were tested separately and together against bacteria, and the reaction proceeded in bacterial cultures containing an aryl chloride with robust cell growth. This work offers an initial step toward the removal of aryl chlorides from waste streams that currently use bacterial degradation to remove pollutants.

Achievement rate and predictive factors of the recommended therapeutical target in patients with axial spondyloarthritis who remain on biological therapy: a prospective cohort study in Spain.

OBJECTIVES: To determine the frequency of sustained remission (R) or low diseas activity (LDA) in patients with axial spondyloarthritis (axSpA) undergoing long-term biological therapy and to analyse predictive factors for achieving these outcomes. DESIGN: Prospective, observational cohort study. SETTING: Spanish hospital. PARTICIPANTS: Patients with axSpA who initiated biological treatment between 2003 and 2017. INTERVENTION: Assessment of demographic and clinical characteristics at the beginning of treatment and disease activity every 6 months up to a maximum of 2 years. MAIN OUTCOME MEASURES: Disease activity was measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (BASDAI&CRP). Sustained R was defined as ASDAS<1.3 and/or BASDAI <2 and normal CRP while sustained LDA was defined as ASDAS <2.1 and/or BASDAI <4 and normal CRP on at least three consecutive visits. RESULTS: In total 186 patients (66.1% men and 75.3% with radiographic sacroiliitis) were included. Overall, 76.8% of patients achieved ASDAS R/LDA (R53.2%/LDA23.6%) in at least one visit. Forty per cent (R17.6%/LDA22.4%) of the patients fulfilled the sustained ASDAS R/LDA state, whereas only 30.8% maintained this status (R14.8%/LDA15.9%) according to BASDAI&CRP. In the multivariate analysis, male sex (OR=4.01), younger age at the beginning of biological therapy (OR=0.96) and an HLA*B27 positive status (OR=4.30) were associated with achieving sustained ASDAS R/LDA. CONCLUSIONS: In clinical practice, around one-third of patients on biological disease-modifying antirheumatic drugs achieve a sustained R/LDA status, but these rates drop to less than one in five when targeting remission, preventing the use of the latter as a feasible target. Male sex, HLA*B27 positivity and younger age at the beginning of biological therapy are the main predictors for achieving sustained R/LDA.

Elicitation of isoflavonoids in Colombian edible legume plants with jasmonates and structurally related compounds.

Common bean (Phaseolus vulgaris L.), soybean (Glycine max L.) and mung bean (Vigna radiata L. Wilczek) seedlings were treated with methyl jasmonate (MeJA); then, dose-response and time-course experiments were carried out. Isoflavonoid composition was evaluated by high performance liquid chromatography. As a result of MeJA induction, all leguminous plants increase the amount of isoflavonoids, at levels that depend on the concentration of the elicitor and the time after induction. However, the application of MeJA in concentrations higher than 2.22 mM showed deleterious effects on seedlings and strong decreases in the concentration of isoflavonoids. In addition, a series of compounds structurally related to MeJA, such as jasmonic acid, cis-jasmone, coronatine, and indanoyl derivatives, were evaluated as elicitors. The results show that coronatine and the indanoyl-amino acids conjugates displayed a significant elicitor effect of isoflavonoids in common bean (cvs. Cargamanto Mocho and Corpoica LAS 106) and soybean (cv. Soyica P-34) seedlings, even higher than that found with the recognized elicitors, benzo (1,2,3) thiadiazole-7-carbothioic acid S-methyl ester (acibenzolar S-methyl) and benzo-(1,2,3) thiadiazole-7-carbothioic acid (acibenzolar acid). Leguminous plants can be treated with jasmonates and indanoyl derivatives to increase levels of bioactive isoflavonoids and consequently improve biological and functional properties and resistance against pests.

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.