Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans.

Frecuencia de Ponticulus posticus en Telerradiografías Laterales de Cráneo / Frequency of Ponticulus posticus in Digital Lateral Cephalograms

En el arco posterior del atlas se describe una variación de tejido óseo denominada Ponticulus posticus (PP), la cual se ha relacionado con el desarrollo de dolor cervical. El objetivo de este estudio fue determinar la frecuencia de PP en telerradiografías laterales digitales. Este estudio correspondió a un estudio observacional descriptivo, donde se analizaron 450 telerradiografías laterales digitales obtenidas de la base de datos del Servicio de Imagenología Oral y Maxilofacial de la Facultad de Odontología de la Universidad Andrés Bello, Viña del Mar, Chile. Se analizó la presencia de PP en cada cefalograma, y se utilizó la clasificación de Cederberg y Stubbs para determinar los grados de osificación. Se aplicó la prueba de Chi-cuadrado para establecer una asociación entre la presencia de PP con el sexo y la edad. De las 450 telerradiografías laterales el 42,4 % presenta PP, con una mayor prevalencia entre el rango de 21-40 años. En cuanto al grado de osificación, el grado 2 fue el tipo más prevalente (25 %), seguido del grado 4 (9,5 %), el grado 3 (8 %). No se encontró asociación entre la presencia de PP con edad y género (P > 0,05). La PP es frecuente en la población y se observa a diferentes edades sin predilección por sexo.

SUMMARY: A bony tissue variation called Ponticulus posticus (PP) is described in the posterior arch of the atlas, which has been associated with the development of cervical pain. The aim of this study was to determine the frequency of PP in digital lateral cephalograms. This study was an observational descriptive study, in which 450 digital lateral cephalograms obtained from the database of the Oral and Maxillofacial Imaging Service of the Faculty of Dentistry of the Andrés Bello University, Viña del Mar, Chile, were analyzed. The presence of PP was analyzed in each cephalogram, and the Cederberg and Stubbs classification was used to determine the degrees of ossification. The Chi-square test was applied to establish an association between the presence of PP with gender and age. Of the 450 lateral cephalograms, 42.4 % presented PP, with a higher prevalence in the 21-40 year range. In terms of the degree of ossification, grade 2 was the most prevalent type (25 %), followed by grade 4 (9.5 %), and grade 3 (8 %). No association was found between the presence of PP with age and gender (P > 0.05). PP is common in the population and is observed at different ages without a sex preference.

An ecological study on reinfection rates using a large dataset of RT-qPCR tests for SARS-CoV-2 in Santiago of Chile.

Introduction: As the SARS-CoV-2 continues to evolve, new variants pose a significant threat by potentially overriding the immunity conferred by vaccination and natural infection. This scenario can lead to an upswing in reinfections, amplified baseline epidemic activity, and localized outbreaks. In various global regions, estimates of breakthrough cases associated with the currently circulating viral variants, such as Omicron, have been reported. Nonetheless, specific data on the reinfection rate in Chile still needs to be included. Methods: Our study has focused on estimating COVID-19 reinfections per wave based on a sample of 578,670 RT-qPCR tests conducted at the University of Santiago of Chile (USACH) from April 2020 to July 2022, encompassing 345,997 individuals. Results: The analysis reveals that the highest rate of reinfections transpired during the fourth and fifth COVID-19 waves, primarily driven by the Omicron variant. These findings hold despite 80% of the Chilean population receiving complete vaccination under the primary scheme and 60% receiving at least one booster dose. On average, the interval between initial infection and reinfection was found to be 372 days. Interestingly, reinfection incidence was higher in women aged between 30 and 55. Additionally, the viral load during the second infection episode was lower, likely attributed to Chile's high vaccination rate. Discussion: This study demonstrates that the Omicron variant is behind Chile's highest number of reinfection cases, underscoring its potential for immune evasion. This vital epidemiological information contributes to developing and implementing effective public health policies.

Autologous Stem Cell Transplant in Lymphoma Using a Noncryopreserved Platform: An Adapted Sequential Conditioning Maintaining Dose Intensity Does not Affect Transplantation Outcomes.

BACKGROUND: Hematopoietic autologous stem cell transplantation (ASCT) is a validated therapeutic strategy for lymphoma treatment and precise well-tolerated conditioning. Several conditioning methods are available, but the most commonly used are CVB, BEAM, and ICE, which are conventionally administered in 6 to 7 days. Since 2015, our program has moved toward noncryopreserved platforms that require concise times; therefore, we have modified the conditioning by reducing it to 4 to 5 days. In this study, we show our experience. METHODS: We compared ASCT performed in our program before and after 2015 in lymphoma patients. Between 2000 and 2014 and from 2015 to 2022, we performed 46 and 61 ASCT procedures, respectively. RESULTS: Since 2015, we observed a greater number of infused stem cells, fewer episodes of febrile neutropenia (60% vs. 37% P = .008), shorter hospitalizations (30 vs. 18 days P = .001), faster engraftment (20 vs. 14 days P = .001) and better progression-free survival (72 vs. 44 months P = .002). Additionally, a prolonged overall survival was observed at these results, and this prolonged survival is difficult to interpret due to the short follow-up. CONCLUSION: In conclusion, conditioning adjusted for a noncryopreserved strategy offers at least similar or even better results than the cryopreserved strategy. Prospective studies are warranted.

Concordance of the vestibular bone thickness at the level of point a between teleradiography and cone beam computed tomography / Concordancia del espesor óseo vestibular a nivel del punto a entre telerradiografía y tomografía computarizada de haz cónico

Objective: The aim of this study was to determine the concordance of the vestibular bone thickness measured at the level of point A between Teleradiography and Cone Beam Computed Tomography (CBCT). Materials and Methods: This study consisted of a cross-sectional analytical design of concordance that evaluated the teleradiographies and CBCTs of 32 patients. The measurements were performed by three evaluators, specialists in orthodontics. Two of them measured the CBCTs and one evaluated the teleradiographs. The concordance of both tests was determined using the Concordance Correlation Coefficient. Results: When evaluating the value of the vestibular bone thickness at the level of point A between the CBCT and the teleradiography, it was observed that the mean value of the absolute difference between the two was 0.95±0.74, 95%CI [0.68­1.22], being statistically significant (p=0.0027). When the concordance between both tests was analyzed, it was observed that it was poor (CCC=0.204 95%CI [0.014­0.394]), although statistically significant (p<0.00001). Conclusions: It was possible to conclude that there is no concordance in the measurement of the vestibular bone thickness at the level of Point A between the Teleradiography and the CBCT.

Objetivo: El objetivo de este estudio fue determinar la concordancia del espesor óseo vestibular medido a nivel del punto A entre la Telerradiografía y la Tomografía computarizada de haz cónico (CBCT). Materiales y Métodos: Esta investigación presentó un diseño analítico transversal de concordancia en el que se evaluaron las telerradiografías y CBCT de 32 pacientes. Las mediciones fueron realizadas por tres evaluadores especialistas en ortodoncia, dos de ellos midieron los CBCT y uno las telerradiografías. La concordancia de ambos exámenes fue medida mediante Coeficiente de Correlación de Concordancia. Resultados: Al evaluar el valor del grosor óseo vestibular a nivel del punto A entre el CBCT y la telerradiografía, se observó que el valor promedio de diferencia absoluta entre ambos fue de 0,95±0,74 IC95% [0,68­1,22], siendo estadísticamente significativas (p=0,0027). Cuando se analizó la concordancia entre ambos exámenes se observó que esta fue pobre (CCC=0,204 IC95 % [0,014­0,394]), aunque estadísticamente significativa (p<0,00001). Conclusión: Se pudo concluir que no existe concordancia en la medición del espesor óseo vestibular medido a nivel del Punto A entre la Telerradiografía y el CBCT.

Sensitivity analysis of rapid antigen tests for the Omicron SARS-CoV-2 variant detection from nasopharyngeal swab samples collected in Santiago of Chile.

The COVID-19 pandemic continues to be a concern and keeps global health authorities on alert. The RT-PCR technique has been the gold-standard assay for detecting the SARS-CoV-2 virus. However, rapid antigen tests (RATs) have been widely used to increase the number of tests faster and more efficiently in the population. Nevertheless, the appearance of new viral variants, with genomic mutations associated with greater contagiousness and immune evasion, highlights the need to evaluate the sensitivity of these RATs. This report evaluates the sensitivity of SD Biosensor-Roche, Panbio™, and Clinitest® RATs widely used in Santiago de Chile in the detection of the Omicron variant from Nasopharyngeal samples (NPSs), the most predominant SARS-CoV-2 variant in Chile and the world. SD Biosensor-Roche shows a detection sensitivity of 95.7% in the viral amplification range of 20 ≤ Cq < 25, while Panbio™ and Clinitest® show 100% and 91.3%, respectively. In the viral amplification ranges of 25 ≤ Cq < 30, the detection sensitivity decreased to 28% for SD Biosensor-Roche, 32% for Panbio™, and 72% for Clinitest®. This study indicates that the tested RATs have high sensitivity in detecting the Omicron variant of concern (VOC) at high viral loads. By contrast, its sensitivity decreases at low viral loads. Therefore, it is suggested to limit the use of RATs as an active search method, considering that infections in patients are increasingly associated with lower viral loads of SARS-CoV-2. These antecedents could prevent contagion outbreaks and reduce the underestimation of the current Omicron variant circulation at the local level.

Epidemiological characteristics of Omicron and Delta SARS-CoV-2 variant infection in Santiago, Chile.

The variant of concern (VOC) SARS-CoV-2 Omicron (B.1.1529) has been described as a highly contagious variant but less virulent than the current variant being monitored (VBM) Delta (B.1.617.2), causing fewer cases of hospitalizations, symptomatology, and deaths associated with COVID-19 disease. Although the epidemiological comparison of both variants has been previously reported in other countries, no report indicates their behavior and severity of infection in Chile. In this work, we report for the first time the effect of the Omicron and Delta variants in a cohort of 588 patients from the Hospital de Urgencia Asistencia pública (HUAP), a high-complexity health center in Santiago, Chile. This report is framed at the beginning of Chile's third wave of the COVID-19 pandemic, with a marked increase in the Omicron variant and a decrease in the circulating Delta variant. Our results indicated a similar proportion of patients with a complete vaccination schedule for both variants. However, the Delta variant was associated with a higher prevalence of hospitalization and more significant symptomatology associated with respiratory distress. On the other hand, our data suggest that vaccination is less effective in preventing infection by the Omicron variant. This antecedent, with a low severity but high contagiousness, suggests that the Omicron variant could even collapse the primary health care service due to the high demand for health care.

Prevalence and C-shaped root canal configuration in lower molars in the metropolitan region, Chile / Prevalencia y configuración de conductos en C en molares inferiores de la región metropolitana, Chile

Objetive: The aim of this study was to determine the prevalence, demographics, and root configuration of C-shaped canals of mandibular molars by means of cone beam computed tomography in the population of the Metropolitan Region, Chile. Material and Methods: 912 molars (456 first and 456 second molars) resulting from the analysis of 228 mandibular CT scans were evaluated. The root configuration was established by means of a panoramic reconstruction and axial tomographic sections, classifying the presence and type of canals through the analysis of five sections or cuts along the root. Data were statistically analyzed using a 5% confidence interval. Results: Of the 912 molars analyzed, 70 were classified as C-shaped canals (7.68%), corresponding to 58.33% of those molars that presented fused roots. 95.7% of this root canal configuration was observed in lower second molars, occurring more frequently in females (n=45, 64.29%). 45.65% of the cases that presented C-shaped canals were bilateral and the most frequent configuration was C3 (n=401, 66.63%) according to the Melton classification.Conclusion: The C-shaped canals of the mandibular molars in the studied population were observed mainly in second molars, showing a clear prevalence among females and a high percentage of bilaterality. The presence of fused roots significantly increases the possibility of finding this type of root configuration.

Objetivo: El objetivo del presente estudio fue determinar, por medio de tomografía computarizada de haz cónico, la prevalencia, demografía y configuración radicular de los conductos en forma de C de molares inferiores en la población de la Región Metropolitana, Chile. Material y Métodos: 912 molares (456 primeros y 456 segundos molares) resultantes del análisis de 228 tomografías mandibulares fueron evaluados. Mediante una reconstrucción panorámica y cortes tomográficos axiales se estableció la configuración radicular, clasificando la presencia y tipo de conducto por medio del análisis de 5 cortes a lo largo de la raíz. Los datos fueron analizados estadísticamente con un intervalo de confianza del 5%. Resultados: De los 912 molares analizados, 70 fueron clasificados como conductos en forma de C (7.68%), correspondiendo al 58.33% de aquellos molares que presentaron raíces fusionadas. El 95.7% de esta configuración de conductos fue observada en segundos molares inferiores, presentándose con mayor frecuencia en mujeres (n=45, 64.29%). El 45.65% de los casos que presentaron conductos en C se manifestaron bilateralmente y la configuración más frecuente observada fue la C3 (n=401, 66.63%) según la clasificación de Melton. Conclusión: Los conductos en forma de C de los molares mandibulares en la población estudiada fueron observados principalmente en segundos molares, marcando una clara predilección por el sexo femenino y un alto porcentaje de bilateralidad. La presencia de raíces fusionadas aumenta significativamente la posibilidad de encontrar este tipo de configuración radicular.

Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile

Background: Acute myeloid leukemia (AML) is the most common leukemia in adults. Aim: To Describe our population of patients with AML and report the outcomes of our treatments. Material and Methods: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). Results: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. Conclusions: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

[Acute myeloid leukemia. Analysis of 114 patients]. / Actualización de resultados demográficos y terapéuticos de pacientes con Leucemia Mieloide Aguda no promielocítica en el Hospital Clínico de la Pontificia Universidad Católica de Chile.

BACKGROUND: Acute myeloid leukemia (AML) is the most common leukemia in adults. AIM: To Describe our population of patients with AML and report the outcomes of our treatments. MATERIAL AND METHODS: Review of electronic clinical records of 114 patients with AML with a median age of 57 years (59% men). RESULTS: Seventeen percent of patients were classified as low risk, 38% as intermediate risk and 33% as high risk. Seventy-six percent of patients were treated with intensive chemotherapy. Five years overall survival according to cytogenetic risk was 59, 41, and 12% in low, intermediate, and high-risk patients, respectively. The outcomes were better in patients under 60 years. The median survival of patients treated with intensive chemotherapy aged less than 60 years and 60 years and above was 3.4 and 1 year, respectively. CONCLUSIONS: Our results are comparable to those reported in developed countries. Improving the survival of patients 60 years and older is our main challenge.

[Dermatological manifestations of monoclonal gammopathies]. / Patologías cutáneas asociadas a gammapatías monoclonales: ¿qué sabemos hasta ahora?

Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.

Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma.

Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3ζ/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1-2 CRS at a median of 4 (range 3-7) days. There were no cases of grade ≥3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-γ, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.

[Age does not affect the outcome of allogeneic hematopoietic precursor transplantation for acute myeloid leukemia]. / Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda.

BACKGROUND: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. AIM: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. MATERIAL AND METHODS: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. RESULTS: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. CONCLUSIONS: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.

Ruxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids.

INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.

Patologías cutáneas asociadas a gammapatías monoclonales: ¿qué sabemos hasta ahora? / Dermatological manifestations of monoclonal gammopathies

Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.

Imaging the electrical activity of organelles in living cells.

Eukaryotic cells are complex systems compartmentalized in membrane-bound organelles. Visualization of organellar electrical activity in living cells requires both a suitable reporter and non-invasive imaging at high spatiotemporal resolution. Here we present hVoSorg, an optical method to monitor changes in the membrane potential of subcellular membranes. This method takes advantage of a FRET pair consisting of a membrane-bound voltage-insensitive fluorescent donor and a non-fluorescent voltage-dependent acceptor that rapidly moves across the membrane in response to changes in polarity. Compared to the currently available techniques, hVoSorg has advantages including simple and precise subcellular targeting, the ability to record from individual organelles, and the potential for optical multiplexing of organellar activity.

TRPM8 Channel Promotes the Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells.

Various families of ion channels have been characterized in mesenchymal stem cells (MSCs), including some members of transient receptor potential (TRP) channels family. TRP channels are involved in critical cellular processes as differentiation and cell proliferation. Here, we analyzed the expression of TRPM8 channel in human bone marrow MSCs (hBM-MSCs), and its relation with osteogenic differentiation. Patch-clamp recordings showed that hBM-MSCs expressed outwardly rectifying currents which were increased by exposure to 500 µM menthol and were partially inhibited by 10 µM of BCTC, a TRPM8 channels antagonist. Additionally, we have found the expression of TRPM8 by RT-PCR and western blot. We also explored the TRPM8 localization in hBM-MSCs by immunofluorescence using confocal microscopy. Remarkably, hBM-MSCs treatment with 100 µM of menthol or 10 µM of icilin, TRPM8 agonists, increases osteogenic differentiation. Conversely, 20 µM of BCTC, induced a decrease of osteogenic differentiation. These results suggest that TRPM8 channels are functionally active in hBM-MSCs and have a role in cell differentiation.

Resultados a largo plazo de una cohorte chilena: la edad del paciente no incide en el resultado del trasplante alogénico de precursores hematopoyéticos para leucemia mieloide aguda

Background: In our country, transplantation centers differ in the age limit for allogeneic hematopoietic transplantation (ALOHT). In our program, transplants with age- adjusted conditioning are performed in patients until 70 years old. Currently more than 60% of ALOHT reported to the Center for International Bone Marrow Transplantation Research (CIBMTR) are performed in patients older than 40 years. Aim: To report our experience with ALOHT in acute myelogenous leukemia (AML), analyzing patient age at transplantation in different periods and transplant results in different age groups. Material and Methods: A retrospective analysis of the database of adult hematopoietic transplants in AML patients was performed. Demographic data, disease characteristics, transplant data, survival and relapse times, and mortality were collected. Results: In our program, 1030 transplants were performed in adults and 119 ALOHT were performed in AML patients, between 1990 and 2020. The median age of patients in all periods was 41 years, (range 16-69). The median age was 33 and 45 years, in the periods 1990-2000 and 2000-2020 respectively (p < 0.01). Seventy-eight patients received myeloablative conditioning (median age 44 years) and 41 reduced intensity conditioning (median age 53 years). Five-year overall survival was 44.6% (confidence intervals (CI) 41-48). Non relapse mortality of all periods was 19% (CI 17 - 40%) and relapse rate was 17 % (CI 16-22). No difference in five years overall survival among patients younger than 40, 41 to 50 and over 51 years was observed. Conclusions: Overall Survival, non-relapse mortality and relapse rate were similar in younger and older patients in our program and similar to those previously reported in other centers.