Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Influence of general anaesthesia on the intravenous acetaminophen pharmacokinetics in Beagle dogs.

OBJECTIVE: To determine if general anaesthesia influences the intravenous (IV) pharmacokinetics (PK) of acetaminophen in dogs. STUDY DESIGN: Prospective, crossover, randomized experimental study. ANIMALS: A group of nine healthy Beagle dogs. METHODS: Acetaminophen PK were determined in conscious and anaesthetized dogs on two separate occasions. Blood samples were collected before, and at 5, 10, 15, 30, 45, 60 and 90 minutes and 2, 3, 4, 6, 8, 12 and 24 hours after 20 mg kg-1 IV acetaminophen administration. Haematocrit, total proteins, albumin, alanine aminotransferase, aspartate aminotransferase, urea and creatinine were determined at baseline and 24 hours after acetaminophen. The anaesthetized group underwent general anaesthesia (90 minutes) for dental cleaning. After the administration of dexmedetomidine (3 µg kg-1) intramuscularly, anaesthesia was induced with propofol (2-3 mg kg-1) IV, followed by acetaminophen administration. Anaesthesia was maintained with isoflurane in 50% oxygen (Fe'Iso 1.3-1.5%). Dogs were mechanically ventilated. Plasma concentrations were analysed with high-performance liquid chromatography. PK analysis was undertaken using compartmental modelling. A Wilcoxon test was used to compare PK data between groups, and clinical laboratory values between groups, and before versus 24 hours after acetaminophen administration. Data are presented as median and range (p < 0.05). RESULTS: A two-compartmental model best described time-concentration profiles of acetaminophen. No significant differences were found for volume of distribution values 1.41 (0.94-3.65) and 1.72 (0.89-2.60) L kg-1, clearance values 1.52 (0.71-2.30) and 1.60 (0.91-1.78) L kg-1 hour-1 or terminal elimination half-life values 2.45 (1.45-8.71) and 3.57 (1.96-6.35) hours between conscious and anaesthetized dogs, respectively. Clinical laboratory variables were within normal range. No adverse effects were recorded. CONCLUSIONS AND CLINICAL RELEVANCE: IV acetaminophen PK in healthy Beagle dogs were unaffected by general anaesthesia under the study conditions. Further studies are necessary to evaluate the PK in different clinical contexts.

The viscosity of dilute carbon nanotube (1D) and graphene oxide (2D) nanofluids.

Controlling the physicochemical properties of nanoparticles in fluids directly impacts on their liquid phase processing and applications in nanofluidics, thermal engineering, biomedicine and printed electronics. In this work, the temperature dependent viscosity of various aqueous nanofluids containing carbon nanotubes (CNTs) or graphene oxide (GO), i.e. 1D and 2D nanoparticles with extreme aspect ratios, is analyzed by empirical and predictive physical models. The focus is to understand how the nanoparticle shape, concentration, motion degrees and surface chemistry affect the viscosity of diluted dispersions. To this end, experimental results from capillary viscosimeters are first examined in terms of the energy of viscous flow and the maximum packing fraction applying the Maron-Pierce model. Next, a comparison of the experimental data with predictive physical models is carried out in terms of nanoparticle characteristics that affect the viscosity of the fluid, mostly their aspect ratio. The analysis of intrinsic viscosity data leads to a general understanding of motion modes for carbon nanoparticles, including those with extreme aspect ratios, in a flowing liquid. The resulting universal curve might be extended to the prediction of the viscosity for any kind of 1D and 2D nanoparticles in dilute suspensions.

Neurofilament light chain levels in pregnant multiple sclerosis patients: a prospective cohort study.

BACKGROUND AND PURPOSE: Neurofilament light chain is a cytoskeletal protein of neurons. Its levels are increasingly recognized as measures of neuroaxonal damage. The aim of this study was to explore serum neurofilament light chain (sNfL) levels in multiple sclerosis (MS) patients and healthy controls during pregnancy and puerperium. METHODS: This was a prospective, longitudinal, single-center study. sNfL concentration was assessed using a highly sensitive single-molecule array during pregnancy and in puerperium, in a cohort of 39 pregnant patients with relapsing multiple sclerosis (P-MS). Twenty-one healthy pregnant women (HPW) served as a control group. Eight P-MS suffered relapses during pregnancy (P-MS-R) in the first or second trimesters. RESULTS: No differences in pregnancy and delivery data were observed between P-MS and HPW. P-MS showed higher sNfL values than HPW in the first trimester, independently of the presence (P = 0.002) or not (P = 0.02) of relapses during pregnancy. However, in the third trimester, only P-MS-R showed higher sNfL values than HPW (P = 0.001). These differences extended to the puerperium, where P-MS-R showed higher sNfL values than those with no relapses during gestation (P = 0.02). CONCLUSION: These data strongly suggest that sNfL levels reflect MS activity during pregnancy. Additionally, the absence of relapses during pregnancy may have a beneficial effect on neurodegeneration during puerperium.

Genes differentially expressed by methylprednisolone in vivo in CD4 T lymphocytes from multiple sclerosis patients: potential biomarkers.

Intravenous methylprednisolone (IVMP) is the gold standard treatment in acute relapses of multiple sclerosis. Knowing the response to IVMP in advance could facilitate earlier selection of patients for subsequent courses of therapy. However, molecular mechanisms and changes in gene expression induced by methylprednisolone remain unknown. The aim of the study was to identify in vivo differentially expressed genes in relapsing-remitting multiple sclerosis patients after 3-6 days of treatment with IVMP. For this purpose, whole-genome transcription profiling of CD4+ T lymphocytes was performed before and after treatment with IVMP in 8 relapsing-remitting multiple sclerosis patients during relapse using Human GE 4x44K v2 microarrays. Differentially expressed genes were identified using a paired t test on GeneSpring v13.0 software. A P-value <0.001 and a twofold change were considered significant. Microarray data were confirmed using real-time PCR. Microarray revealed changes in gene expression: four genes were downregulated (B3GNT3, ZNF683, IFNG and TNF) and seven upregulated (DEFA4, CTSG, DEFA8P, AZU1, MPO, ELANE and PRTN3). Pathway analysis revealed the transforming growth factor-ß signaling pathway to be affected. Comparison with previously published data on in vitro methylprednisolone-regulated genes showed that SMAD7, TNF and CHI3L1 were also downregulated in vivo in relapsing-remitting multiple sclerosis patients. In summary, we performed the first in vivo transcriptome analysis in CD4+ T lymphocytes before and after the treatment with IVMP in patients with multiple sclerosis. Identification of differentially expressed genes in patients receiving IVMP could improve our understanding of the molecular mechanisms underlying the therapeutic effects of IVMP and highlight potential biomarkers of the response to IVMP.

Study of the possible link of 25-hydroxyvitamin D with Epstein-Barr virus and human herpesvirus 6 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Although the causes of multiple sclerosis (MS) remain partially unknown, environmental and genetic factors are thought to play a role in its aetiopathogenesis. Hypovitaminosis D, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) infections have been described as possible MS triggers. Our aim was to analyse the possible link between 25-hydroxyvitamin D [25(OH)D] and viruses in patients with MS. METHODS: We included 482 patients with MS in a 2-year study. Serum samples were collected to analyse 25(OH)D levels and, according to sample availability, antibody titres against EBV and HHV-6 by enzyme-linked immunosorbent assay. DNA was extracted from blood in order to analyse EBV and HHV-6 viral load by quantitative real-time polymerase chain reaction and to genotype MS-related single nucleotide polymorphisms (rs3135388, rs2248359 and rs12368653) when possible. RESULTS: The 25(OH)D levels were significantly higher in the first semester of the year than in the second. Carriers of the risk allele rs2248359-C showed lower 25(OH)D levels than non-carriers. For EBV, viral load was significantly higher when 25(OH)D levels were low, demonstrating an inverse correlation between 25(OH)D levels and EBV load. CONCLUSIONS: The 25(OH)D levels could be involved in the regulation of EBV replication/reactivation in patients with MS.

Effect of carbon sources on the growth and ethanol production of native yeast Pichia kudriavzevii ITV-S42 isolated from sweet sorghum juice.

The importance of non-Saccharomyces yeast species in fermentation processes is widely acknowledged. Within this group, Pichia kudriavzevii ITV-S42 yeast strain shows particularly desirable characteristics for ethanol production. Despite this fact, a thorough study of the metabolic and kinetic characteristics of this strain is currently unavailable. The aim of this work is to study the nutritional requirements of Pichia kudriavzevii ITV-S42 strain and the effect of different carbon sources on the growth and ethanol production. Results showed that glucose and fructose were both assimilated and fermented, achieving biomass and ethanol yields of 0.37 and 0.32 gg-1, respectively. Glycerol was assimilated but not fermented; achieving a biomass yield of 0.88 gg-1. Xylose and sucrose were not metabolized by the yeast strain. Finally, the use of a culture medium enriched with salts and yeast extract favored glucose consumption both for growth and ethanol production, improving ethanol tolerance reported for this genre (35 g L-1) to 90 g L-1 maximum ethanol concentration (over 100%). Furthermore Pichia kudriavzevii ITV-S42 maintained its fermentative capacity up to 200 g L-1 initial glucose, demonstrating that this yeast is osmotolerant.

Migraine education brochures and patient-perceived satisfaction.

INTRODUCTION: Brochures are commonly used as educational tools in daily neurological practice. They are provided to increase the general population's knowledge of a specific disease and also to combat sources of erroneous information. Surveys are the most commonly used method of ascertaining user satisfaction with services received. OBJECTIVES: This study will assess patient-perceived satisfaction and provide feedback to measure the comprehensibility and overall utility of an educational brochure on migraine. MATERIAL AND METHODS: Open prospective multicentre study of a group of patients diagnosed with migraine in neurology clinics in Alicante province. During the initial visit, each patient received a migraine brochure prepared by the Valencian Society of Neurology's study group for headaches (CEFALIC). During a follow-up visit, they were then asked to fill out a personal survey on the overall quality of the information in the brochure. RESULTS: We included a total of 257 patients diagnosed with migraine (83% episodic migraine; 17% chronic migraine); mean age was 37.6 years. Two hundred seven patients confirmed having read the brochure (80.5%); 50 patients (19.5%) either forgot to read it or had no interest in doing so. The brochure seemed interesting and easy to understand according to 90% of the patients. Seventy-six per cent of the respondents stated that reading the brochure increased their overall knowledge of migraine, while 50% of the patients found the brochure useful for improving migraine control. CONCLUSIONS: Patients found the migraine educational brochure to be comprehensible, a means of increasing overall knowledge of the disease, and useful for increasing control over migraines. Evaluations of the educational brochures that we provide to our patients with migraine should be studied to discover the causes of dissatisfaction, determine the level of quality of service, and investigate potential areas for improvement.

Mitochondrial adaptations evoked with exercise are associated with a reduction in age-induced testicular atrophy in Fischer-344 rats.

Mitochondrial dysfunction in various tissues has been associated with numerous conditions including aging. In testes, aging induces atrophy and a decline in male reproductive function but the involvement of mitochondria is not clear. The purpose of this study was to examine whether the mitochondrial profile differed with (1) aging, and (2) 10-weeks of treadmill exercise training, in the testes of young (6 month) and old (24 month) Fischer-344 (F344) animals. Old animals exhibited significant atrophy (30 % decline; P < 0.05) in testes compared to young animals. However, relative mitochondrial content was not reduced with age and this was consistent with the lack of change in the mitochondrial biogenesis regulator protein, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and its downstream targets nuclear respiratory factor-1 and mitochondrial transcription factor A. No effect was observed in the pro- or anti-apoptotic proteins, Bax and Bcl-2, respectively, but age increased apoptosis inducing factor levels. Endurance training induced beneficial mitochondrial adaptations that were more prominent in old animals including greater increases in relative mtDNA content, biogenesis/remodeling (mitofusin 2), antioxidant capacity (mitochondrial superoxide dismutase) and lower levels of phosphorylated histone H2AX, an early marker of DNA damage (P < 0.05). Importantly, these exercise-induced changes were associated with an attenuation of testes atrophy in older sedentary animals (P < 0.05). Our results indicate that aging-induced atrophy in testes may not be associated with changes in relative mitochondrial content and key regulatory proteins and that exercise started in late-life elicits beneficial changes in mitochondria that may protect against age-induced testicular atrophy.

Large artery occlusion diagnosed by computed tomography angiography in acute ischaemic stroke: frequency, predictive factors, and safety.

INTRODUCTION: Demonstrating artery occlusion in ischaemic stroke has gained importance due to the increasing availability of endovascular therapies. This study evaluates the frequency of artery occlusion, its associated factors, and complications following the use of CT-angiography in acute stroke. METHODS: We retrospectively analysed a cohort of patients who suffered acute ischaemic stroke between July and-December 2011. RESULTS: We included 157 patients (mean age, 74±11; mean NIHSS score, 5 [2-13]). Of that total, 56.7% of the patients were admitted to hospital during the first 8hours. CT-angiography was performed in 71 cases (45.2%); arterial large-vessel occlusion was detected in 37 (52.1%) of these cases, and the most frequent site was M1 (40%). Univariate analysis showed that the NIHSS score (17 vs 7, P<.001) and atrial fibrillation (64% vs 32%, P=.006) were associated with artery occlusion. A logistic regression analysis was performed subsequently, confirming these associations. There were no cases of contrast-induced nephropathy. Door-to-needle time for intravenous thrombolysis was 61.2±24.5minutes in patients who underwent CT-angiography, and 53.5±34.3minutes in those who did not (P=.495). CONCLUSIONS: Arterial occlusions are seen in 23.6% of patients, especially in those who are admitted during the first few hours. NIHSS score serves as a useful predictive factor.

[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (II)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).

The XVI Post-ECTRIMS meeting was held in Seville on 20 and 21 October 2023, where expert neurologists in multiple sclerosis (MS) summarised the main new developments presented at the ECTRIMS 2023 congress, which took place in Milan from 11 to 13 October. The aim of this article is to summarise the content presented at the Post-ECTRIMS Meeting, in an article in two parts. This second part covers the health of women and elderly MS patients, new trends in the treatment of cognitive impairment, focusing particularly on meditation, neuroeducation and cognitive rehabilitation, and introduces the concept of fatigability, which has been used to a limited extent in MS. The key role of digitalization and artificial intelligence in the theoretically near future is subject to debate, along with the potential these technologies can offer. The most recent research on the various treatment algorithms and their efficacy and safety in the management of the disease is reviewed. Finally, the most relevant data for cladribine and evobrutinib are presented, as well as future therapeutic strategies currently being investigated.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (II).Los días 20 y 21 de octubre se celebró en Sevilla la XVI edición de la reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso del ECTRIMS 2023, celebrado en Milán del 11 al 13 de octubre. El objetivo de este artículo es sintetizar las ponencias que tuvieron lugar en la reunión Post-ECTRIMS en un artículo desglosado en dos partes. En esta segunda parte se abordan la salud de la mujer y del paciente mayor con EM, las nuevas tendencias en el tratamiento del deterioro cognitivo, con especial mención a la meditación, la neuroeducación y la rehabilitación cognitiva, y se introduce el concepto de fatigabilidad, poco utilizado en la EM. El papel clave de la digitalización y la inteligencia artificial en un futuro teóricamente cercano es objeto de debate, junto con las expectativas que pueden ofrecer. Se repasa la investigación más reciente sobre los distintos algoritmos de tratamiento, y su eficacia y seguridad en el manejo de la enfermedad. Por último, se exponen los datos más relevantes sobre la cladribina y el evobrutinib, y se presentan las futuras estrategias terapéuticas actualmente en investigación.

The estimation of visceral adipose tissue with a body composition monitor predicts the metabolic syndrome.

BACKGROUND: Central obesity has a higher risk of the metabolic syndrome (MetS) and cardiovascular diseases. It is estimated by measuring waist circumference (WC) and waist-to-hip ratio (WHR), which are operator-dependent. The present study aimed to validate a body composition monitor (BCM) as a tool for estimating visceral adipose tissue (VAT), as well as to assess its capacity to predict the MetS and its correlation with anthropometric parameters. METHODS: We measured WC, WHR and body mass index (BMI) in 60 recruited subjects. BCM estimated VAT (1-30 points). Body composition and resting energy expenditure (REE) were compared with bioelectrical impedance analysis (BIA) and indirect calorimetry, respectively. VAT was estimated by BCM (range 1-30 points), We evaluated the capability of VAT, WC, BMI and WHR to predict the MetS by ATP-III criteria. RESULTS: The mean (SD) age of subjects was 36.8 (12.9) years, 80% were female, and 47% had the MetS. Body composition and REE estimated by BCM had a significant correlation with BIA (r = 0.85-0.91, P< 0.001) and REE (r = 0.86, P < 0.001), respectively, even after adjusting by sex. VAT estimation by BCM was positively correlated with WC (r = 0.75, P< 0.001) and WHR (r = 0.61, P < 0.001). The area under the receiver operator characteristic curves to predict the MetS was 0.93 for VAT, 0.81 for WC, 0.76 for WHR and 0.74 for BMI. VAT ≥10 points had a sensitivity of 100% and a specificity of 82% for predicting the MetS. CONCLUSIONS: VAT estimation by BCM efficiently predicts the MetS and correlates with anthropometric parameters of central obesity. Its routine use could facilitate cardiovascular risk estimation and follow-up in overweight and obese patients in ambulatory practice.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

Tailored SWCNT functionalization optimized for compatibility with epoxy matrices.

We have modified single walled carbon nanotubes (SWCNTs) with well defined matrix-based architectures to improve interface interaction in SWCNT/epoxy composites. The hardener and two pre-synthesized oligomers containing epoxy and hardener moieties were covalently attached to the SWCNT walls by in situ diazonium or carboxylic coupling reactions. In this way, SWCNTs bearing amine or epoxide-terminated fragments of different molecular weights, which resemble the chemical structure of the cured resin, were synthesized. A combination of characterization techniques such as Raman and infrared absorption (FTIR) spectroscopy, elemental analysis and coupled thermogravimetry-FTIR spectroscopy were used to identify both the functional groups and degree of functionalization of SWCNTs synthesized by the laser ablation and arc-discharge methods. Depending on the type of reaction employed for the chemical functionalization and the molecular weight of the attached fragment, it was possible to control the degree of functionalization and the electronic properties of the functionalized SWCNTs. Improved dispersion of SWCNTs in the epoxy matrix was achieved by direct integration without using solvents, as observed from optical microscopy and rheology measurements of the SWCNT/epoxy mixtures. Composite materials using these fillers are expected to exhibit improved properties while preserving the thermosetting architecture.

[Recurrent acute rhombencephalomyelitis in an adult or neuromyelitis optica? Presentation of a case]. / ¿Rombencefalomielitis aguda recurrente del adulto o neuromielitis óptica? A propósito de un caso.

INTRODUCTION: The lack of accepted homogeneous criteria for the definition of some demyelinating diseases makes diagnostic characterization difficult and limits data interpretation and therapeutic recommendations. Recurrent encephalomyelitis (ADE-R) along with borderline cases of neuromyelitis optica (NMO) are especially controversial. OBJECTIVE: To describe the clinical and radiological evolution of an adult-onset ADE-R versus NMO case throughout 9 years of follow-up. PATIENT AND METHODS: Our patient presented with severe symptoms of rhombencephalomyelitis and the cranial and spinal magnetic resonance imaging (MRI) showed large lesions, with gadolinium enhancement in brainstem and spinal cord, correlating with the clinical picture. Infectious aetiology was excluded, IgG index was normal and NMO antibodies were negative. After treatment with intravenous corticosteroids and plasmapheresis, there was excellent recovery in the acute phase. During follow-up, seven relapses have occurred, mainly in the spinal cord, with good recovery and the same symptomatology, albeit with different severity. Immunosuppressive treatment was introduced since the beginning. CONCLUSIONS: Our case shares common features of both ADE-R and NMO, illustrating that diagnostic characterization is not easy in spite of current criteria.

[Functional results after shoulder hemiarthroplasty for proximal humerus fracture: experience in our center]. / Resultados funcionales tras hemiartroplastía de hombro por fractura de húmero proximal: experiencia en nuestro centro.

INTRODUCTION: shoulder hemiarthroplasty is being relegated as a treatment for non-osteosynthetic proximal humerus fractures. Our objective is to analyze the functional results of patients treated with hemiarthroplasty for this reason in our hospital. MATERIAL AND METHODS: cross-sectional descriptive study that includes patients operated between February 2016 and November 2021; 24 patients, with an average follow-up of 44.6 months. Active joint balance, the Constant-Murley test, the DASH questionnaire and current pain (VAS) were collected. The radiographic parameters analyzed were the number of fracture fragments and the consolidation of the tuberosities. RESULTS: a mean of 71.65 ± 13.75 was obtained in the Constant-Murley and 18.14% ± 13.92 in the DASH. For shoulder flexion, the mean was 108.75° ± 41.26; 104.5° ± 43.68 for abduction and 33° ± 14.73 for external rotation. About internal rotation, 60% of the patients reached the scapular plane. Average VAS was 1.25 ± 1.74. Consolidated tuberosities in 90.5%. There were no significant differences comparing the Constant-Murley test, DASH or rotations between both, over and under 65 years old group of patients. Those over 65 years of age obtained a mean flexion of 125.91° ± 26.82 whereas those under 87.78° ± 26.82 (p = 0.038). The mean abduction in those over 65 was 125.45 ± 28.94 vs 78.89 ± 46.29 in the young group (p = 0.012). CONCLUSION: hemiarthroplasty provides quality of life with acceptable functionality and good pain control, therefore it should continue to be an alternative to consider in selected patients.

INTRODUCCIÓN: la hemiartroplastía de hombro está siendo relegada como tratamiento de fracturas de húmero proximal no osteosintetizables. Nuestro objetivo es analizar los resultados funcionales de los pacientes tratados con hemiartroplastía por este motivo en nuestro centro. MATERIAL Y MÉTODOS: estudio descriptivo transversal que incluye a los pacientes intervenidos entre Febrero de 2016 y Noviembre de 2021; 24 pacientes, con un seguimiento medio de 44.6 meses. Fueron recogidos el balance articular activo, el test de Constant-Murley, el cuestionario DASH y el dolor actual (EVA). Como parámetros radiográficos se analizó el número de fragmentos de fractura y la consolidación de las tuberosidades. RESULTADOS: se obtuvo una media de 71.65 ± 13.75 en el Constant-Murley y de 18.14% ± 13.92 en el DASH. Para flexión de hombro la media fue de 108.75° ± 41.26; 104.5° ± 43.68 para abducción y 33° ± 14.73 para rotación externa. En rotación interna 60% llegaba hasta plano interescapular. EVA medio de 1.25 ± 1.74. Tuberosidades consolidadas en 90.5%. No hubo diferencias significativas entre el Constant-Murley, DASH ni rotaciones de pacientes mayores y menores de 65 años. Los mayores de 65 años obtuvieron flexión media de 125.91° ± 26.82 y los menores de 87.78° ± 26.82 (p = 0.038). La abducción media en mayores de 65 fue de 125.45 ± 28.94 versus 78.89 ± 46.29 en el grupo joven (p = 0.012). CONCLUSIÓN: la hemiartroplastía otorga calidad de vida con aceptable funcionalidad y buen control del dolor, por lo que debe continuar siendo una alternativa a tener en cuenta en pacientes seleccionados.