[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.

Retrospective study of a serie of pterygoid implants.

BACKGROUND: This article aspires to show that pterygoid implants are a magnificent and viable alternative to other posterior implants of the maxilla, especially in cases of atrophy. MATERIAL AND METHODS: This study is based on a retrospective analysis of pterygoid implant data from 2003 to 2023, recollecting the following variables: year of placement, location, shape of the implant, diameter of the implant, length of the implant, torque of the implant, whether or not it was post-extraction, whether or not there was immediate loading, whether or not smoking was present (smoking habit), the brand of the implant and the success/survival or failure/non survival of the implant. RESULTS: The total of 178 pterygoid implants placed in the 113 patients eligible for the study was analysed by subgroups, with percentage of global success of 98.3% (3 failures). CONCLUSIONS: Pterygoid implants offer biomechanical and success/survival characteristics similar or superior to the so-called conventional implants and avoid a series of surgical and prosthodontic procedures more difficult than the ones required by other implants in many occasions.

Intra-islet glucagon signalling regulates beta-cell connectivity, first-phase insulin secretion and glucose homoeostasis.

OBJECTIVE: Type 2 diabetes (T2D) is characterised by the loss of first-phase insulin secretion. We studied mice with ß-cell selective loss of the glucagon receptor (Gcgrfl/fl X Ins-1Cre), to investigate the role of intra-islet glucagon receptor (GCGR) signalling on pan-islet [Ca2+]I activity and insulin secretion. METHODS: Metabolic profiling was conducted on Gcgrß-cell-/- and littermate controls. Crossing with GCaMP6f (STOP flox) animals further allowed for ß-cell specific expression of a fluorescent calcium indicator. These islets were functionally imaged in vitro and in vivo. Wild-type mice were transplanted with islets expressing GCaMP6f in ß-cells into the anterior eye chamber and placed on a high fat diet. Part of the cohort received a glucagon analogue (GCG-analogue) for 40 days and the control group were fed to achieve weight matching. Calcium imaging was performed regularly during the development of hyperglycaemia and in response to GCG-analogue treatment. RESULTS: Gcgrß-cell-/- mice exhibited higher glucose levels following intraperitoneal glucose challenge (control 12.7 mmol/L ± 0.6 vs. Gcgrß-cell-/- 15.4 mmol/L ± 0.0 at 15 min, p = 0.002); fasting glycaemia was not different to controls. In vitro, Gcgrß-cell-/- islets showed profound loss of pan-islet [Ca2+]I waves in response to glucose which was only partially rescued in vivo. Diet induced obesity and hyperglycaemia also resulted in a loss of co-ordinated [Ca2+]I waves in transplanted islets. This was reversed with GCG-analogue treatment, independently of weight-loss (n = 8). CONCLUSION: These data provide novel evidence for the role of intra-islet GCGR signalling in sustaining synchronised [Ca2+]I waves and support a possible therapeutic role for glucagonergic agents to restore the insulin secretory capacity lost in T2D.

Rechallenge in idiosyncratic drug-induced liver injury: An analysis of cases in two large prospective registries according to existing definitions.

INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.

Effect of cationic surfactant on the physicochemical and antibacterial properties of colloidal systems (emulsions and microemulsions).

Colloidal systems have been used to encapsulate, protect and release essential oils in mouthwashes. In this study, we investigated the effect of cetylpyridinium chloride (CPC) on the physicochemical properties and antimicrobial activity of oil-in-water colloidal systems containing tea tree oil (TTO) and the nonionic surfactant polysorbate 80. Our main aim was to evaluate whether CPC could improve the antimicrobial activity of TTO, since this activity is impaired when this essential oil is encapsulated with polysorbate 80. These systems were prepared with different amounts of TTO (0-0.5% w/w) and CPC (0-0.5% w/w), at a final concentration of 2% (w/w) polysorbate 80. Dynamic light scattering (DLS) results revealed the formation of oil-swollen micelles and oil droplets as a function of TTO concentration. Increases in CPC concentrations led to a reduction of around 88% in the mean diameter of oil-swollen micelles. Although this variation was of only 20% for the oil droplets, the samples appearance changed from turbid to transparent. The surface charge of colloidal structures was also markedly affected by the CPC as demonstrated by the transition in zeta potential from slightly negative to highly positive values. Electron paramagnetic resonance (EPR) studies showed that this transition is followed by significant increases in the fluidity of surfactant monolayer of both colloidal structures. The antimicrobial activity of colloidal systems was tested against a Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureaus) bacteria. Our results revealed that the inhibition of bacterial growth is observed for the same CPC concentration (0.05% w/w for E. coli and 0.3% w/w for S. aureus) regardless of TTO content. These findings suggest that TTO may not act as an active ingredient in polysorbate 80 containing mouthwashes.

Prótesis mitral mecánica disfuncionante: cuando el trombo sobre pannus dificulta el diagnóstico / Dysfunctioning mechanical mitral valve prosthesis: When thrombus over pannus makes hinders diagnosis

La obstrucción de una válvula protésica es una complicación rara pero que puede ser letal. Las causas más frecuentes son la formación de trombos y pannus, en ausencia de datos infecciosos. El diagnóstico no siempre es sencillo recurriendo a la realización de tomografía computarizada (TC) cardiaca, y en el 46-85% de los casos coexisten trombo y pannus, por lo que el diagnóstico se complica. Un diagnóstico rápido es esencial para evitar un desenlace fatal de esta patología, cuya mortalidad, a pesar de un tratamiento correcto, es elevada.(AU)

Prosthetic valve obstruction is a rare but potentially lethal complication. The most frequent causes are thrombus and pannus formation, in the absence of infectious data. Diagnosis is not always easy using cardiac CT scanning and in 46-85% of cases thrombus and pannus coexist, complicating the diagnosis. A rapid diagnosis is essential to avoid a fatal outcome of this pathology whose mortality, despite correct treatment, is high.(AU)

Dysfunctioning mechanical mitral valve prosthesis: When thrombus over pannus makes hinders diagnosis.

Prosthetic valve obstruction is a rare but potentially lethal complication. The most frequent causes are thrombus and pannus formation, in the absence of infectious data. Diagnosis is not always easy using cardiac CT scanning and in 46%-85% of cases thrombus and pannus coexist, complicating the diagnosis. A rapid diagnosis is essential to avoid a fatal outcome of this pathology whose mortality, despite correct treatment, is high.

Temporary work disability following trapezial resection and suspension arthroplasty for thumb carpometacarpal osteoarthritis. / Incapacidad laboral temporal tras cirugía de rizartrosis mediante trapecectomía y artroplastia de suspensión con sutura de alta resistencia.

PURPOSE: The aim of this study is to assess the time to return to work (TRW) in patients undergoing trapezial resection using the Mini TightRope® system at our center and to investigate factors that might delay return to work following this surgery. MATERIAL AND METHODS: A retrospective study was conducted on patients who underwent Trapezial resection and suspensionplasty using the Mini TightRope® system between 2015 and 2016, with a minimum one-year follow-up. Telephone interviews were conducted along with a review of medical records and radiology reports, as well as temporary work disability documents, collecting epidemiological and occupational data. Groups were compared based on age, gender, dominant hand, biomechanical occupational requirements of the patients, and whether they had experienced prior temporary work disability. RESULTS: A total of 36 patients (29 women and 7 men) with an average age of 55.7 years were included. The median time to return to work was 126 days. Self-employed workers re-entered the workforce 72 days earlier on average; workers who had experienced prior temporary work disability had a greater total temporary work disability duration and took 91 days longer to return to work compared to those who had not. CONCLUSIONS: Patients employed by others and those who had experienced prior temporary work disability before the surgery had longer temporary work disability periods. In our study, no differences were observed based on gender, dominant hand, or biomechanical work demands of the intervened patients.

Computed diffusion-weighted imaging in patients with transient neurovascular symptoms with and without ischemic infarction.

PURPOSE: Detection of ischemic lesions in patients with transient neurovascular symptoms is relevant for the estimation of the risk of a subsequent stroke and etiological classification. To improve detection rates, different technical approaches have been used, such as diffusion-weighted imaging (DWI) with high b-values or higher magnetic field strength. Here, we sought to investigate the value of computed DWI (cDWI) with high b-values in these patients. METHODS: From an MRI report database we identified patients with transient neurovascular symptoms who underwent repeated MRI including DWI. cDWI was calculated with a monoexponential model with high b-values (2000, 3000, and 4000 s/mm2) and compared to the routinely used standard DWI with regard to presence of ischemic lesions and lesion detectability. RESULT: Overall 33 patients with transient neurovascular symptoms (71 [IQR 57-83.5] years; 21 [63.6%] male) were included. On DWI, acute ischemic lesions were observed in 22 (78.6%). Acute ischemic lesions were observed in 17 (51.5%) patients on initial DWI, and in 26 (78.8%) patients on follow-up DWI. Lesion detectability was rated significantly better on cDWI at 2000s/mm2 compared to standard DWI. In 2 (9.1%) patients, cDWI at 2000s/mm2 revealed an acute ischemic lesion proven on follow-up standard DWI which was not detected with certainty on the initial standard DWI. CONCLUSION: cDWI might be a valuable addition to routinely acquired standard DWI in patients with transient neurovascular symptoms since its use might result in improved ischemic lesion detection. A b-value of 2000s/mm2 seems most promising for clinical practice.

Clinical Features and Voxel-Based-Symptom-Lesion Mapping of Silent Aspiration in Acute Infratentorial Stroke.

Post-stroke dysphagia (PSD) is a severe and common complication after ischemic stroke. The role of silent aspiration as an important contributing factor in the development of a dysphagia-associated complications, in particular aspiration-associated pneumonia has been insufficiently understood. The aim of this study was to investigate the characteristics and risk factors of silent aspiration in patients with acute infratentorial stroke by FEES and to identify culprit lesions in stroke patient with a high risk of silent aspiration via voxel-based-symptom-lesion mapping (VBS/ML). This study is a retrospective observational study based on a prospectively collected FEES and stroke database. Consecutive patient cases with acute ischemic infratentorial stroke and FEES examination between 2017 and 2022 were identified. Group allocation was performed based on PAS scores. Imaging analysis was performed by manual assignment and by VBS/ML. Group comparisons were performed to assess silent aspiration characteristics. Binary logistic regression analysis was performed to determine if baseline clinical, demographic, and imaging parameters were helpful in predicting silent aspiration in patients. In this study 84 patient cases with acute infratentorial stroke who underwent FEES examination were included. Patients were moderately affected at admission (mean NIH-SS score at admission 5.7 SD ± 4.7). Most lesions were found pontine. Overall 40.5% of patients suffered from silent aspiration, most frequently in case of bilateral lesions. Patients with silent aspiration had higher NIH-SS scores at admission (p < 0.05), had a more severe swallowing disorder (p < 0.05) and were 4.7 times more likely to develop post-stroke pneumonia. Patients who underwent FEES examination later than 72 h after symptom onset were significantly more likely to suffer from silent aspiration and to develop pneumonia compared to patients who underwent FEES examination within the first 72 h (p < 0.05). A binary logistic regression model identified NIH-SS at admission as a weak predictor of silent aspiration. Neither in manual assignment of the lesions to brain regions nor in voxel-wise statistic regression any specific region was useful in prediction of silent aspiration. Silent aspiration is common in patients with infratentorial stroke and contributes to the risk for pneumonia. Patients with silent aspiration are more severely affected by stroke, but cannot reliably be identified by NIH-SS at admission or lesion location. Patients suffering from acute infratentorial stroke should been screened and examined for PSD and silent aspiration.

The Adaptive, Pain Sensitive, and Global Symptoms Clusters: Evidence from a Patient-Based Study.

OBJECTIVES: The largest epidemiologic study conducted about painful temporomandibular disorders (pTMDs) to date identified 3 clusters of individuals with similar symptoms-adaptive, pain sensitive, and global symptoms-which hold promise as a means of personalizing pain care. Our goal was to compare the clinical and psychological characteristics that are consistent with a pTMD clinical examination among patients who are seeking care and assigned to the different clusters. METHODS: This cross-sectional study used data from the medical records of patients attending Duke Innovative Pain Therapies between August 2017 and April 2021 who received a pTMD diagnosis (i.e., myalgia) and consented to have their data used for research. Data included orofacial and pain-related measures, dental features, and psychological measures. We used the Rapid OPPERA Algorithm to assign clusters to patients and multinomial regression to determine the likelihood (odds ratios [OR] and 95% confidence intervals [CI]) of being assigned to the pain sensitive or global symptoms cluster attributed to each measure. RESULTS: In total, 131 patients were included in this study and assigned a cluster: adaptive (n = 54, 41.2%), pain sensitive (n = 49, 37.4%), and global symptoms (n = 28, 21.4%). The PS cluster displayed greater numbers of temporomandibular joint sites (OR, 1.29; 95% CI, 1.01 to 1.65) and masticatory (1.48; 1.19 to 1.83) and cervical (1.23; 1.09 to 1.39) muscles with pain evoked by palpation. The GS cluster displayed greater scores of pain catastrophizing (1.04; 1.01 to 1.06) and perceived stress (1.23; 1.03 to 1.46) and was more likely to report persistent pain (16.23; 1.92 to 137.1) of higher impact (1.43; 1.14 to 1.80). CONCLUSION: Our findings support that care-seeking patients with pTMDs who are assigned to the GS cluster display a poorer psychological profile, even though those assigned to the PS cluster display more measures consistent with orofacial pain. Findings also establish the PS cluster as a group that does not display psychological comorbidities despite being hypersensitive. KNOWLEDGE TRANSFER STATEMENT: This study informs clinicians that patients seeking care for painful temporomandibular disorders, in specific cases of myalgia, can be classified into 1 of 3 groups that display unique profiles of symptoms. Most importantly, it emphasizes the importance of examining patients with painful temporomandibular disorders in a holistic manner that includes assessing symptoms of psychological distress. Patients with greater psychological distress will likely benefit from multidisciplinary treatment strategies that may include psychological treatments.

Radiological-pathological correlation in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH): imaging and histopathology.

AIM: To review histologically confirmed diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) cases and carry out a detailed pathological-radiological correlation to see if computed tomography (CT) can be used to confidently identify DIPNECH. MATERIALS AND METHODS: Twenty-three histologically confirmed DIPNECH patients in the shared database of two NHS Trusts were reviewed. CT images were reviewed by two independent radiologists, each of them with >10 years of experience in thoracic imaging. All histological specimens were reviewed by a single pathologist with >25 years of experience. The diagnosis of DIPNECH was made according to the current World Health Organization (WHO) definition included in the WHO 2015 classification of pulmonary tumours. The results on histology were compared to the presence of nodules and air trapping on CT. Demographic information and, when available, molecular imaging studies and pulmonary function tests were also considered. RESULTS: There are prototypal clinical and radiological findings reflecting the presence of underlying histological DIPNECH: middle-aged women with multiple small and scattered nodules due to the clustering and proliferation of neuroendocrine cells. At least one larger, dominant, lung nodule reflecting a carcinoid tumour is very common and mosaic attenuation/air trapping is seen approximately in 50% of cases in inspiratory scans. Airflow obstruction is rarely associated with histological bronchial or peribronchial fibrosis, which suggests other mechanisms must be involved in its development. CONCLUSION: CT can be used to predict pathological DIPNECH in the appropriate clinical setting. It is important to consider DIPNECH to avoid overdiagnosis of more sinister conditions such as lung cancer or metastases.

Mucormicosis maxilofacial: a propósito de un caso / Maxillofacial mucormycosis: about a case

El tratamiento de las infecciones fúngicas invasivas, tanto la aspergilosis invasora como la mucormicosis supone un importante desafío clínico por el reducido número de agentes antifúngicos azólicos disponibles y por la gravedad clínica. Debido a esta elevada mortalidad, es necesario un diagnóstico temprano y un tratamiento agresivo, no sólo debe ser médico sino también quirúrgico. Presentamos un caso de mucormicosis maxilofacial en un paciente sin antecedentes clínicos de interés. Se trata de un paciente de 40 años con bultoma en región submandibular derecha de aparición más o menos súbita. Refiere parestesias en labio inferior hemilabio derecho con desviación del mismo a la derecha, de un año. Extracción del molar sin complicaciones aparentes. Los resultados de la primera biopsia muestran tejidos blandos con microorganismos micóticos compatibles con mucormicosis. En la exploración clínica se palpa inflamación a nivel de la zona submandibular derecha, no dolorosa. Resto: buen estado general. Comienza tratamiento con fluconazol, y posteriormente con isavuconazol durante 43 días. Los resultados de la segunda biopsia (junio-21): proceso linfoproliferativo B de alto grado compatible con linfoma difuso de células grandes B de centro germinal. Se realiza PET/TC compatible con infiltración ganglionar laterocervical derecha alta y submentoniana con probable afectación de partes blandas y más dudosa amigdalar palatina bilateral de su proceso linfoproliferativo de base. En enero-22: estudio PET/CT que muestra respuesta metabólica completa (Deauville 1) de su proceso linfoproliferativo de base. (AU)

The treatment of invasive fungal infections, both invasive aspergillosis and mucormycosis, represents an important clinical challenge due to the small number of available azole antifungal agents and the clinical severity. Due to this high mortality, early diagnosis and aggressive treatment are necessary, not only medical but also surgical. We present a case of maxillofacial mucormycosis in a patient with no clinical history of interest. This is a 40-year-old patient with a lump in the right submandibular region of more or less sudden onset. Refers paresthesias in the lower lip right hemilip with deviation of the same to the right of a year. Molar extraction without apparent complications. The results of the first biopsy show soft tissues with fungal organisms consistent with mucormycosis. In the clinical examination, inflammation was palpated at the level of the right submandibular area, which was not painful. Rest: good general condition. He begins treatment with fluconazole, and later with isavuconazole for 43 days. The results of the second biopsy (June 21): high-grade B-lymphoproliferative process compatible with diffuse large B-cell lymphoma of the germinal center. PET/CT compatible with high right laterocervical and submental lymph node infiltration with probable soft tissue involvement and more doubtful bilateral palatine tonsillar involvement of its underlying lymphoproliferative process was performed. On January-22: PET/CT study showing complete metabolic response (Deauville 1) of his underlying lymphoproliferative process. (AU)

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

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.(AU)

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

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.(AU)

Review of the Greening Reaction by Thermal Treatment: New Insights Exploring the Structural Implications of Myoglobin.

Myoglobin is the main factor responsible for muscle pigmentation in tuna; muscle color depends upon changes in the oxidative state of myoglobin. The tuna industry has reported muscle greening after thermal treatment involving metmyoglobin (MetMb), trimethylamine oxide (TMAO), and free cysteine (Cys). It has been proposed that this pigmentation change is due to a disulfide bond between a unique cysteine residue (Cys10) found in tuna MetMb and free Cys. However, no evidence has been given to confirm that this reaction occurs. In this review, new findings about the mechanism of this greening reaction are discussed, showing evidence of how free radicals produced from Cys oxidation under thermal treatment participate in the greening of tuna and horse muscle during thermal treatment. In addition, the reaction conditions are compared to other green myoglobins, such as sulfmyoglobin, verdomyoglobin, and cholemyoglobin.