On the origin of optical rotation changes during the κ-carrageenan disorder-to-order transition.

It is well established that solutions of both polymeric and oligomeric κ-carrageenan exhibit a clear change in optical rotation (OR), in concert with gel-formation for polymeric samples, as the solution is cooled in the presence of certain ions. The canonical interpretation - that this OR change reflects a 'coil-to-helix transition' in single chains - has seemed unambiguous; the solution- or 'disordered'-state structure has ubiquitously been assumed to be a 'random coil', and the helical nature of carrageenan in the solid-state was settled in the 1970s. However, recent work has found that κ-carrageenan contains substantial helical secondary structure elements in the disordered-state, raising doubts over the validity of this interpretation. To investigate the origins of the OR, density-functional theory calculations were conducted using atomic models of κ-carrageenan oligomers. Changes were found to occur in the predicted OR owing purely to dimerization of chains, and - together with the additional effects of slight changes in conformation that occur when separated helical chains form double-helices - the predicted OR changes are qualitatively consistent with experimental results. These findings contribute to a growing body of evidence that the carrageenan 'disorder-to-order' transition is a cooperative process, and have further implications for the interpretation of OR changes demonstrated by macromolecules in general.

Mixed-Valence Tetrametallic Iridium Chains.

Neutral [X-{Ir2 }-{Ir2 }-X] (X=Cl, Br, SCN, I) and dicationic [L-{Ir2 }-{Ir2 }-L]2+ (L=MeCN, Me2 CO) tetrametallic iridium chains made by connecting two dinuclear {Ir2 } units ({Ir2 }=[Ir2 (µ-OPy)2 (CO)4 ], OPy=2-pyridonate) by an iridium-iridium bond are described. The complexes exhibit fractional averaged oxidation states of +1.5 and electronic delocalization along the metallic chain. While the axial ligands do not significantly affect the metal-metal bond lengths, the metallic chain has a significant impact on the iridium-L/X bond distances. The complexes show free rotation around the unsupported iridium-iridium bond in solution, with a low-energy transition state for the chloride chain. The absorption spectra of these complexes show characteristic bands at 438-504 nm, which can be fine-tuned by varying the terminal capping ligands.

Audiological phenotyping evaluation in KBG syndrome: Description of a multicenter review.

OBJECTIVES: Our objective was to reinforce clinical knowledge of hearing impairment in KBG syndrome. KBG syndrome is a rare genetic disorder due to monoallelic pathogenic variations of ANKRD11.The typical phenotype includes facial dysmorphism, costal and spinal malformation and developmental delay. Hearing loss in KBG patients has been reported for many years, but no study has evaluated audiological phenotyping from a clinical and an anatomical point of view. METHODS: This French multicenter study included 32 KBG patients with retrospective collection of data on audiological features, ear imaging and genetic investigations. RESULTS: We identified a typical audiological profil in KBG syndrome: conductive (71%), bilateral (81%), mild to moderate (84%) and stable (69%) hearing loss, with some audiological heterogeneity. Among patients with an abnormality on CT imaging (55%), ossicular chain impairment (67%), fixation of the stapes footplate (33%) and inner-ear malformations (33%) were the most common abnormalities. CONCLUSION: We recommend a complete audiological and radiological evaluation and an ENT-follow up in all patients presenting with KBG Syndrome. Imaging evaluation is necessary to determine the nature of lesions in the middle and inner ear.

Iridium-Catalyzed Regio- and Diastereoselective Synthesis of C-Substituted Piperazines.

Piperazine rings are essential motifs frequently found in commercial drugs. However, synthetic methodologies are mainly limited to N-substituted piperazines, preventing structural diversity. Disclosed herein is a straightforward catalytic method for the synthesis of complex C-substituted piperazines based on an uncommon head-to-head coupling of easily prepared imines. This 100% atom-economic process allows the selective formation of a sole diastereoisomer, a broad substrate scope, and a good functional group tolerance employing a bench-stable iridium catalyst under mild reaction conditions. Key to the success is the addition of N-oxides to the reaction mixture, as they notably enhance the catalytic activity and selectivity.

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

Kikuchi-Fujimoto Disease and COVID-19 vaccination: pharmacovigilance approach.

Summary: Background. Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually presented as painful cervical nodes and associated with fever, headache, night sweats, nausea, vomiting and sore throat. Etiology of KFD is still unclear, two theories have been proposed: infections and autoimmune origin. Due to recent reports of KFD related to COVID-19 vaccination, the novelty of the mechanism of these vaccines and the immunomodulated role of both matters, a literature and adverse event databases review was carried out in order to shed light on the relationship between these two matters. Methods. A search in the Spanish and the European adverse events databases (FEDRA and Eudravigilance) was performed. Search criteria were any drug and the diagnosis "Histiocytic necrotizing lymphadenitis" according to the Medical Dictionary for Medical Activities version 25.0. All adverse events registered as June 2, 2022, were included. Results. FEDRA encompassed two KFD reports, one related to a mRNA COVID-19 vaccine. Eudravigilance included a total of 62 KFD cases, 14 of them associated to COVID-19 vaccines and eight to other vaccines. Conclusions. Pharmacovigilance is of utter importance in detecting adverse events caused by new vaccines. More research is needed to establish a final connection between KFD and COVD-19 vaccines, but due to the physiopathology of the condition, how vaccines stimulate the immune system and the high number of reported KFD cases with vaccines given its rare incidence, it is plausible to think that both entities are related.

Kinetics of response to iloprost evaluated by laser speckle contrast analysis in systemic sclerosis.

OBJECTIVE: Iloprost (ILO) is recommended for the treatment of systemic sclerosis (SSc) microangiopathy, but there is no common consensus on its optimal dosage. The aim of this study is to evaluate the kinetics of response to ILO administered in a daily outpatient scheme in SSc subjects using laser speckle contrast analysis (LASCA). METHOD: Adult SSc patients in stable therapy with ILO administered for 6 h for 2 consecutive days every 4 weeks were enrolled. Peripheral finger perfusion was assessed by LASCA. Each patient underwent five LASCA evaluations: before and after each day of ILO (D1pre, D1post, D2pre, and D2post) and after 4 weeks (D30). RESULTS: Twenty-seven SSc patients (77.8% female, mean age 61.5 years) were enrolled. LASCA showed an increase in perfusion at the end of each ILO course, but on the second day (both D1pre vs D2pre and D2pre vs D2post) the increase was no longer significant in half of the fingers. Moreover, compared to D1post, at the beginning of the second ILO day most of the fingers had already shown a significant reduction in perfusion. After 1 month, there were no statistically significant differences between the perfusion values of D1pre and D30. CONCLUSION: This LASCA study highlights the transience of the vasoactive effect of ILO, with a perfusion benefit that is completely lost after 1 month. The brevity of the perfusion effect of ILO and the use of LASCA are elements to consider in the design of future SSc trials to determine the optimal ILO dosage.

Ambiente matemático de niños y niñas chilenos: Factores que explican las actividades matemáticas en el hogar / Home math environment of Chilean boys and girls: Factors that explain home math activities

Resumen Introducción: el estudio analizó (a) las diferencias entre madres y padres en sus actividades matemáticas en el hogar y en otros factores del ambiente matemático (actitudes, ansiedad, creencias y expectativas matemáticas) y (b) la asociación entre los factores del ambiente matemático y las actividades matemáticas en el hogar. Método: participaron 266 familias de niños y niñas chilenos de primer a tercer grado de primaria (edad promedio = 93.35 meses, DE = 11.45 meses). Ambos padres contestaron un cuestionario sobre matemáticas en el hogar. Resultados: las madres reportaron realizar actividades matemáticas con mayor frecuencia que los padres. Análisis de ecuaciones estructurales mostraron que las actividades matemáticas realizadas por los padres se relacionaron con sus creencias, actitudes y expectativas matemáticas; mientras que las de las madres se relacionaron con sus creencias, actitudes y género de los niños. Conclusiones: los hallazgos aportan a la comprensión del ambiente matemático en el hogar.

Abstract Introduction: The study analyzes (a) the differences between mothers and fathers in their home math activities and home math environment factors (math attitudes, anxiety, beliefs, and expectations) and (b) the associations among the home math environment factors and home math activities of Chilean families. Method: Participants were 266 families of boys and girls attending grades 1-3 (mean age = 93.35 months, DS = 11.45 months). Both parents of each child independently answered a home math questionnaire. Results: Mothers reported doing more math activities with their children than fathers. The structural equation model analyses showed that the frequency with which fathers engage in home math activities was related to their math beliefs, attitudes, and expectations, whereas maternal home math activities were related to their beliefs, attitudes, and the gender of the child. Conclusions: The findings contribute to the understanding of the home math environment.

Beamline simulations using monochromators with high d-spacing crystals.

Monochromators for synchrotron radiation beamlines typically use perfect crystals for the hard X-ray regime and gratings for soft X-rays. There is an intermediate range, typically 1-3 keV (tender X-rays), which common perfect crystals have difficulties covering and gratings have low efficiency, although some less common crystals with high d-spacing could be suitable. To evaluate the suitability of these crystals for a particular beamline, it is useful to evaluate the crystals' performance using tools such as ray-tracing. However, simulations for double-crystal monochromators are only available for the most used crystals such as Si, Ge or diamond. Here, an upgrade of the SHADOW ray-tracing code and complementary tools in the OASYS suite are presented to simulate high d-spacing crystals with arbitrary, and sometimes complex, structures such as beryl, YB66, muscovite, etc. Isotropic and anisotropic temperature factors are also considered. The YB66 crystal with 1936 atomic sites in the unit cell is simulated, and its applicability for tender X-ray monochromators is discussed in the context of new low-emittance storage rings.

Mechanistic interrogation of mutation-independent disease modulators of RDEB identifies the small leucine-rich proteoglycan PRELP as a TGF-ß antagonist and inhibitor of fibrosis.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic extracellular matrix disease caused by deficiency in type VII collagen (Col VII). The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas. Although Col VII abundance is considered the main predictor of symptom course, previous studies have revealed the existence of mutation-independent mechanisms that control disease progression. Here, to investigate and validate new molecular modifiers of wound healing and fibrosis in a natural human setting, and toward development of disease-modulating treatment of RDEB, we performed gene expression profiling of primary fibroblast from RDEB siblings with marked phenotypic variations, despite having equal COL7A1 genotype. Gene enrichment analysis suggested that severe RDEB was associated with enhanced response to TGF-ß stimulus, oxidoreductase activity, and cell contraction. Consistently, we found an increased response to TGF-ß, higher levels of basal and induced reactive oxygen species (ROS), and greater contractile ability in collagen lattices in RDEB fibroblasts (RDEBFs) from donors with severe RDEB vs mild RDEB. Treatment with antioxidants allowed a reduction of the pro-fibrotic and contractile phenotype. Importantly, our analyses revealed higher expression and deposition in skin of the relatively uncharacterized small leucine-rich extracellular proteoglycan PRELP/prolargin associated with milder RDEB manifestations. Mechanistic investigations showed that PRELP effectively attenuated fibroblasts' response to TGF-ß1 stimulus and cell contractile capacity. Moreover, PRELP overexpression in RDEBFs enhanced RDEB keratinocyte attachment to fibroblast-derived extracellular matrix in the absence of Col VII. Our results highlight the clinical relevance of pro-oxidant status and hyper-responsiveness to TGF-ß in RDEB severity and progression. Of note, our study also reveals PRELP as a novel and natural TGF-ß antagonist with a likely dermo-epidermal pro-adhesive capacity.

Calcitonin gene-related peptide in migraine: from pathophysiology to treatment.

INTRODUCTION: It has been observed in recent years that levels of such molecules as calcitonin gene-related peptide (CGRP) and, to a lesser extent, the pituitary adenylate cyclase-activating peptide are elevated during migraine attacks and in chronic migraine, both in the cerebrospinal fluid and in the serum. Pharmacological reduction of these proteins is clinically significant, with an improvement in patients' migraines. It therefore seems logical that one of the main lines of migraine research should be based on the role of CGRP in the pathophysiology of this entity. DEVELOPMENT: The Spanish Society of Neurology's Headache Study Group decided to draft this document in order to address the evidence on such important issues as the role of CGRP in the pathophysiology of migraine and the mechanism of action of monoclonal antibodies and gepants; and to critically analyse the results of different studies and the profile of patients eligible for treatment with monoclonal antibodies, and the impact in terms of pharmacoeconomics. CONCLUSIONS: The clinical development of gepants, which are CGRP antagonists, for the acute treatment of migraine attacks, and CGRP ligand and receptor monoclonal antibodies offer promising results for these patients.

Neuroleptic malignant syndrome in a postoperative patient: A case report.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

Ocular and systemic toxicity of high-dose intravitreal topotecan in rabbits: Implications for retinoblastoma treatment.

Although many more eyes of children with retinoblastoma are salvaged now compared to just 10 years ago, the control of vitreous seeding remains a challenge. The introduction of intravitreal injection of melphalan has enabled more eyes to be salvaged safely but with definite retinal toxicity. Intensive treatment with high-dose intravitreal topotecan may be a strategy to control tumor burden because of its cell cycle-dependent cytotoxicity and the proven safety in humans. Therefore, we evaluated the ocular and systemic safety of repeated high-dose intravitreal injections of topotecan in rabbits. Systemic and ocular toxicity was assessed in non-tumor-bearing rabbits after four weekly injections of three doses of topotecan (10 µg, 25 µg, and 50 µg) or vehicle alone. Animals were evaluated weekly for general and ophthalmic clinical status. One week after the last injection, vitreous and plasma samples were collected for drug quantification and the enucleated eyes were subjected to histological assessment. Weight, hair loss, or changes in hematologic values were absent during the study period across all animal groups. Eyes injected with all topotecan doses or vehicle showed no signs of anterior segment inflammation, clinical or histologic evidence of damage to the retina, and ERG parameters remained unaltered throughout the study. Vitreous and plasma topotecan lactone concentrations were undetectable. Four weekly intravitreal injections of topotecan up to 50 µg in the animal model or a 100 µg human equivalent dose were not toxic for the rabbit eye. High doses of topotecan may show promising translation to the clinic for the management of difficult-to-treat retinoblastoma vitreous seeds.

SATB2-associated syndrome: characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients.

BACKGROUND: Individuals with pathogenic variants in SATB2 display intellectual disability, speech and behavioral disorders, dental abnormalities and often features of Pierre Robin sequence. SATB2 encodes a transcription factor thought to play a role in bone remodeling. The primary aim of our study was to systematically review the skeletal manifestations of SATB2-associated syndrome. For this purpose, we performed a non-interventional, multicenter cohort study, from 2017 to 2018. We included 19 patients, 9 females and 10 males ranging in age from 2 to 19 years-old. The following data were collected prospectively for each patient: clinical data, bone markers and calcium and phosphate metabolism parameters, skeletal X-rays and bone mineral density. RESULTS: Digitiform impressions were present in 8/14 patients (57%). Vertebral compression fractures affected 6/17 patients (35%). Skeletal demineralization (16/17, 94%) and cortical thinning of vertebrae (15/17) were the most frequent radiological features at the spine. Long bones were generally demineralized (18/19). The distal phalanges were short, thick and abnormally shaped. C-telopeptide (CTX) and Alkaline phosphatase levels were in the upper normal values and osteocalcin and serum procollagen type 1 amino-terminal propeptide (P1NP) were both increased. Vitamin D insufficiency was frequent (66.7%). CONCLUSION: We conclude that SATB2 pathogenic variants are responsible for skeletal demineralization and osteoporosis. We found increased levels of bone formation markers, supporting the key role of SATB2 in osteoblast differentiation. These results support the need for bone evaluation in children and adult patients with SATB2-associated syndrome (SAS).

Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience.

OBJECTIVE: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS: Thirty TAREs were performed in 23 patients (mean age, 61.61 ±â€¯9.13 years; 56.5% male). At three months, the objective response rate (ORR) was 16.7% and the disease control rate (DCR) 53.3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P = 0.047), previous bevacizumab treatment (P = 0.008), pre-TARE haemoglobin (P = 0.008), NLR (P = 0.040), pre-TARE albumin (P = 0.012), pre-TARE ALT (P = 0.023) and tumour-absorbed dose > 115 Gy (P = 0.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P = 0.019), KRAS mutation (HR: 5.15; P = 0.024), pre-TARE haemoglobin (HR: 0.50; p = 0.009), pre-TARE NLR (HR: 1.65; P = 0.005) and PLR (HR: 1.01; P = 0.042). CONCLUSION: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.

Guidelines of the French Society of Otorhinolaryngology-Head and Neck Surgery (SFORL) and the French Society of Audiology (SFA) for Speech-in-Noise Testing in Adults.

OBJECTIVES: This document presents the fundamentals of speech audiometry in noise, general requirements for implementation and criteria for choice among the tests available in French according to the health-professional's needs. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors, audiologists and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: Eight tests of speech audiometry in noise can be used in France. CONCLUSION: To be complete, evaluation of hearing status requires testing understanding of speech in noise. The examination must begin with a minimum of two measurements familiarizing the subject with the test procedure. For initial diagnosis, adaptive procedures establishing the 50% speech reception threshold (SRT50) in noise are to be preferred in order to obtain a rapid and standardized measurement of perception of speech in noise. When the aim is to measure real-life speech comprehension, tests based on sentences, cocktail-party noise and free-field stimulation are to be preferred. Prosthetic gain is evaluated exclusively in free field. This is the only way to evaluate the contribution of binaurality and to measure perception in noise in an environment as close as possible to real life. In order to avoid acoustic interference in free field, at least five loudspeakers should be used, in particular for evaluating the effectiveness of directional microphones, CROS devices enabling sounds picked up in the damaged ear to be rerouted to the functional ear, or bimodal fitting (i.e., when hearing is enabled by two modalities: for example, hearing aid for one ear, cochlear implant for the other).

Neuroleptic malignant syndrome in a postoperative patient: a case report. / Síndrome neuroléptico maligno en paciente postoperada: a propósito de un caso.

Neuroleptic malignant syndrome is a rare medical emergency associated with the use of antipsychotics and other antidopaminergic drugs. There is no specific test, and diagnosis is based on high clinical suspicion and good differential diagnosis. A clinical picture consistent with hyperthermia, muscle rigidity, altered level of consciousness, together with signs of rhabdomyolysis in analytical studies and a history of taking neuroleptic drugs are the key elements in the detection of this entity. Due to its low incidence and potential mortality, it is essential to publish case reports of neuroleptic malignant syndrome in order to raise awareness of this entity and facilitate diagnostic suspicion when encountering a patient with compatible symptoms. The following is the case of a 79 year old patient with chronic alcohol consumption as the only history of interest, who was given a single dose of haloperidol after an episode of delirium in the postoperative period of conventional trauma surgery. She subsequently developed a picture of progressive deterioration of the level of consciousness, diaphoresis, generalized muscle rigidity, hyperthermia, together with severe metabolic acidosis, hyperlacticaemia, rhabdomyolysis, hypertransaminasemia and hypocalcemia. After ruling out other entities compatible with the clinical picture, neuroleptic malignant syndrome was given as the main diagnostic hypothesis. Diagnosis was confirmed after clinical and analytical improvement following treatment with dantrolene. The patient was discharged from hospital with no sequelae a few days after onset of the condition.

Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience. / Biomarcadores asociados con la supervivencia y la respuesta terapéutica a la radioembolización con esferas cargadas de itrio-90 en las metástasis hepáticas del carcinoma colorrectal: nuestra experiencia.

OBJETIVE: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS: Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). CONCLUSION: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.

1st Post-European Headache Federation Meeting: a review of the latest developments presented at the 2020 European Headache Federation Congress. / I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.

INTRODUCTION: After the European Headache Federation (EHF) Congress, renowned Spanish neurologists specialised in migraine presented the most significant latest developments in research in this field at the Post-EHF Meeting. DEVELOPMENT: The main data presented concerning the treatment of chronic and episodic migraine were addressed, with attention paid more specifically to those related to preventive treatments and real-life experience in the management of the disease. An important review was carried out of the new therapeutic targets and the possibilities they offer in terms of understanding the pathophysiology of migraine and its treatment. An update was also presented of the latest developments in the treatment of migraine with fremanezumab, a monoclonal antibody recently authorised by the European Medicines Agency. Participants were also given an update on the latest developments in basic research on the pathology, as well as an overview of the symptoms of migraine and COVID-19. Finally, the repercussions of migraine in terms of its burden on the care and economic resources of the health system were addressed, along with its impact on society. CONCLUSIONS: The meeting summarised the content presented at the 14th EHF Congress, which took place in late June/early July 2020.

TITLE: I Reunión Post-European Headache Federation: revisión de las novedades presentadas en el Congreso de la European Headache Federation de 2020.Introducción. Tras la celebración del congreso de la European Headache Federation (EHF), reconocidos neurólogos españoles expertos en el tratamiento de la migraña expusieron en la Reunión Post-EHF las principales novedades presentadas en el congreso y relacionadas con ese ámbito. Desarrollo. Se abordan los principales datos presentados relacionados con el tratamiento de la migraña crónica y episódica; concretamente, los relacionados con los tratamientos preventivos y la experiencia en vida real en el manejo de la enfermedad. Se hizo una importante revisión de las nuevas dianas terapéuticas y las posibilidades que ofrecen en cuanto al conocimiento de la fisiopatología de la migraña y su tratamiento. Asimismo, se hizo una actualización de las novedades presentadas en el tratamiento de la migraña con fremanezumab, anticuerpo monoclonal recientemente autorizado por la Agencia Europea de Medicamentos. Se hizo una actualización de las novedades en investigación básica en la patología, así como una relación de los síntomas de migraña y COVID-19. Finalmente, se abordaron las implicaciones de la migraña en la carga sanitaria asistencial y económica, y su impacto en la sociedad. Conclusiones. En la reunión se hizo un resumen del contenido presentado en el 14 Congreso de la EHF, que tuvo lugar a finales de junio y principios de julio de 2020.