Amantadine and/or transcranial magnetic stimulation for fatigue associated with multiple sclerosis (FETEM): study protocol for a phase 3 randomised, double-blind, cross-over, controlled clinical trial.

INTRODUCTION: Fatigue is one of the most disabling symptoms of multiple sclerosis (MS), and effective treatments are lacking. Amantadine is one of the most used treatments, although its efficacy is under debate. Transcranial magnetic stimulation (TMS) is a promising intervention that has shown positive effects in some preliminary investigations. We aim to investigate the effect of 6 weeks of amantadine and/or TMS in fatigue due to MS. METHODS AND ANALYSIS: The study is a national, multicentre, phase 3, randomised, double-blind, cross-over, placebo-controlled and sham-controlled clinical trial. Adult patients with relapsing-remitting MS, Expanded Disability Status Scale score of 1.5-4.5 and Fatigue Severity Score>4 are eligible for the trial. Participants will be randomised to one of the sequences of the study. Each sequence consists of four periods of 6 weeks of treatment and three washout periods of 12-18 weeks. All patients will receive all the combinations of therapies. The primary outcome is the Modified Fatigue Impact Scale. The secondary outcomes are the Symbol Digit Modalities Test (cognition), Beck Depression Inventory-II (depressive symptoms) and Short-Survey 12 (quality of life). Safety and cost-effectiveness will also be evaluated. An exploratory substudy including MRI and blood biomarkers will be conducted. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committee of the Hospital Clinico San Carlos and the Spanish Agency of Medications and Medical Devices. All study findings will be published in scientific peer-reviewed journals and presented at relevant scientific conferences. TRIAL REGISTRATION NUMBER: EudraCT 2021-004868-95; NCT05809414.

Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

Burden of lupus activity on health care resources utilization in Buenos Aires, Argentina.

OBJECTIVE: The aim is to analyze health care resource utilization (HCRU) of patients with lupus (SLE) from a health management organization (HMO) in Buenos Aires, Argentina, compared with matched controls and comparing periods of flare, low disease activity, and remission. METHODS: This is a retrospective observational study including all SLE incident cases (ACR 1997/SLICC 2012 criteria) between 2000 and 2020 and 5 matched controls. Clinical data and HCRU (medical and nonmedical consultations, lab and imaging tests performed, emergency room visits, hospitalizations, and drugs prescribed) were obtained from administrative databases and electronic medical records. For each patient with SLE, an activity state was determined in every month of follow-up: flare (BILAG A or 2 BILAG B); low disease activity (LLDAS); remission (DORIS definition); or intermediate activity (not fulfilling any of previous). Incidence rates for each HCRU item and incidence rate ratios between SLE and control patients were and between remission and flare periods were calculated. Multivariate negative binomial logistic regression analyses were performed for identification of variables associated with major resource use. RESULTS: A total of 62 SLE and 310 control patients were included, 88.7% were women, the median age at diagnosis was 46 years, and were followed for more than 8 years. Patients with SLE contributed with 537.2 patient-years (CI 95% 461.1-613.3) and controls with 2761.9 patient-years (CI 95% 2600.9-2922.8). HCRU in patients with SLE was significantly higher than in controls in all items, even in remission periods. Patients with SLE remained 74.4% of the time in remission, 12.1% in LLDAS, 12.2% in intermediate activity, and 1.3% in flare (there were 64 flares in 36 patients). HCRU was significantly higher during flare periods compared with remission periods. Number of flares was independently associated with emergency department consultations, lab tests and X-ray performed, number of drugs prescribed, and hospitalizations. CONCLUSION: Significantly more HCRU was observed in patients with SLE in flare compared to remission periods.

Neuroimaging and serum biomarkers of neurodegeneration and neuroplasticity in Parkinson's disease patients treated by intermittent theta-burst stimulation over the bilateral primary motor area: a randomized, double-blind, sham-controlled, crossover trial study.

Background and objectives: Intermittent theta-burst stimulation (iTBS) is a patterned form of excitatory transcranial magnetic stimulation that has yielded encouraging results as an adjunctive therapeutic option to alleviate the emergence of clinical deficits in Parkinson's disease (PD) patients. Although it has been demonstrated that iTBS influences dopamine-dependent corticostriatal plasticity, little research has examined the neurobiological mechanisms underlying iTBS-induced clinical enhancement. Here, our primary goal is to verify whether iTBS bilaterally delivered over the primary motor cortex (M1) is effective as an add-on treatment at reducing scores for both motor functional impairment and nonmotor symptoms in PD. We hypothesize that these clinical improvements following bilateral M1-iTBS could be driven by endogenous dopamine release, which may rebalance cortical excitability and restore compensatory striatal volume changes, resulting in increased striato-cortico-cerebellar functional connectivity and positively impacting neuroglia and neuroplasticity. Methods: A total of 24 PD patients will be assessed in a randomized, double-blind, sham-controlled crossover study involving the application of iTBS over the bilateral M1 (M1 iTBS). Patients on medication will be randomly assigned to receive real iTBS or control (sham) stimulation and will undergo 5 consecutive sessions (5 days) of iTBS over the bilateral M1 separated by a 3-month washout period. Motor evaluation will be performed at different follow-up visits along with a comprehensive neurocognitive assessment; evaluation of M1 excitability; combined structural magnetic resonance imaging (MRI), resting-state electroencephalography and functional MRI; and serum biomarker quantification of neuroaxonal damage, astrocytic reactivity, and neural plasticity prior to and after iTBS. Discussion: The findings of this study will help to clarify the efficiency of M1 iTBS for the treatment of PD and further provide specific neurobiological insights into improvements in motor and nonmotor symptoms in these patients. This novel project aims to yield more detailed structural and functional brain evaluations than previous studies while using a noninvasive approach, with the potential to identify prognostic neuroprotective biomarkers and elucidate the structural and functional mechanisms of M1 iTBS-induced plasticity in the cortico-basal ganglia circuitry. Our approach may significantly optimize neuromodulation paradigms to ensure state-of-the-art and scalable rehabilitative treatment to alleviate motor and nonmotor symptoms of PD.

Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

BACKGROUND: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. METHODS: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. FINDINGS: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. INTERPRETATION: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. FUNDING: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Rheumatoid arthritis monotherapy in the Jak inhibitors Era. Current prevalence and associated factors in a multicenter study.

BACKGROUND: Combined therapy constitutes the standard of care in RA. Jak inhibitors (Jaki) have shown efficacy in monotherapy, a modality used in cases where it is not possible to use Disease-Modifying Anti Rheumatic Drugs (csDMARDs). OBJECTIVES: To estimate the prevalence (total and by drug), reason for using and the increase over the time of bDMARDs or tsDMARDs as monotherapy after the availability of the Jaki. To analyze the differential characteristics between patients with monotherapy vs combined therapy. METHODS: Cross-sectional multicenter study. Consecutive patients with a diagnosis of RA (ACR/EULAR 2010) under treatment with bDMARDs or tsDMARDs started from 2013 were included. Socio-demographic, clinic, and therapeutic data were collected. RESULTS: A total of 505 RA patients were included. Since 2013, the prevalence of monotherapy usage was (any) 49%. The drugs used as monotherapy were Jaki in 41% and TNF-blockers in 30%. The leading causes of monotherapy use were intolerance/adverse events (62%), medical decision or lack of adherence (37.7%). The highest socioeconomic level and a better functional status at diagnosis were predictors of monotherapy use. The use of the second line of treatments and less polypharmacy were independent factors associated with this therapeutic modality. CONCLUSIONS: The current prevalence of monotherapy in RA was 49%, the Jaki were the most used drug in this modality. Monotherapy increases from year to year. There are differential characteristics in patients using monotherapy.

Neuropsychological and Neuropsychiatric Features of Chronic Migraine Patients during the Interictal Phase.

This study aimed to examine the presence of neuropsychological deficits and their relationships with clinical, pharmacological, and neuropsychiatric characteristics in chronic migraine (CM) patients assessed during a headache-free period. We enrolled 39 CM patients (mean age: 45.4 years; male/female ratio: 3/36) and 20 age-, sex-, and education-matched healthy controls (HCs, mean age: 45.5 years; male/female ratio: 2/18) in a case-control study. All CM patients underwent a full and extensive clinical, neuropsychiatric, and neuropsychological evaluation to evaluate cognitive domains, including sustained attention (SA), information processing speed (IPS), visuospatial episodic memory, working memory (WM), and verbal fluency (VF), as well as depressive and anxiety symptoms. CM patients exhibited higher scores than HCs for all clinical and neuropsychiatric measures, but no differences were found in personality characteristics. Although more than half of the CM patients (54%) showed mild-to-severe neuropsychological impairment (NI), with the most frequent impairments occurring in short- and long-term verbal episodic memory and inhibitory control (in approximately 90% of these patients), almost half of the patients (46%) showed no NI. Moreover, the severity of NI was positively associated with the number of pharmacological treatments received. Remarkably, disease-related symptom severity and headache-related disability explained global neuropsychological performance in CM patients. The presence of cognitive and neuropsychiatric dysfunction during the interictal phase occurred in more than half of CM patients, increasing migraine-related disability and possibly exerting a negative impact on health-related quality of life and treatment adherence.

Prognostic factors associated with advanced chronic kidney disease in a cohort of patients with ANCA vasculitis and renal involvement.

OBJECTIVE: The aim of this study was to evaluate prognostic factors associated with advanced chronic kidney disease (ACKD) in a cohort of patients with ANCA-associated vasculitis and renal involvement. METHODS: Observational retrospective study. We included patients with biopsy-proven ANCA glomerulonephritis (GN) diagnosed between 2001 and 2016, with at least 1-year follow-up. Data were recorded at diagnosis, end of induction, after 12 months of treatment, and at the end of follow-up. We analysed clinical-analytical data and renal histopathology, as well as treatments, dialysis requirement, relapses and death. Univariate analysis was performed to identify factors associated with long-term ACKD (eGFR < 30 ml/min). Multivariate analysis using an alternative outcome (eGFR at the end of follow-up) was performed. Diagnostic accuracy for ACKD of each predictor variable was compared using AUC of ROC curves. RESULTS: Sixty patients were included: 17 GPA, 14 MPA, 5 EGPA, and 24 RLV. Forty-six patients were women (76.7%). Mean age at diagnosis was 67.8 years (SD 13.1), and median follow-up time was 4.2 years (IQR 2.2-6.8). At the end of follow-up, 12 patients (20.0%) had an eGFR < 30 ml/min. Univariate analysis showed a statistically significant association of ACKD with sclerotic class biopsy (OR 7.17, 95% CI 1.34-38.31), 12-month proteinuria (OR 5.16, 95% CI 1.16-22.87), and creatinine at diagnosis (OR 1.24, 95% CI 1.02-1.52), end of induction (OR 15.40, 95% CI 2.41-98.28), and after 12 months (OR 19.25, 95% CI 2.75-134.92). In the multivariate analysis, eGFR at baseline (< 0.001), after 6 months (< 0.001) and 12 months of treatment (< 0.001), remained statistically associated with eGFR at the end of follow-up. The best diagnostic accuracy in ROC curves was shown by serum creatinine at the end of induction treatment (AUC 0.93) and after 12 months (AUC 0.94). CONCLUSION: In this cohort of patients with ANCA GN, creatinine and eGFR at baseline and after 6 and 12 months of treatment were the best predictors of ACKD at the end of follow-up.

A new set of estimated cardiorespiratory fitness equations are associated with cognitive performance in older adults.

This study aimed to develop new equations to estimate cardiorespiratory fitness specifically for older adults and, secondly, to analyze the associations of cardiorespiratory fitness, both objectively measured and estimated using new equations, with cognitive performance. Ninety-two older adults (41 females, 65-75 years) from baseline data of a randomized controlled trial were analyzed ("ClinicalTrials.gov" Identifier: NCT03923712). Participants completed 4 measurement sessions including (i) physiological and health indicators in a laboratory setting, (ii) field-based fitness tests, (iii) sociodemographic and physical activity questionnaires, and (iv) a battery of neuropsychological tests to evaluate cognitive performance. The main findings were as follows: (i) a set of new equations with good predictive value for estimated cardiorespiratory fitness were developed (74-87%), using different scenarios of complexity and/or equipment requirements, and (ii) higher estimated cardiorespiratory fitness, even using its simplest equation (eCRF = - 1261.99 + 1.97 × 6 min walking test (m) + 1.12 × bioimpedance basal metabolic rate (kcal/day) + 5.25 × basal heart rate (bpm)), was associated with better cognitive performance evaluated by several neuropsychological tests (i.e., language, cognitive flexibility, fluency, attention, and working memory), similar to using objectively measured cardiorespiratory fitness. In summary, a new set of estimated cardiorespiratory fitness equations have been developed with predictive values ranging from 74 to 87% that could be used based on necessity, availability of equipment, resources, or measurement context. Moreover, similar to objectively measured cardiorespiratory fitness, this measure of estimated cardiorespiratory fitness was positively associated with performance on language, fluency, cognitive flexibility, attention, and working memory, independently of sex, age, and education level.

Incidence and Prevalence of Polymyalgia Rheumatica and Giant Cell Arteritis in a Healthcare Management Organization in Buenos Aires, Argentina.

OBJECTIVE: To estimate incidence and prevalence of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in a university hospital-based health management organization (Hospital Italiano Medical Care Program) in Argentina. METHODS: Overall and sex-specific incidence rates (IRs) and prevalence were calculated (age ≥ 50 yrs). Incidence study followed members with continuous affiliation ≥ 1 year from January 2000 to December 2015. Diagnosis as per the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology (ACR) criteria for PMR or the ACR 1990 criteria for GCA. Prevalence was calculated on January 1, 2015. RESULTS: There were 176,558 persons who contributed a total of 1,046,620 person-years (PY). Of these, 825 developed PMR, with an IR (per 100,000 PY) of 78.8 (95% CI 73.4-84.2) overall, 90.1 (95% CI 82.9-97.2) for women, and 58.9 (95% CI 51.1-66.6) for men. Ninety persons developed GCA; the IR was 8.6 (95% CI 6.8-10.4) overall, 11.1 (95% CI 8.5-10.6) for women, and 4.2 (2.2-6.3) for men. There were 205 prevalent PMR cases and 23 prevalent GCA cases identified from a population of 80,335. Prevalence of PMR was 255 per 100,000 (95% CI 220-290) overall, 280 (95% CI 234-325) for women, and 209 (95% CI 150-262) for men; and the prevalence of GCA was 28.6 per 100,000 (95% CI 16.9-40.3) overall, 36.4 (95% CI 20.1-52.8) for women, and 14.2 (95% CI 0.3-28.1) for men. CONCLUSION: This is the first study of incidence and prevalence of PMR and GCA in Argentina. There were similarities and differences with cohorts from other parts of the world, but population-based epidemiologic studies in Latin America are needed.

Relación entre fibromialgia y sarcopenia: el papel del abordaje nutricional / Fibromyalgia and sarcopenia relation: the role of nutritional approach

Introducción: la fibromialgia (FM) es un síndrome caracterizado por la presencia de dolor musculoesquelético crónico y generalizado, de origen no articular, que puede llegar a ser invalidante y afectar la esfera biológica, psicológica y social del paciente. Estado del arte: no se han publicado recomendaciones nutricionales específicas para las personas con FM y también existe un vago conocimiento acerca de los parámetros relacionados con la evaluación de la composición corporal (masa musculoesquelética, masa grasa, agua corporal, etc.) y la alteración en la fuerza muscular (p. ej., dinapenia, por dinamometría de mano, flexión de la rodilla, entre otras), así como la evaluación en términos de sarcopenia. Discusión: pocos estudios publicados hasta el momento describen en profundidad la composición corporal de las personas con FM. La mayoría se centran casi exclusivamente en la descripción del peso y el índice de masa corporal (IMC), por lo que existe poco conocimiento acerca de otros parámetros de relevancia, como por ejemplo aquellos relacionados con masa y fuerza muscular o masa grasa. La alimentación se menciona en varias publicaciones, pero no existen guías o pautas específicas de recomendaciones nutricionales para esta población. Algunos pacientes adoptan diversas dietas, estrategias o planes alimentarios sin ningún tipo de orientación de los profesionales de la salud, e incluso a veces, siguiendo fuentes de información no fiables, poniendo en riesgo su salud. Las publicaciones científicas no evalúan la asociación o el impacto del estado nutricional y la inadecuada alimentación en la calidad de vida. Conclusiones: en las personas con FM, conocer el estado nutricional, más allá del peso, determinando la composición corporal y la prevalencia de dinapenia o sarcopenia o ambas permitiría realizar un abordaje nutricional más adecuado. Este conocimiento podría ser coadyuvante en la terapéutica, logrando una mejoría en su desempeño físico y una mejor calidad de vida. (AU)

Introduction: fibromyalgia (FM) is a syndrome charcaterized by the presence of chronic, and generalized musculoskeletal pain, not articular in origin, which can become disabling and affect the biological, psychological, and social sphere of the patient. State of the art: no specific nutritional recommendations have been published for people with FM and there is also a vague knowledge regarding parameters related to body composition assessment (skeletal muscle mass, body fat mass, water, etc.) and loss of muscle strength (for example, dynapenia, by handgrip, knee flexion, among others), as well as assessment in terms of sarcopenia. Discussion: there are few studies published so far that completely describe the body composition in people with FM. Most of them focus almost exclusively on weight and body mass index (BMI), so there is a lack of knowledge about other descriptive parameters, such as those related to muscle mass and strength or fat mass. Diet is mentioned in several publications, but there are no specific guidelines for nutritional recommendations for this population. Some patients follow several diets, strategies or eating plans without health care professionals' guidance, and sometimes even following unreliable sources of information, putting themselves at risk. Scientific publications do not evaluate the association or impact of nutritional status and inadequate nutrition on quality of life in FM. Conclusions: in people with FM, knowledge of the nutritional status, beyond weight, determining body composition and the prevalence of dynapenia and/or sarcopenia would allow a more accurate nutritional approach. This knowledge could be helpful for the treatment, achieving an improvement in their physical performance and a better quality of life. (AU)

A Causal Analysis of the Effect of Age and Sex Differences on Brain Atrophy in the Elderly Brain.

We studied how brain volume loss in old age is affected by age, the APOE gene, sex, and the level of education completed. The quantitative characterization of brain volume loss at an old age relative to a young age requires-at least in principle-two MRI scans, one performed at a young age and one at an old age. There is, however, a way to address this problem when having only one MRI scan obtained at an old age. We computed the total brain losses of elderly subjects as a ratio between the estimated brain volume and the estimated total intracranial volume. Magnetic resonance imaging (MRI) scans of 890 healthy subjects aged 70 to 85 years were assessed. A causal analysis of factors affecting brain atrophy was performed using probabilistic Bayesian modelling and the mathematics of causal inference. We found that both age and sex were causally related to brain atrophy, with women reaching an elderly age with a 1% larger brain volume relative to their intracranial volume than men. How the brain ages and the rationale for sex differences in brain volume losses during the adult lifespan are questions that need to be addressed with causal inference and empirical data. The graphical causal modelling presented here can be instrumental in understanding a puzzling scientific area of study-the biological aging of the brain.

Inflammation- and Metastasis-Related Proteins Expression Changes in Early Stages in Tumor and Non-Tumor Adjacent Tissues of Colorectal Cancer Samples.

Chronic inflammation can induce malignant cell transformation, having an important role in all colorectal cancer (CRC) phases. Non-tumor adjacent tissue plays an important role in tumor progression, but its implication in CRC has not yet been fully elucidated. The aim was to analyze the expression of inflammatory, epithelial-mesenchymal transition (EMT), and metastasis-related proteins in both tumor and non-tumor adjacent tissues from CRC patients by western blot. Tumor tissue presented an increase in metastasis and EMT-related proteins compared to non-tumor adjacent tissue, especially in stage II. Tumor tissue stage II also presented an increase in inflammatory-related proteins compared to other stages, which was also seen in non-tumor adjacent tissue stage II. Additionally, the relapse-free survival study of Vimentin and VEGF-B expression levels in stage II patients showed that the higher the expression levels of each protein, the lower 10-year relapse-free survival. These could suggest that some metastasis-related signalling pathways may be activated in stage II in tumor tissue, accompanied by an increase in inflammation. Furthermore, non-tumor adjacent tissue presented an increase of the inflammatory status that could be the basis for future tumor progression. In conclusion, these proteins could be useful as biomarkers of diagnosis for CRC at early stages.

Sarcopenia y su relevancia en la práctica clínica / Sarcopenia and its relevance in clinical practice

La sarcopenia se define como una combinación de baja fuerza y masa muscular con alteración funcional del músculo, que afecta a poblaciones de diferentes edades por diversos motivos. La prevalencia global en adultos mayores se ha estimado en 10% (IC 95%: 8-12%) en hombres y 10% (IC 95%: 8-13%) en mujeres. Recientemente ha cobrado importancia su detección en enfermedades reumáticas, particularmente las inflamatorias. En esta revisión narrativa hemos considerado: a) recomendaciones para el diagnóstico de la sarcopenia; b) herramientas útiles para la práctica clínica y la investigación; c) su relación con las enfermedades reumáticas. Según el último Consenso Europeo de Sarcopenia la búsqueda debe comenzar cuando el paciente reporta síntomas y/o signos (debilidad, lentitud al caminar, desgaste muscular, pérdida de masa muscular, etc.). Para los adultos mayores se recomienda el cuestionario SARC-F como herramienta de tamizaje. Varias pruebas establecen los puntos de corte que deben utilizarse para diagnosticar la baja fuerza muscular, la disminución en la masa muscular y la alteración en el rendimiento físico. La relevancia de diagnosticar precozmente la sarcopenia se basa en el impacto clínico, económico y social que tiene, incluyendo la funcionalidad y calidad de vida de las personas, muy importante en aquellas con enfermedades reumatológicas.

Sarcopenia is defined as a combination of low muscle strength and mass with muscle function impairment that affects the population at different age ranges for different reasons. The global prevalence at the elderly was estimated at 10% (95% CI: 8-12%) in men and 10% (95% CI: 8-13%) in women. In recent years, the detection of sarcopenia in rheumatic diseases has become relevant. The aim of this revision was to develop a review regarding: a) recommendations for the diagnosis of sarcopenia; b) most useful tools for detection in clinical practice and research; c) relationship with some rheumatic diseases. According to the latest European Sarcopenia Consensus, in clinical practice, the search must start when the patient reports symptoms and signs (weakness, slow walking, muscle wasting, disease that leads to muscle loss, etc.). For the elderly population the SARC-F test is recommended as a screening tool. Several tests have established cut-off points to be used to diagnose low muscle strength, decrease in muscle mass or physical performance impairment. The relevance of early diagnosis of sarcopenia is based on the clinical, economic, social impact and also on functionality and quality of life in people, particularly in those with rheumatic diseases.

A bridge too far for artificial intelligence?: Automatic classification of stanzas in Spanish poetry.

The rise in artificial intelligence and natural language processing techniques has increased considerably in the last few decades. Historically, the focus has been primarily on texts expressed in prose form, leaving mostly aside figurative or poetic expressions of language due to their rich semantics and syntactic complexity. The creation and analysis of poetry have been commonly carried out by hand, with a few computer-assisted approaches. In the Spanish context, the promise of machine learning is starting to pan out in specific tasks such as metrical annotation and syllabification. However, there is a task that remains unexplored and underdeveloped: stanza classification. This classification of the inner structures of verses in which a poem is built upon is an especially relevant task for poetry studies since it complements the structural information of a poem. In this work, we analyzed different computational approaches to stanza classification in the Spanish poetic tradition. These approaches show that this task continues to be hard for computers systems, both based on classical machine learning approaches as well as statistical language models and cannot compete with traditional computational paradigms based on the knowledge of experts.

Frecuencia de infección por SARS-CoV-2 en asistentes a un congreso médico en la Ciudad Autónoma de Buenos Aires. Datos del Congreso Argentino de Reumatología 2021 / Frequency of SARS-CoV-2 infection in attendees at a medical congress in the Autonomous City of Buenos Aires. Data from the Argentine Congress of Rheumatology 2021

Introducción: en el contexto de la pandemia por SARS-CoV-2, la Sociedad Argentina de Reumatología (SAR) organizó su congreso "híbrido" (presencial y virtual), en diciembre de 2021, en concordancia con la condición epidemiológica. El objetivo principal de este trabajo fue describir la frecuencia de nuevos casos de infección luego de asistir al Congreso y la opinión de los médicos sobre los aspectos de bioseguridad del evento, y como objetivo secundario, analizar las características de los asistentes durante la pandemia por SARS-CoV-2. Materiales y métodos: estudio transversal a través de una encuesta online, autoadministrada y anónima. Se encuestaron a los concurrentes (médicos y no médicos) al Congreso (presencial o virtual). La primera encuesta fue al momento de la inscripción y la segunda luego de 14 días de culminado, solo para los médicos. Se realizó un análisis descriptivo de los resultados. Resultados: 1.322 individuos se inscribieron al Congreso; 1.039 (98,9%) eran médicos. 1.051 (79,5%) completaron la primera encuesta y 501 (48,2%) contestaron la segunda. Mientras 428 (85,4%) asistieron presencialmente, la virtualidad la eligieron aquellos con más años de ejercicio (p=0,023), con comorbilidades (p=0,03) y quienes tuvieron una internación previa por SARS-CoV-2 (p=0,05). Del total, 1.028 (97,8%) estaban vacunados. El 84,6% tuvo una opinión favorable sobre la modalidad "híbrida". Cinco (1,2%) presentaron síntomas de infección por SARS-CoV-2 y tres (0,7%) tuvieron confirmación diagnóstica. Conclusiones: cinco personas registraron la infección sintomática después del evento. Las medidas de bioseguridad tomadas fueron las aconsejadas por el Ministerio de Salud de la Nación y la opinión de los médicos sobre las mismas fueron favorables.

Introduction: in the context of the pandemic due to SARS-CoV-2, the Argentine Society of Rhematology organized its "hybrid" congress (face-to-face and virtual), on December 2021, in accordance with the epidemiological condition. The main objective of this work was to describe the frequency of new cases of infection after attending the Congress and the opinion of doctors on the biosafety aspects of the event, and as a secondary objective, to analyze the characteristics of those attending the Congress during the pandemic. by SARS-CoV-2. Materials and methods: cross-sectional study, through an online, self-administered and anonymous survey. The attendees (physician and non- physician) to the congress (face-to-face or virtual) were surveyed. The first survey was at the time of registration and the second after 14 days of finish, only for physicians. A descriptive analysis of the results was performed. Results: 1,322 subjects registered for Congress; 1,039 (98.9%) were physicians. 1,051 (79.5%) completed the first survey and 501 (48.2%) answered the second. While 428 (85.4%) attended in person, virtuality was chosen by those with more years of practice (p=0.023), with comorbidities (p=0.03) and those who had a previous hospitalization for SARS-CoV-2 (p =0.05). Of the total, 1,028 (97.8%) were vaccinated. 84.6% had a favorable opinion about the "hybrid" modality. Five (1.2%) presented symptoms of SARS-CoV-2 infection and three (0.7%) had diagnostic confirmation. Conclusions: five subjects had symptoms and three confirmed infections. The biosafety measures taken were those recommended by the Ministry of Health and the opinion of the colleagues about them was favorable.

Prediction of Chronological Age in Healthy Elderly Subjects with Machine Learning from MRI Brain Segmentation and Cortical Parcellation.

Normal aging is associated with changes in volumetric indices of brain atrophy. A quantitative understanding of age-related brain changes can shed light on successful aging. To investigate the effect of age on global and regional brain volumes and cortical thickness, 3514 magnetic resonance imaging scans were analyzed using automated brain segmentation and parcellation methods in elderly healthy individuals (69-88 years of age). The machine learning algorithm extreme gradient boosting (XGBoost) achieved a mean absolute error of 2 years in predicting the age of new subjects. Feature importance analysis showed that the brain-to-intracranial-volume ratio is the most important feature in predicting age, followed by the hippocampi volumes. The cortical thickness in temporal and parietal lobes showed a superior predictive value than frontal and occipital lobes. Insights from this approach that integrate model prediction and interpretation may help to shorten the current explanatory gap between chronological age and biological brain age.

Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.

Background: Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods: We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases-PubMed, Scopus, and Dialnet-were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results: In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions: NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.