Sex Differences in Amyotrophic Lateral Sclerosis Survival and Progression: A Multidimensional Analysis.

OBJECTIVE: To investigate sex-related differences in amyotrophic lateral sclerosis (ALS) prognosis and their contributing factors. METHODS: Our primary cohort was the Piemonte and Aosta Register for ALS (PARALS); the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) and the Answer ALS databases were used for validation. Survival analyses were conducted accounting for age and onset site. The roles of forced vital capacity and weight decline were explored through a causal mediation analysis. Survival and disease progression rates were also evaluated after propensity score matching. RESULTS: The PARALS cohort included 1,890 individuals (44.8% women). Men showed shorter survival when stratified by onset site (spinal onset HR 1.20, 95% CI 1.00-1.44, p = 0.0439; bulbar onset HR 1.36, 95% CI 1.09-1.70, p = 0.006917), although women had a steeper functional decline (+0.10 ALSFRS-R points/month, 95% CI 0.07-0.15, p < 0.00001) regardless of onset site. Instead, men showed worse respiratory decline (-4.2 forced vital capacity%/month, 95% CI -6.3 to -2.2, p < 0.0001) and faster weight loss (-0.15 kg/month, 95% CI -0.25 to -0.05, p = 0.0030). Causal mediation analysis showed that respiratory function and weight loss were pivotal in sex-related survival differences. Analysis of patients from PRO-ACT (n = 1,394, 40.9% women) and Answer ALS (n = 849, 37.2% women) confirmed these trends. INTERPRETATION: The shorter survival in men is linked to worse respiratory function and weight loss rather than a faster disease progression. These findings emphasize the importance of considering sex-specific factors in understanding ALS pathophysiology and designing tailored therapeutic strategies. ANN NEUROL 2024;96:159-169.

Giving Breath to Motor Neurons: Noninvasive Mechanical Ventilation Slows Disease Progression in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Noninvasive mechanical ventilation (NIMV) improves amyotrophic lateral sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Here, we test whether NIMV use changed the rate of functional decline among ALS patients. METHODS: In this retrospective observational study, we included 448 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation adjusting for covariates. Functional decline was based on the nonrespiratory items of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). RESULTS: NIMV initiation resulted in a slower functional decline (mean improvement = 0.16 points per month, 95% confidence interval = 0.12-0.19, p < 0.001), with consistent effects observed across various demographic factors, including sex, age at diagnosis, and disease duration before NIMV initiation. This finding was replicated using the PRO-ACT (Pooled Resource Open-Access ALS Clinical Trials) dataset. The favorable impact of NIMV on ALSFRS-R progression was evident independently of disease stages. Notably, NIMV benefits were not dose-dependent but were particularly prominent for nighttime respiratory support. INTERPRETATION: NIMV significantly influences the rate of motor progression in ALS, and this effect is not determined by the nonlinearity of ALSFRS-R trajectory. The functional decline slowed following NIMV initiation, independently of the site of disease onset or disease severity at the time of NIMV initiation. Our findings underscore the importance of timely NIMV initiation for all ALS patients and highlight the need to consider NIMV-induced slowing of disease progression when evaluating clinical trial outcomes. ANN NEUROL 2024;95:817-822.

Plasma CHI3L1 in Amyotrophic Lateral Sclerosis: A Potential Differential Diagnostic Biomarker.

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help with defining patients' prognoses and stratifications. Besides neurofilaments, chitinases are a promising family of possible biomarkers which correlate with neuroinflammatory status. We evaluated the plasmatic levels of CHI3L1 in MNDs, MND mimics, and healthy controls (HCs). (2) Methods: We used a sandwich ELISA to quantify the CHI3L1 in plasma samples from 44 MND patients, 7 hereditary spastic paraplegia (HSP) patients, 9 MND mimics, and 19 HCs. We also collected a ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, and neuropsychological evaluation. (3) Results: The plasma levels of the CHI3L1 were different among groups (p = 0.005). Particularly, the MND mimics showed higher CHI3L1 levels compared with the MND patients and HCs. The CHI3L1 levels did not differ among PMA, PLS, and ALS, and we did not find a correlation among the CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, the red blood cell count and haemoglobin was correlated with the CHI3L1 levels (respectively, p < 0.001, r = 0.63; p = 0.022, and r = 0.52). (4) Conclusions: The CHI3L1 plasma levels were increased in the MND mimics cohort compared with MNDs group. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that the CHI3L1 plasma levels did not allow for differentiation between ALS and HCs, nor were they correlated with neuropsychological impairment.

Políticas públicas sobre violencia feminicida y feminicidio en México: una mirada desde las unidades de análisis y contexto / Políticas públicas sobre violência feminicida e feminicídio no México: um olhar das unidades de análise e contexto / Public policies on feminicide violence and femicide in Mexico: a look at the analysis and context units

El feminicidio es el asesinato de una mujer ­ o niña ­ por el hecho de ser mujer, es decir por razones de género. El término expresa la violencia extrema que se manifiesta en este acto, muchas veces perpetrado con particular crueldad, precedido de maltratos, secuestro, tortura sexual y seguido de la exposición del cadáver en el espacio público. Este texto tiene como objetivo reflexionar respecto al funcionamiento de las Unidades de Análisis y Contexto para la investigación de feminicidios, ­ creadas en el marco de las Declaratorias de Alerta de Violencia de Género en México (art. 22, LGAMVLV) ­, para observar las características jurídico-normativas, técnicas y de recursos que tienen y deberían tener de acuerdo con las recomendaciones internacionales. Sostenemos que las unidades de inteligencia y de análisis de contextos son una herramienta para la investigación criminal, que pueden funcionar para comprener el feminicidio y las violencias interseccionales en el país. A través de un análisis descriptivo y documental, privilegiamos los informes oficiales de las Unidades de Análisis y Contexto sobre violencia contra las mujeres, analizamos los principales obstáculos para la implementación de dichas unidades, y desde la perspectiva de género y pertinencia cultural, la forma y estrategias en cómo se capta la información para distinguir entre homicidio y feminicidio, y mujeres indígenas y/o afromexicanas, en un contexto de violencias estructurales y del crimen organizado

Feminicídio é o assassinato de uma mulher ­ ou menina ­ pelo fato de ser mulher, ou seja, por razões de gênero. O termo expressa a extrema violência que se manifesta neste ato, muitas vezes perpetrado com particular crueldade, precedido de maus tratos, sequestro, tortura sexual e seguido da exposição do cadáver em espaço público. O objetivo deste texto é refletir sobre o funcionamento das unidades de análise e contexto, criadas no contexto das Declarações de Alerta de Gênero no México, para observar as características jurídico-normativas, técnicas e de recursos que elas têm ou deveriam ter segundo as recomendações internacionais. Sustentamos que as unidades de inteligência e análise de contexto são uma ferramenta de investigação criminal, que pode servir para compreender o feminicídio e a violência interseccional no país. Através de uma análise descritiva e documental, privilegiamos os relatórios oficiais das unidades de análise e contexto sobre a violência contra a mulher, analisamos os principais entraves à implementação das referidas unidades e, na perspectiva da relevância cultural e de gênero, a forma e as estratégias em como as informações são coletadas para distinguir entre homicídio e feminicídio e mulheres indígenas e/ou afro-mexicanas, em um contexto de violência estrutural e crime organizado

Femicide is the murder of a woman ­ or girl ­ due to the fact of being a woman, that is, for reasons of gender. The term expresses the extreme violence that is manifested in this act, often perpetrated with particular cruelty, preceded by mistreatment, kidnapping, sexual torture and followed by the exposition of the corpse in public space. Objective: This text aims to reflect on the functioning of the Analysis and Context Units that have been created in Mexico, to observe the legal-regulatory, technical and resource characteristics that they have and should have in accordance with international recommendations. We sustain that the intelligence and context analysis units are a tool for criminal investigation, which can work to understand intersectional violence in Mexico. Through a descriptive and documentary analysis, we privilege the official reports of the Analysis and Context Units on violence against women, we analyze, based on the main obstacles to the implementation of said units, from the perspective of gender and relevance culture, as well as the way and strategies in how information is collected to distinguish between homicide and femicide, and to identify indigenous and/or Afro-Mexican women, and in a context of other structural violence and organized crime

Correction to: Efficacy of initial temozolomide for high­risk low grade gliomas in a phase II AINO (Italian Association for Neuro­Oncology) study: a post­hoc analysis within molecular subgroups of WHO 2016.

The third and fourth authors' affiliation was incorrectly specified in the original publication. It is correctly shown here.

Efficacy of initial temozolomide for high-risk low grade gliomas in a phase II AINO (Italian Association for Neuro-Oncology) study: a post-hoc analysis within molecular subgroups of WHO 2016.

INTRODUCTION: The optimal management of high risk WHO grade II gliomas after surgery is debated including the role of initial temozolomide to delay radiotherapy and risk of cognitive defects. METHODS: A post-hoc analysis of a phase II multicenter study on high risk WHO grade II gliomas, receiving initial temozolomide alone, has re-evaluated the long-term results within the molecular subgroups of WHO 2016. The primary endpoint of the study was response according to RANO, being seizure response, PFS and OS secondary endpoints. RESULTS: Response rate among oligodendrogliomas IDH-mutant and 1p/19q codeleted (76%) was significantly higher than that among diffuse astrocytomas either mutant (55%) or wild-type (36%). A reduction of seizure frequency > 50% was observed in 87% of patients and a seizure freedom in 72%. The probability of seizure reduction > 50% was significantly associated with the presence of an IDH mutation. Median PFS, PFS at 5 and 10 years, median OS and OS at 5 and 10 years were significantly longer in oligodendrogliomas IDH-mutant and 1p/19q codeleted. Sixty-seven percent of patients with oligodendroglioma IDH mutant and 1p/19q codeleted did not recur with a median follow up of 9.3 years, while 59% did not receive radiotherapy at recurrence with a median follow up of 8.2 years. CONCLUSIONS: The beneficial effects of initial temozolomide prevail in oligodendrogliomas IDH-mutant and 1p/19q codeleted: thus, these tumors, when incompletely resected or progressive after surgery alone, or with intractable seizures, should receive temozolomide as initial treatment with salvage radiotherapy and/o reoperation and/or second-line chemotherapy at recurrence.