Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006). CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Through the orbit and beyond: Current state and future perspectives in endoscopic orbital surgery on behalf of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Introduction: Orbital surgery has always been disputed among specialists, mainly neurosurgeons, otorhinolaryngologists, maxillofacial surgeons and ophthalmologists. The orbit is a borderland between intra- and extracranial compartments; Krönlein's lateral orbitotomy and the orbitozygomatic infratemporal approach are the historical milestones of modern orbital-cranial surgery. Research question: Since its first implementation, endoscopy has significantly impacted neurosurgery, changing perspectives and approaches to the skull base. Since its first application in 2009, transorbital endoscopic surgery opened the way for new surgical scenario, previously feasible only with extensive tissue dissection. Material and methods: A PRISMA based literature search was performed to select the most relevant papers on the topic. Results: Here, we provide a narrative review on the current state and future trends in endoscopic orbital surgery. Discussion and conclusion: This manuscript is a joint effort of the EANS frontiers committee in orbital tumors and the EANS skull base section.

Short-term Macrochloa tenacissima response understory Pinus halepensis Mill forest after early prescribed burns in a semi-arid landscape.

Climate change has led to altered fire patterns in the Mediterranean basin due to rising temperatures and greenhouse gas emissions, diminishing the resilience of forest ecosystems. To address this threat, forest management increasingly employs preventive measures like controlled burns, aiming to mitigate wildfire damage. However, understanding the impact of prescribed burns on vegetation remains crucial. Our study focuses on assessing the ecological effects of early-season prescribed burns on Macrochloa tenacissima communities within Pinus halepensis Mill forests on the Iberian Peninsula. These forests, with southeast-facing slopes and arid soils, heavily rely on alpha grass for post-fire recovery, acting as a shield against runoff and erosion. Yet, the presence of highly flammable resprouting species can lead to rapid combustible material accumulation. We evaluated parameters like coverage, floral diversity (α-diversity), aboveground plant biomass, photosynthetic activity, and chemical leaf properties of alpha grass, a year after a low-intensity controlled burn. Comparing burnt and unburnt areas revealed significant changes in α-diversity and ecophysiology of Macrochloa tenacissima due to early-season prescribed burns. These short-term shifts underscore the need for further exploration of underlying mechanisms. Our analysis also showed distinct shifts in alpha grass leaf chemical composition between the two plot types, potentially impacting post-fire recovery strategies. Although prescribed burning might not be optimal for reducing fire risk in resprouting species-dominated forests, it conserves native plants and enhances ecosystem diversity, providing valuable ecological benefits. In conclusion, our research deepens our understanding of early-season burning's repercussions on flammable vegetation dynamics and combustible material availability in semi-arid landscapes. It contributes to standardized management protocols, aiding effective forest service administration and wildfire risk reduction.

Multidisciplinary approach of the sequelae one month after hospital discharge in patients with severe bilateral COVID-19 pneumonia, are there differences depending on the respiratory therapy used during admission to intensive care?

OBJECTIVE: To describe the sequelae one month after hospital discharge in patients who required admission to Intensive Care for severe COVID 19 pneumonia and to analyze the differences between those who received therapy exclusively with high-flow oxygen therapy compared to those who required invasive mechanical ventilation. DESIGN: Cohort, prospective and observational study. SETTING: Post-intensive care multidisciplinary program. PATIENTS OR PARTICIPANTS: Patients who survived admission to the intensive care unit (ICU) for severe COVID 19 pneumonia from April 2020 to October 2021. INTERVENTIONS: Inclusion in the post-ICU multidisciplinary program. MAIN VARIABLES OF INTEREST: Motor, sensory, psychological/psychiatric, respiratory and nutritional sequelae after hospital admission. RESULTS: 104 patients were included. 48 patients received high-flow nasal oxygen therapy (ONAF) and 56 invasive mechanical ventilation (IMV). The main sequelae found were distal neuropathy (33.9% IMV vs 10.4% ONAF); brachial plexopathy (10.7% IMV vs 0% ONAF); decrease in grip strength: right hand 20.67kg (±8.27) in VMI vs 31.8kg (±11.59) in ONAF and left hand 19.39kg (±8.45) in VMI vs 30.26kg (±12.74) in ONAF; and limited muscle balance in the lower limbs (28.6% VMI vs 8.6% ONAF). The differences observed between both groups did not reach statistical significance in the multivariable study. CONCLUSIONS: The results obtained after the multivariate study suggest that there are no differences in the perceived physical sequelae one month after hospital discharge depending on the respiratory therapy used, whether it was high-flow nasal oxygen therapy or prolonged mechanical ventilation, although more studies are needed to be able to draw conclusions.

[Multidisciplinary approach of the sequelae one month after hospital discharge in patients with severe bilateral COVID-19 pneumonia, are there differences depending on the respiratory therapy used during admission to intensive care?] / Valoración multidisciplinar de las secuelas al mes del alta hospitalaria por neumonía grave COVID-19, ¿existen diferencias en función de la terapia respiratoria empleada durante su ingreso en Cuidados Intensivos?

Objective: To describe the sequelae one month after hospital discharge in patients who required admission to intensive care for severe COVID-19 pneumonia and to analyze the differences between those who received therapy exclusively with high-flow oxygen therapy compared to those who required invasive mechanical ventilation. Design: Cohort, prospective and observational study. Setting: Post-intensive care multidisciplinary program. Patients or participants: Patients who survived admission to the intensive care unit (ICU) for severe COVID-19 pneumonia from April 2020 to October 2021. Interventions: Inclusion in the post-ICU multidisciplinary program. Main variables of interest: Motor, sensory, psychological/psychiatric, respiratory and nutritional sequelae after hospital admission. Results: One hundred and four patients were included. 48 patients received high-flow nasal oxygen therapy (ONAF) and 56 invasive mechanical ventilation (IMV). The main sequelae found were distal neuropathy (33.9% IMV vs. 10.4% ONAF); brachial plexopathy (10.7% IMV vs. 0% ONAF); decrease in grip strength: right hand 20.67 kg (± 8.27) in VMI vs. 31.8 kg (± 11.59) in ONAF and left hand 19.39 kg (± 8.45) in VMI vs. 30.26 kg (± 12.74) in ONAF; and limited muscle balance in the lower limbs (28.6% VMI vs. 8.6% ONAF). The differences observed between both groups did not reach statistical significance in the multivariable study. Conclusions: The results obtained after the multivariate study suggest that there are no differences in the perceived physical sequelae one month after hospital discharge depending on the respiratory therapy used, whether it was high-flow nasal oxygen therapy or prolonged mechanical ventilation, although more studies are needed to be able to draw conclusions.

Post-fire management effects on hillslope-stream sediment connectivity in a Mediterranean forest ecosystem.

Forest fires intensify sediment transport and aggravate local and off-site consequences of soil erosion. This study evaluates the influence of post-fire measures on structural and functional sediment connectivity (SC) in five fire-affected Mediterranean catchments, which include 929 sub-catchments, by using the "aggregated index of connectivity" (AIC) at two temporal scenarios: I) immediately after the fire and before implementing post-fire practices ('Pre-man'), and II) two years after the fire ('Post-man'). The latter includes all the emergency stabilization practices, that are hillslope barriers, check-dams and afforestation. The stream system was set as the target of the computation (STR), to be representative of intense rainfall-runoff events with effective sediment delivery outside the catchments. Output normalization (AICN) allows comparing the results of the five basins between them. The sedimentological analysis is based on specific sediment yield (SSY) -measured at the check-dams installed after the fire -, and this data is used for output evaluation. Stream density and slope variables were the most influential factors on AICN-STR results at the sub-catchment scale. Post-fire hillslope treatments (barriers when built in high densities and afforestation) significantly reduced AICN-STR in comparison with untreated areas in both structural and functional approaches. Despite the presence of hillslope treatments, the higher erosive rainfall conditions resulted in higher AICN-STR values in the Post-man scenario (functional approach). A positive and good correlation was found between the measured SSY and the AICN-STR changes due to the post-fire practices and vegetation recovery, showing the good correspondence of the computation results and the real sediment dynamics of the studied catchments. Overall, AICN demonstrated to be a useful and versatile tool for post-fire management, which needs further research to optimize its applicability.

Interplay between psychosocial and heart failure related factors may partially explain limitations in self-efficacy in patients with heart failure: Insights from a real-world cohort of 1,123 patients.

BACKGROUND AND AIMS: Worse self-care is associated with a higher risk of readmission and mortality in patients with heart failure (HF). Little is known about how the interplay between clinical and psycho-social factors may modulate self-care behaviours in these patients. The aim of our study was to identify clinical, and particularly psycho-social factors associated with worse self-care and assess their interaction inpatients with heart failure. METHODS AND RESULTS: We conducted an observational, prospective, cohort study of 1,123 consecutive patients with chronic heart failure. Self-care was assessed with the modified European Heart Failure Self-care Behavior Scale 9-item version (EHFSCBS-9), and both clinical and psycho-social profile of the patients included were also meticulously evaluated. A total of 484 patients (43%) were women, mean age was 72 years, and mean left ventricular ejection fraction was 44.5%. In multivariable analyses combining clinical and psycho-social factors, low social support (OR 3.53, 95% CI [2.13-5.86]; p-value <0.001), absence of caregiver support (OR 2.16, 95% CI [1.34 -3.48]; p-value 0.001) and depressive symptoms (OR 2.40, 95% CI [1.53-3.77]; p-value <0.001) were independent determinants of impaired global self-care. Advanced functional class was associated with better self-care (OR 0.43, 95%CI [0.26-0.70]; p-value 0.001). No other clinical factors remained significantly associated with self-care in these joint models. In discrimination analyses, models containing psycho-social determinants outperformed models only containing heart failure -related (clinical) variables (all p-values<0.001). CONCLUSION: Impairment in self-care behaviour is strongly determined by psycho-social factors. Specifically, low social support, the lack of caregiver support and the presence of depressive symptoms are the main drivers of the risk of impairment of self-care in heart failure patients. Evaluation of self-care and self-care interventions should be complemented by a comprehensive psycho-social assessment in patients with heart failure. ABBREVIATIONS: DAMOCLES, Definition of the neuro-hormonal Activation, Myocardial function, genOmic expressionand CLinical outcomes in hEart failure patients; NYHA, New York Heart Failure Association; GAM, Generalized Additive Model; BMI, Body Mass Index; GDS, GeriatricDepression Scale.

[Recommendations to develop Care Models for patients with Heart Failure (MAIC Project) from macromanagement]. / Recomendaciones para desarrollar Modelos Asistenciales de atención al paciente con Insuficiencia Cardiaca (Proyecto MAIC): Estudio Delphi.

BACKGROUND: The general objective of the study was to reflect on the key factors to advance in optimal models of care for Heart Failure (HF) and specifically, on the macromanagement elements most necessary for the development of comprehensive HF management models. MATERIAL AND METHODS: An Advisory Committee, composed of 15 experts and a multidisciplinary group of 31 additional experts, was appointed, together forming a Delphi panel of 46 experts. Based on a systematic bibliographic review and the analysis of the care course of the patient with HF, an initial battery of key factors for the development of HF care models was identified by the Advisory Committee. This proposal was adjusted and prioritized by the Delphi panel applying Delphi Rand/UCLA methodology. RESULTS: After two Delphi rounds, 75 key factors grouped into 7 challenges were defined. In the first of the challenges, related to the development of HF management models, 16 key factors were identified, 7 of which were valued as high priority and related to the establishment of common objectives, resources for the continuity of care and improving the measurement of health outcomes. CONCLUSIONS: The definition of management elements at the macro level was considered a priority to advance in the development of optimal models of assistance to HF.

Neoplastic meningitis in solid tumours: updated review of diagnosis, prognosis, therapeutic management, and future directions.

Neoplastic meningitis (NM) is a relatively frequent metastatic complication of cancer associated with high levels of neurological morbidity and generally poor prognosis. It appears in 5%-15% of patients with solid tumours, the most frequent being breast and lung cancer and melanoma. Symptoms are caused by involvement of the cerebral hemispheres, cranial nerves, spinal cord, and nerve roots, and are often multifocal or present with signs and symptoms of intracranial hypertension. The main diagnostic tools are the neurological examination, brain and spinal cord contrast-enhanced magnetic resonance imaging, and cerebrospinal fluid analysis including cytology, although studies have recently been conducted into the detection of tumour cells and DNA in the cerebrospinal fluid, which increases diagnostic sensitivity. With the currently available therapies, treatment aims not to cure the disease, but to delay and ameliorate the symptoms and to preserve quality of life. Treatment of NM involves a multimodal approach that may include radiotherapy, intrathecal and/or systemic chemotherapy, and surgery. Treatment should be individualised, and is based mainly on clinical practice guidelines and expert opinion. Promising clinical trials are currently being conducted to evaluate drugs with molecular and immunotherapeutic targets. This article is an updated review of NM epidemiology, clinical presentation, diagnosis, prognosis, management, and treatment; it is aimed at general neurologists and particularly at neurologists practicing in hospital settings with oncological patients.

Parkinson's disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration.

A deeper understanding of early disease mechanisms occurring in Parkinson's disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients' networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases.

Thyroid surgery in pediatric patients: causes and results. / Cirugía tiroidea en la edad pediátrica: causas y resultados.

OBJECTIVE: Even though thyroid surgery is rare in pediatric patients, frequency has increased in the last years. The objective of this study was to analyze the causes and results of these procedures in a pediatric surgical facility. PATIENTS AND METHODS: Retrospective study including all patients requiring thyroid surgery in our department from 2000 to 2019. Demographic data, diagnostic data, associated pathology, type of surgical procedure, pathological results, and intraoperative and postoperative complications were recorded. RESULTS: 47 patients with a mean age of 8.9 ± 3.9 years at surgery were included. The most frequent diagnosis was MEN syndrome (n = 30, 29 MEN 2A and 1 MEN 2B), followed by thyroid papillary carcinoma (n = 5), follicular adenoma (n = 5), multinodular goiter (n = 4), follicular carcinoma (n = 1), thyroglossal duct papillary carcinoma (n = 1), and Graves-Basedow syndrome (n = 1). 38 total thyroidectomies (73.7% of which were prophylactic), 3 double hemithyroidectomies, 5 hemithyroidectomies, and 5 lymphadenectomies were performed. No intraoperative complications or recurrent laryngeal nerve lesions were noted. Mean postoperative hospital stay was 1.3 ± 0.6 days. 7 patients had transitory asymptomatic hypoparathyroidism, and 1 patient had persistent symptomatic hypoparathyroidism. Pathological results of prophylactic thyroidectomies were: 18 C cell hyperplasias, 7 microcarcinomas, and 3 cases without histopathological disorders. CONCLUSIONS: Thyroid surgery in pediatric patients is safe if performed by specialized personnel. Even though it remains rare, frequency has increased in the last years.

OBJETIVO: La cirugía tiroidea es poco frecuente en la edad pediátrica, aunque ha aumentado su frecuencia en los últimos años. El objetivo de este estudio es analizar las causas y los resultados de estos procedimientos en un centro quirúrgico pediátrico. METODOS: Estudio retrospectivo que incluyó a todos los pacientes que necesitaron cirugía tiroidea en nuestro servicio entre 2000-2019. Se recogieron datos demográficos, diagnóstico, patología asociada, tipo de procedimiento quirúrgico realizado, resultados anatomopatológicos y complicaciones intra y posoperatorias. RESULTADOS: Se incluyeron 47 pacientes con una edad media en el momento de la intervención de 8,9 ± 3,9 años. El diagnóstico más frecuente fue síndrome MEN2 (n = 30, 29 MEN2A y 1 MEN2B), seguido de carcinoma papilar de tiroides (n = 5), adenoma folicular (n = 5), bocio multinodular (n = 4), carcinoma folicular (n = 1), carcinoma papilar del conducto tirogloso (n = 1) y síndrome de Graves-Basedow (n = 1). Se realizaron 38 tiroidectomías totales (el 73,7% fueron profilácticas), tres dobles hemitiroidectomías, cinco hemitiroidectomías y en cinco casos fue necesario realizar una linfadenectomía. No se presentaron complicaciones intraoperatorias ni lesiones de nervio laríngeo recurrente. La estancia media posoperatoria fue de 1,3 ± 0,6 días. Siete pacientes presentaron hipoparatiroidismo transitorio asintomático y en un caso, persistente sintomático. Los resultados anatomopatológicos de las tiroidectomías profilácticas fueron: 18 hiperplasias de células C, 7 microcarcinomas y 3 sin alteraciones histopatológicas. CONCLUSIONES: La cirugía tiroidea en la edad pediátrica es segura en manos de equipos especializados. Aunque sigue siendo un procedimiento poco habitual, su frecuencia está aumentando en los últimos años.

Access to Meckel's cave for biopsies of indeterminate lesions: a systematic review.

Accessing Meckel's cave (MC) is surgically challenging. Open approaches are complex and often correlated with high morbidity. Endoscopic approaches emerged in the last decade as feasible alternatives to open approaches, especially for sampling indeterminate lesions. This article first analyses available routes to approach Meckel's cave and presents furthermore an illustrative case. We conducted a systematic review and reported according to the guidelines for preferred reporting items for systematic reviews and meta-analyses (PRISMA). Various surgical approaches identified through the search are evaluated and discussed in detail. Additionally, we report on a case of woman with a lesion in MC, which was accessed through an endoscopic transpterygoid approach subsequently diagnosed as a diffuse large B cell lymphoma. Our search delivered 75 articles that included case reports (n = 21), cadaveric studies (n = 32), clinical articles (n = 16), review of the literatures (n = 3), as well as technical notes (n = 2) and a radiological manuscript (n = 1). Open routes included lateral approaches with many variations, mainly intra- and extradural pterional approaches and anterior petrosal, as well as a retrosigmoid intradural suprameatal and a lateral transorbital approach. Endoscopically, MC was reached via approaches that included transpterygoid, transorbital or infraorbital fissure routes. Percutaneous approaches, e.g. through the foramen ovale, were also described. Multiple surgical approaches to MC are currently available. Their different characteristics as well as individual patient factors, such as clinical history and the localization of the disease, have to be considered when choosing a surgical corridor. Studies included in this review highlight the endonasal endoscopic transpterygoidal technique as an excellent corridor for biopsies in the ventral MC.

Predictors of success of high-flow nasal cannula in the treatment of acute hypoxemic respiratory failure. / Predictores de éxito del tratamiento con cánula nasal de alto flujo en el fallo respiratorio agudo hipoxémico.

BACKGROUND: High-flow nasal cannula (HFNC) therapy is used in the treatment of acute respiratory failure (ARF) and is both safe and effective in reversing hypoxemia. In order to minimize mortality and clinical complications associated to this practice, a series of tools must be developed to allow early detection of failure. The present study was carried out to: (i)examine the impact of respiratory rate (RR), peripheral oxygen saturation (SpO2), ROX index (ROXI=[SpO2/FiO2]/RR) and oxygen inspired fraction (FiO2) on the success of HFNC in patients with hypoxemic ARF; and (ii)analyze the length of stay and mortality in the ICU, and the need for mechanical ventilation (MV). METHODS: A retrospective study was carried out in the medical-surgical ICU of Hospital de Montilla (Córdoba, Spain). Patients diagnosed with hypoxemic ARF and treated with HFNC from January 2016 to January 2018 were included. RESULTS: Out of 27 patients diagnosed with ARF, 19 (70.37%) had hypoxemic ARF. Fifteen of them (78.95%) responded satisfactorily to HFNC, while four (21.05%) failed. After two hours of treatment, RR proved to be the best predictor of success (area under the ROC curve [AUROC] 0.858; 95%CI: 0.63-1.05; P=.035). For this parameter, the optimal cutoff point was 29rpm (sensitivity 75%, specificity 87%). After 8hours of treatment, FiO2 and ROXI were reliable predictors of success (FiO2: AUROC 0.95; 95%CI: 0.85-1.04; P=.007 and ROXI: AUROC 0.967; 95%CI: 0.886-1.047; P=.005). In the case of FiO2 the optimal cutoff point was 0.59 (sensitivity 75%, specificity 93%), while the best cutoff point for ROXI was 5.98 (sensitivity 100%, specificity 75%). Using a Cox regression model, we found RR<29rpm after two hours of treatment, and FiO2<0.59 and ROXI>5.98 after 8hours of treatment, to be associated with a lesser risk of MV (RR: HR 0.103; 95%CI: 0.11-0.99; P=.05; FiO2: HR 0.053; 95%CI: 0.005-0.52; P=.012; and ROXI: HR 0.077; 95%CI: 0.008-0.755; P=.028, respectively). CONCLUSIONS: RR after two hours of treatment, and FiO2 and ROXI after 8hours of treatment, were the best predictors of success of HFNC. RR<29rpm, FiO2<0.59 and ROXI>5.98 were associated with a lesser risk of MV.

Risk-assessment in chronic subdural hematoma evaluated in 148 patients - A score for predicting recurrence.

BACKGROUND: Chronic subdural hematoma (CSDH) is a frequent disease in neurosurgical practice. However, a considerable recurrence rate keeps this condition challenging to treat. We aimed to provide a simple tool for risk assessment in these patients. METHODS: We conducted a retrospective analysis of surgically treated patients with chronic subdural hematomas. In addition to patients' demographics, radiological assessment included volume, thickness, midline shift and density of hematomas. Statistically significant variables in univariate analysis were further analyzed in a multivariate logistic regression model to create a risk score for recurrence of CSDH. RESULTS: A total of 148 patients were identified and included for analysis. 50.7 % (n = 75) were older than 76 years of age. The overall hematoma recurrence rate requiring surgery was 23.6 % (n = 35). Preoperative thrombocytopenia, postoperative midline shift >6 mm, hematoma volume >80 mL and overall hematoma density >45 Hounsfield Units (HU), were significantly more frequent in the recurrence group. Furthermore, after multivariate assessment, postoperative hematoma density and volume were independent risk factors and included in the risk assessment tool. Patients were divided into 3 risk groups corresponding to the total scores. CONCLUSION: We provide a risk-score assessment for predicting recurrence of subdural hematoma. The risk-score comprises postoperative hematoma volume and density. This tool could ease decision making in follow-up evaluation and indication for recurrence surgery. Yet, further prospective evaluation is required to assess the clinical value of this tool.

Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study.

INTRODUCTION: To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. METHODS: Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. RESULTS: Median age was 64 years (range: 19-84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. CONCLUSIONS: Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.

Neoplastic meningitis in solid tumours: Updated review of diagnosis, prognosis, therapeutic management, and future directions. / Meningitis neoplásica en tumores sólidos: revisión actualizada de diagnóstico, pronóstico, manejo terapéutico y direcciones futuras.

Neoplastic meningitis (NM) is a relatively frequent metastatic complication of cancer associated with high levels of neurological morbidity and generally poor prognosis. It appears in 5%-15% of patients with solid tumours, the most frequent being breast and lung cancer and melanoma. Symptoms are caused by involvement of the cerebral hemispheres, cranial nerves, spinal cord, and nerve roots, and are often multifocal or present with signs and symptoms of intracranial hypertension. The main diagnostic tools are the neurological examination, brain and spinal cord contrast-enhanced magnetic resonance imaging, and cerebrospinal fluid analysis including cytology, although studies have recently been conducted into the detection of tumour cells and DNA in the cerebrospinal fluid, which increases diagnostic sensitivity. With the currently available therapies, treatment aims not to cure the disease, but to delay and ameliorate the symptoms and to preserve quality of life. Treatment of NM involves a multimodal approach that may include radiotherapy, intrathecal and/or systemic chemotherapy, and surgery. Treatment should be individualised, and is based mainly on clinical practice guidelines and expert opinion. Promising clinical trials are currently being conducted to evaluate drugs with molecular and immunotherapeutic targets. This article is an updated review of NM epidemiology, clinical presentation, diagnosis, prognosis, management, and treatment; it is aimed at general neurologists and particularly at neurologists practicing in hospital settings with oncological patients.

Maternal nutrient restriction in early pregnancy increases the risk of late embryo loss despite no effects on peri-implantation interferon-stimulated genes in suckler beef cattle.

Reducing feeding costs in suckler beef herds to improve economic returns could have detrimental impacts on fertility. This study sought to determine whether maternal nutrient restriction during early pregnancy affects interferon-stimulated gene (ISG) expression in peripheral blood mononuclear cells during the peri-implantation period in two beef cattle breeds. Relationships were also examined between subnutrition and pregnancy failure defined according to ISG fold changes on Days 18 and 21 and to plasma pregnancy specific protein B (PSPB) concentrations on Day 28 post-artificial insemination (AI). Pirenaica or Parda de Montaña dams were assigned to a control (n = 23) or subnutrition (n = 30) group, receiving 100% or 65% of their estimated nutritional requirements from Day 1 to 82 post-AI, respectively. Treatment did not affect ISG expression or fertility. According to ISG fold changes (chi-square P = .023) or PSPB levels (chi-square P = .04) recorded in the subnutrition group, late embryo loss was more likely than in controls. Positive correlation was detected between Day 28 PSPB concentrations and both Day 18 MX1, MX2 and ISG15 expression, and Day 21 OAS1 expression. OAS1 and MX1 fold changes were found to be the best variables to discriminate pregnancy status. Our findings indicate that maternal nutrient restriction during the first third of pregnancy does not impair embryo signalling yet may increase the risk of pregnancy failure.

Development and validation of a brief electronic screening test for cognitive impairment in multiple sclerosis (SCI-MS Test).

OBJECTIVE: Although cognitive impairment (CI) is common in multiple sclerosis (MS), it is difficult to suspect in patients with low disability and there is a lack of brief and effective CI screening tools with a define cut-off point to be used during routine clinic visits. This study aims to validate the Electronic Screening Cognitive Impairment in Multiple Sclerosis (SCI-MS) test for CI among MS patients. METHODS: Cross-sectional, observational study that included adult patients, diagnosed with MS, Expanded Disability Status Scale (EDSS) score ≤6.5, without relapses within the last 2 months and no depression symptoms. The SCI-MS test consists of two modules: questionnaire (SCI-MS-Q) and pictogram matching tool (SCI-MS-P) measured for score and time. At inclusion, patients completed the Beck Depression Inventory (BDI-II test), the Brief Repeatable Battery of Neuropsychological Test (BRB-N) and the SCI-MS. The SCI-MS feasibility, test-retest reliability and predictive validity were assessed. RESULTS: A total of 194 patients (59.3% female) were included: mean (SD) age of 42 (9) years, mean time since diagnosis of 10 (7) years, 89.7% relapsing-remitting MS, and median (Q1-Q3) EDSS of 2.0 (1.0-3.5). According to BRB-N, 26.8% of patients had CI. Internal consistency was high (Cronbach alpha: 0.97). The intra-class correlation coefficient was 0.88 for the SCI-MS-Q, 0.09 for the SCI-MS-P score and 0.48 for the SCI-MS-P time, corresponding to AUC of the ROC curves of 0.571, 0.574 and 0.714, respectively. For a clinically significant cut-off point of ≥60 seconds, the reached CI sensitivity of SCI-MS-P time was 0.75 and the specificity 0.51. CONCLUSION: SCI-MS showed good psychometric properties. SCI-MS-P time of pictogram completion had an acceptable diagnostic accuracy of CI in MS patients with low disability. SCI-MS-P time of pictogram completion tool is an easy and quick score that can help neurologists to early identify CI in MS patients that should be further assessed to confirm CI diagnosis and to describe its characteristics and mainly affected domains.