[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.

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.

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.

Evaluation of haematological, serum biochemical and histopathological parameters of growing rabbits fed Amaranthus dubius.

Amaranthus dubius is an alternative source of fibre and protein for the feed formulation for growing rabbits, although its effects on their health status are yet unknown. Therefore, this study aimed to evaluate the effects of three dietary levels (0, 160 and 320 g/kg) of A. dubius on haematological, serum biochemical and histopathological parameters of fattening rabbits. One hundred and thirteen New Zealand White rabbits were fed ad libitum from weaning (35 days) to slaughter (87 days). The health status of the animals was monitored, and mortality was recorded. Before slaughtering, 30 rabbits were randomly selected for haematological and serum biochemical analysis. During slaughter, 18 rabbits were randomly selected for histopathological study in heart, liver, lung and small intestine. The health status of rabbits was good, with no differences among treatments in mortality. Diet and sex did not affect the values of most haematological and serum biochemical parameters. Fibrinogen, glucose and high-density lipoprotein values increased significantly from 0 to 320 g/kg A. dubius diets. The white blood cell count and glutamic oxaloacetic transaminase values decreased significantly from 0 to 320 g/kg A. dubius diets. The organs showed histologically well-structured tissues. However, in all experimental groups several samples with lesions were observed, always highly focalized in small tissue areas. The main lesions observed, probably related to conditions of thermal stress affecting the rabbits, were cholesterolosis (heart), steatosis (liver), inflammatory lymphoplasmacytic infiltrate (lung) and chronic inflammatory tissue damage (small intestine). In conclusion, the inclusion of up to 320 g/kg A. dubius in diet did not jeopardize the health status of growing rabbits. Therefore, A. dubius can become an alternative raw material for the formulation of feeds in tropical and subtropical countries where this plant is widespread.

Hydrolysed ovalbumin offers more effective preventive and therapeutic protection against egg allergy than the intact protein.

BACKGROUND: The application of specific immunotherapy to stimulate oral tolerance towards food allergens is hampered by the high frequency of adverse side-effects and the excessive duration of the treatments. OBJECTIVE: In this work, a hydrolysate of ovalbumin with pepsin (OP), selected for its low IgE reactivity and Th2-stimulating capacity, was assayed for its ability to prevent and treat allergy to egg white (EW). METHODS: As a first step, the safety of OP, in terms of the absence of sensitizing and eliciting potential, was evaluated in BALB/c mice. Then, its suitability for prophylactic and therapeutic applications was compared with that of the intact allergen, paying attention to the molecular and cellular mechanisms involved in the control of the allergic process. To this aim, IgE, IgG1, IgG2a and IgA levels, allergic reactions, expression of genes related to Th1, Th2, Th17 and Treg responses, dendritic and T cell populations were assessed in intestinal tissues and spleens of EW-allergic mice, either untreated or treated with intact ovalbumin (OVA) or OP. RESULTS: The hydrolysate of OVA with pepsin was hypoallergenic, lacked sensitizing potential and offered preventive and therapeutic protection against allergy to EW through the induction of Treg cells and the up-regulation of TGF-ß, IL-10, IL-17, Foxp3 and RORγt in intestinal tissues. This restrained the expression of GATA3 and the differentiation of Th2 cells, leading to low cytokine responses following ex vivo spleen cell stimulation. As compared with intact OVA, OP was more effective against sensitization. In addition, in the therapeutic setting, OP provided quicker desensitization that lasted for at least 3 weeks after discontinuation of the therapy. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides evidence for the superior role of hydrolysed, as compared to intact allergens, in the prevention of allergy development and in the promotion of long-term desensitization, as well as of intermolecular tolerance.

[Pleural cavity concerns]. / Los quebraderos de cabeza del espacio pleural.

INTRODUCTION: Persistent air leak (PAL) is a common problem. We asses our experience in the management of these patients. MATERIAL AND METHODS: Retrospective review of patients with chest tubes after bronchopulmonary pneumothorax (due to lung resections, spontaneous pneumothorax, necrotizing pneumonia) from 2010 to 2015. We studied clinical data, PAL incidence, risk factors and treatment, considering PAL ≥ 5 days. RESULTS: Thirty-seven cases (28 patients) between 0-16years: 26 lung resections, 11 pneumothorax. We found no differences in the distribution of age, weight, indication or comorbidity, but we noticed a trend to shorter hospital stay in infants. Patients with staple-line reinforcement presented lower PAL incidence than patients with no mechanical suture (43% vs 37%), the difference is even apparent when applying tissue sealants (29% vs 50%) (p > 0.05). We encountered no relationship between the size of the tube (10-24 Fr) or the type of resection, with bigger air leaks the higher suction pressure. We performed 13 pleurodesis in 7 patients (2 lobectomies, 3 segmentectomies and 2 bronchopleural fistulas), with 70% effectiveness. We conducted 7 procedures with autologous blood (1.6 ml/kg), 2 with povidone-iodine (0.5 ml/kg), 2 mechanical thoracoscopic and 2 open ones. We repeated pleurodesis four times, 3 of them after autologous blood infusion: 2 infusions with the same dose (both effective) and the other 2 as thoracotomy in patients with bronchopleural fistulas. After instillation of blood 3 patients presented with fever. After povidone-iodine instillation, the patient suffered from fever and rash. CONCLUSIONS: Intraoperative technical aspects are essential to reduce the risk of PAL. Autologous blood pleurodesis, single or repeated, is a minimal invasive option, very safe and effective to treat the parenchymatous PAL.

INTRODUCCION: La fuga aérea persistente (FAP) es un problema común. Evaluamos nuestra experiencia en el manejo de estos pacientes. MATERIAL Y METODOS: Revisión retrospectiva 2010-2015 de pacientes con drenaje endotorácico por neumotórax broncopulmonar (resecciones pulmonares, neumotórax, neumonía necrotizante). Revisamos datos clínicos, incidencia de FAP, factores determinantes y tratamiento, considerando FAP ≥ 5 días. RESULTADOS: Treinta y siete casos (28 pacientes) con edades entre 0-16 años: 26 resecciones pulmonares, 11 neumotórax. No encontramos diferencias en distribución de edad, peso, indicación quirúrgica ni comorbilidad, aunque sí tendencia a menor estancia hospitalaria en lactantes. Los pacientes con sutura no mecánica presentaron más fugas que los pacientes con sutura mecánica (43 vs 37%), así como los pacientes a los que no se aplicaron sellantes tisulares (29 vs 50%) (ambos p > 0,05). No encontramos relación con el tamaño del tubo (10-24 Fr) ni con el tipo de resección, manteniendo más fuga aérea los de mayor presión de aspiración. Realizamos 13 pleurodesis en 7 pacientes (2 lobectomías, 3 segmentectomías y 2 fístulas broncopleurales), con efectividad del 70%. Realizamos 7 con sangre autóloga (1,6 ml/kg), 2 con povidona iodada (0,5 ml/kg), 2 mecánicas toracoscópicas y 2 abiertas. Se repitió la pleurodesis en 4 ocasiones, 3 de ellas tras sangre autóloga: dos con repetición de la misma dosis (ambas efectivas) y otras dos por toracotomía en los pacientes con fístula broncopleural. Tras la instilación de sangre 3 casos presentaron fiebre. Tras la de povidona iodada, fiebre y exantema. CONCLUSIONES: Los aspectos técnicos intraoperatorios son esenciales para disminuir el riesgo de FAP. La pleurodesis con sangre autóloga, única o repetida, es una opción poco invasiva, muy segura y efectiva para las FAP parenquimatosas en nuestra muestra.

Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1.

Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy.

Size control of in vitro synthesized magnetite crystals by the MamC protein of Magnetococcus marinus strain MC-1.

Magnetotactic bacteria are a diverse group of prokaryotes that share the unique ability of biomineralizing magnetosomes, which are intracellular, membrane-bounded crystals of either magnetite (Fe3O4) or greigite (Fe3S4). Magnetosome biomineralization is mediated by a number of specific proteins, many of which are localized in the magnetosome membrane, and thus is under strict genetic control. Several studies have partially elucidated the effects of a number of these magnetosome-associated proteins in the control of the size of magnetosome magnetite crystals. However, the effect of MamC, one of the most abundant proteins in the magnetosome membrane, remains unclear. In this present study, magnetite nanoparticles were synthesized inorganically in free-drift experiments at 25 °C in the presence of different concentrations of the iron-binding recombinant proteins MamC and MamCnts (MamC without its first transmembrane segment) from the marine, magnetotactic bacterium Magnetococcus marinus strain MC-1 and three commercial proteins [α-lactalbumin (α-Lac), myoglobin (Myo), and lysozyme (Lyz)]. While no effect was observed on the size of magnetite crystals formed in the presence of the commercial proteins, biomimetic synthesis in the presence of MamC and MamCnts at concentrations of 10-60 µg/mL resulted in the production of larger and more well-developed magnetite crystals (~30-40 nm) compared to those of the control (~20-30 nm; magnetite crystals grown protein-free). Our results demonstrate that MamC plays an important role in the control of the size of magnetite crystals and could be utilized in biomimetic synthesis of magnetite nanocrystals.

[Intensive chemotherapy for Burkitt lymphoma in HIV positive patients]. / Linfoma de Burkitt en pacientes HIV positivo tratados con quimioterapia intensiva en el Hospital del Salvador entre 2011 y 2014: Protocolo Nacional de Cáncer del Adulto, Chile.

BACKGROUND: Burkitt lymphoma has a low incidence, is highly aggressive, may be endemic, sporadic or associated with immunodeficiency and it has a high frequency of extranodal involvement. Overall and relapse free survival in HIV patients is 72 and 71% respectively. However, the current protocol in Chile considers a positive HIV serology as an exclusion criterion for intensive chemotherapy. AIM: To analyze the response to Burkitt lymphoma treatment among HIV positive patients. MATERIAL AND METHODS: All HIV positive patients with a Burkitt lymphoma treated using PANDA protocol in a public hospital were analyzed. RESULTS: Eight male patients aged between 25 and 43 years, 63% in stage IV, were analyzed. All patients received an intensified chemotherapy regime, three of them without Rituximab. Complete remission was achieved in 87%. One patient was refractory to treatment and one patient relapsed at 5 months and died. Overall and relapse free survival were 58 and 60% respectively. All patients had episodes of high risk febrile neutropenia, but it did not cause deaths. CONCLUSIONS: In this group of HIV patients, intensive chemotherapy for Burkitt lymphoma had a high degree of effectiveness with a low relapse rate and high cure rate.

[Fast track protocol for children undergoing appendicectomy]. / Protocolo de alta precoz tras apendicectomía en niños.

BACKGROUND: Multiple approaches to the treatment of simple and complicated (gangrenous or perforated) appendicitis in children have been promoted. Our goal is to develop a new protocol for these patients that allows shorter hospital stays without increasing complications rates. METHODS: Prospective collected data of patients undergoing appendicitis treated according to the new protocol for a period of 7 months were reviewed. This protocol consists on antibiotic prophylaxis in all cases continued with triple antibiotic regimen in complicated appendicitis. Antibiotics were stopped when specific clinical and laboratory criteria were met. Outcomes are compared to a historical group of patients treated under standard protocol (antibiotic prophylaxis followed by 48 hours of dual antibiotic therapy in simple appendicitis or 5 day-course of triple antibiotic therapy in complicated as postooperative antibiotic regimen). RESULTS: A total of 196 patients (96 current group and 100 historical group) were reviewed. In simple appendicitis average length of postoperative hospitalization was significantly lower in the current group (no statistical difference). 52.9% of complicated appendicitis in the current group were discharged home before 5th day without increasing the complication rate. When a wound infection or intraabdominal abscess occurs thrombocytosis (52%) and prolonged vomiting are the most frequent symptoms. CONCLUSION: No further postoperative treatment is needed in simple appendicitis. In complicated appendictis a short course of antibiotics according to clinical and laboratory criteria allows early discharge without major morbidity. Prolonged postoperative vomiting and thrombocytosis suggest infectious complications.

OBJETIVOS: Existen múltiples modalidades de tratamiento antibioterápico tras una apendicectomía en niños. Nuestro objetivo es desarrollar un nuevo protocolo para el tratamiento de las apendicitis que permita acortar la estancia hospitalaria sin aumentar las complicaciones. MATERIAL Y METODOS: Estudio prospectivo que analiza a los pacientes intervenidos de apendicitis tratados según el nuevo protocolo de antibioterapia durante un periodo de 7 meses. Dicho protocolo consiste en profilaxis quirúrgica en todos los casos y continuar con triple antibioterapia en las evolucionadas, con una duración variable según criterios clínico-analíticos establecidos previamente. Se comparan los resultados con los de un grupo histórico de pacientes tratados con el protocolo clásico (profilaxis y 48 horas de doble antibioterapia en las flemonosas y 5 días de triple en las evolucionadas). RESULTADOS: Se estudian un total de 196 pacientes (96 grupo actual y 100 grupo histórico). En las apendicitis flemonosas la estancia hospitalaria postquirúrgica media es significativamente menor en el grupo actual sin encontrar diferencias estadísticas en la tasa de complicaciones. El 52,9% de las apendicitis evolucionadas del grupo actual fueron dadas de alta antes del 5º día sin aumentar la tasa de complicaciones. De los pacientes que presentaron una complicación infecciosa el 52% asociaban trombocitosis y la clínica más frecuente fue de vómitos prolongados. CONCLUSIONES: No es necesario tratamiento antibioterápico postoperatorio en apendicitis simples. En las evolucionadas un tratamiento corto de antibióticos según criterios clínico-analíticos permite un alta precoz sin mayor morbilidad asociada. Los vómitos prolongados y la trombocitosis son indicadores de complicaciones infecciosas postoperatorias.

A quantitative and humane tail bleeding assay for efficacy evaluation of antihaemophilic factors in haemophilia A mice.

The tail bleeding model using haemophilic mice has been used as one of the standard assays for efficacy evaluation of novel antihaemophilic therapies at the preclinical level. A number of different configurations and endpoints have been proposed in the literature for this model, hindering interlaboratory comparisons. A particular configuration, known as the tail bleeding survival assay (TBS), adopted by several groups, involves measuring the ability of conscious haemophilic mice to survive exsanguination following tail transection. Major limitations to this configuration include ethical constraints and impaired quantitative determinations. The aim of this study was to standardize and validate a quantitative haemostatic assay for evaluation of antihaemophilic therapies employing an alternative to TBS, which involves a more humane endpoint associated with stable clot formation. Haemophilic mice were treated with vehicle or different doses of two antihaemophilic reference products licensed in Brazil. The haemostatic response was evaluated by our quantitative tail bleeding haemostatic assay (qTBA) over a period of 120 min and then quantified by dose-response modelling. We demonstrate that our qTBA method allows a direct relationship between the number of animals which achieved full haemostatic response and the dosage of both antihaemophilic factors evaluated over 120 min. In addition, the method sensitivity is suitable to demonstrate the conversion from a severe to a moderate haemophilia phenotype. Our proposed qTBA is easy to implement and constitutes an alternative and more ethical endpoint, which could be effectively used as a surrogate to the commonly employed survival endpoint, allowing quantitative haemostatic response evaluation associated with stable clot formation.

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.

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.

A study of the SCN5A gene in a cohort of 76 patients with Brugada syndrome.

We aim to study the SCN5A gene in a cohort of Brugada syndrome (BS) patients and evaluate the genotype-phenotype correlation. BS is caused by mutations in up to 10 different genes, SCN5A being the most frequently involved. Large genomic rearrangements in SCN5A have been associated with conduction disease, but its prevalence in BS is unknown. Seventy-six non-related patients with BS were studied. Clinical characteristics and family risk profile were recorded. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) of the SCN5A gene for identification of mutations and larger rearrangements were performed, respectively. Eight patients (10.5%) had point mutations (R27H, E901K, G1743R (detected in three families), V728I, N1443S and E1152X). Patients with mutations had a trend toward a higher proportion of spontaneous type I Brugada electrocardiogram (ECG) (87.5% vs 52.9%, p = 0.06) and had evidence of familial disease (62.5%, vs 23.5%, p = 0.03). The symptoms and risk profile of the carriers were not different from wild-type probands. There were non-significant differences in the prevalence of type I ECG, syncope and history of arrhythmia in carriers of selected polymorphisms. None of the patients had any deletion/duplication in the SCN5A gene. In conclusion, 10.5% of our patients had mutations in the SCN5A gene. Patients with mutations seemed to have more spontaneous type I ECG, but no differences in syncope or arrhythmic events compared with patients without mutations. Larger studies are needed to evaluate the role of polymorphisms in the SCN5A in the expression of the phenotype and prognosis. Large rearrangements were not identified in the SCN5A gene using the MLPA technique.

Comprehensive model of microalgae photosynthesis rate as a function of culture conditions in photobioreactors.

In this paper, the influence of culture conditions (irradiance, temperature, pH, and dissolved oxygen) on the photosynthesis rate of Scenedesmus almeriensis cultures is analyzed. Short-run experiments were performed to study cell response to variations in culture conditions, which take place in changing environments such as outdoor photobioreactors. Experiments were performed by subjecting diluted samples of cells to different levels of irradiance, temperature, pH, and dissolved oxygen concentration. Results demonstrate the existence of photoinhibition phenomena at irradiances higher than 1,000 µE/m(2) s; in addition to reduced photosynthesis rates at inadequate temperatures or pH-the optimal values being 35 °C and 8, respectively. Moreover, photosynthesis rate reduction at dissolved oxygen concentrations above 20 mg/l is demonstrated. Data have been used to develop an integrated model based on considering the simultaneous influence of irradiance, temperature, pH, and dissolved oxygen. The model fits the experimental results in the range of culture conditions tested, and it was validated using data obtained by the simultaneous variation of two of the modified variables. Furthermore, the model fits experimental results obtained from an outdoor culture of S. almeriensis performed in an open raceway reactor. Results demonstrate that photosynthetic efficiency is modified as a function of culture conditions, and can be used to determine the proximity of culture conditions to optimal values. Optimal conditions found (T = 35 °C, pH = 8, dissolved oxygen concentration <20 mg/l) allows to maximize the use of light by the cells. The developed model is a powerful tool for the optimal design and management of microalgae-based processes, especially outdoors, where the cultures are subject to daily culture condition variations.

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.

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.

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.