Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma.

PURPOSE: B-cell maturation antigen (BCMA)-chimeric antigen receptor T-cells (CART) improve results obtained with conventional therapy in the treatment of relapsed/refractory multiple myeloma. However, the high demand and expensive costs associated with CART therapy might prove unsustainable for health systems. Academic CARTs could potentially overcome these issues. Moreover, response biomarkers and resistance mechanisms need to be identified and addressed to improve efficacy and patient selection. Here, we present clinical and ancillary results of the 60 patients treated with the academic BCMA-CART, ARI0002h, in the CARTBCMA-HCB-01 trial. PATIENTS AND METHODS: We collected apheresis, final product, peripheral blood and bone marrow samples before and after infusion. We assessed BCMA, T-cell subsets, CART kinetics and antibodies, B-cell aplasia, cytokines, and measurable residual disease by next-generation flow cytometry, and correlated these to clinical outcomes. RESULTS: At cut-off date March 17, 2023, with a median follow-up of 23.1 months (95% CI, 9.2-37.1), overall response rate in the first 3 months was 95% [95% confidence interval (CI), 89.5-100]; cytokine release syndrome (CRS) was observed in 90% of patients (5% grades ≥3) and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in 2 patients (3%). Median progression-free survival was 15.8 months (95% CI, 11.5-22.4). Surface BCMA was not predictive of response or survival, but soluble BCMA correlated with worse clinical outcomes and CRS severity. Activation marker HLA-DR in the apheresis was associated with longer progression-free survival and increased exhaustion markers correlated with poorer outcomes. ARI0002h kinetics and loss of B-cell aplasia were not predictive of relapse. CONCLUSIONS: Despite deep and sustained responses achieved with ARI0002h, we identified several biomarkers that correlate with poor outcomes.

[Body mass index and triponderal index in abnormal uterine bleed]. / Índice de masa corporal e índice triponderal en sangrado uterino anormal.

Background: Abnormal uterine bleeding (AUB) is the most common cause of blood loss. Obesity and overweight are risk factors for AUB. Objective: To compare the association between body mass index (BMI) and tri-ponderal mass index (TMI) with the presence of acute AUB and chronic AUB. Material and methods: Observational, cross-sectional and analytical study. Women between 18 and 45 years of age with an alteration in the regular uterine bleeding pattern were included. Postmenopausal women, carriers of an intrauterine device as a method of family planning who have developed alterations in the menstrual rhythm after it, those who suffered from chronic diseases (chronic kidney disease, diabetes mellitus and uncontrolled hypothyroidism) and those with medication consumption that alter coagulation were not included. Pregnant patients were excluded. Results: A total of 292 women with AUB were analyzed, with a median age of 38.5 (IQR 33-41), with bleeding of 205.4 mL (±142.9) and 116 (39.86%) of them with overweight. When analyzing the BMI with SUA, we found no significant difference in the presence of acute or chronic bleeding in the overweight (p = 0.46) and obese (p = 0.41) groups. When analyzing the IMT with the presence of acute or chronic AUB, it was not possible to find a significant difference in the overweight (p = 0.98) and obesity (p = 0.93) groups. Conclusions: The BMI was compared with the TMI for the presence of AUB, without finding a significant association.

Introducción: la hemorragia uterina anormal es la causa más común de pérdida hemática. La obesidad y el sobrepeso son factores de riesgo de sangrado uterino anormal (SUA). Objetivo: comparar la asociación entre el índice de masa corporal (IMC) y el índice de masa triponderal (IMT) con la presencia de SUA agudo y SUA crónico. Material y métodos: estudio observacional, transversal y analítico. Se incluyeron mujeres entre 18 y 45 años con alteración en el patrón de sangrado uterino regular. No se incluyeron mujeres postmenopáusicas, ni las portadoras de un dispositivo intrauterino como método de planificación familiar que hayan desarrollado alteraciones en el ritmo menstrual posterior al mismo, aquellas que padecieran enfermedades crónicas (enfermedad renal crónica, diabetes mellitus e hipotiroidismo en descontrol) ni las que tuvieran consumo de medicamentos que alteraran la coagulación. Se excluyeron pacientes embarazadas. Resultados: se analizaron 292 mujeres con SUA, con una mediana de edad de 38.5 (RIC 33-41), con sangrado de 205.4 mL (± 142.9) y 116 (39.86%) de ellas tenían sobrepeso. Al analizar el IMC con SUA no encontramos diferencia significativa en presencia de sangrado agudo o crónico en los grupos con sobrepeso (p = 0.46) y obesidad (p = 0.41). Al analizar el IMT con la presencia de SUA agudo o crónico, no fue posible encontrar diferencia significativa en los grupos de sobrepeso (p = 0.98) y obesidad (p = 0.93). Conclusiones: se comparó el IMC con el IMT para la presencia de SUA y no se encontró asociación significativa.

Effect of Fish Oil Parenteral Emulsion Supplementation on Inflammatory Parameters after Esophagectomy.

(Background) Esophagectomy (EPG) presents high morbidity and mortality. Omega-3 fatty acids (ω-3FA) are a pharmaconutrient with benefits for postoperative morbidity. Studies of ω-3FA administered parenterally after esophagectomy are scarce. This study proposes to investigate the effect of combining fish oil lipid emulsions (LE) administered parenterally with enteral nutrition support. (Methods) Randomization was 1:1:1 in three groups: Group A received a LE mixture of 0.4 g/kg/day of fish oil and 0.4 g/kg/day of LCT/MCT 50:50, Group B received 0.8 g/kg/day of fish oil LE, and Group C received 0.8 g/kg/day of LCT/MCT 50:50. Variables were measured at recruitment time and day +1, +3, and +5. Inflammatory variables studied were Interlukin-6, C-reactive protein (CRP), tumoral necrosis factor-α (TNF-α), IL-10, IL-8 and CD25s. Safety, nutritional parameters and complications were analyzed. (Results) Administration of ω-3LE in the immediate postoperative period did not modulate the earlier inflammatory response. Statistically significant differences were found in IL-6 and CRP overall temporal evolution but were not found when studying the type of LE administered or in patients needing critical care. Administration of ω-3 resulted in safe and improved hypertriglyceridemia, depending on the dose. (Conclusions) ω-3FA has no impact on the early inflammatory postoperative response assessed for a short period but was safe. More studies for longer periods are needed.

Clinical, randomized, double blind clinical trial to study the effect of parenteral supplementation with fish oil emulsion in the nutritional support in esophagectomized patients.

INTRODUCTION: Esophagectomy is a major surgery with a high degree of catabolic and post-surgical inflammatory response accompanied by high morbidity and significant mortality. Post-surgical nutritional support via enteral administration of ω-3 fatty acids has been seen to be effective although its bad tolerance. There are few clinical trials with parenteral ω-3 fatty acids in these patients. We propose to investigate the effect of combining a parenteral fish oil lipid emulsion with the standard enteral nutrition (EN) support. MATERIALS AND METHODS: Prospective, single-center, randomized, double-blind study in esophagectomized patients, and treated after surgery with parenteral lipid emulsions of ω-3 fatty acids or a mixture of ω-6 long-chain triglycerides/short-chain triglycerides 50%. These emulsions will be added to the standard nutritional support in continuous infusion until 5 days of treatment have been completed. Patients will be randomized 1:1:1 in Group A receiving 0.4 g/kg/d of fish-oil lipid emulsion and 0.4 g/kg/d of a lipid emulsion mixture of ω-6 long-chain fatty acids (LCT) plus medium-chain fatty acids (MCT) (total dose of 0.8 g/kg/d of lipid emulsion); Group B receiving 0.8 g/kg/d of fish oil lipid emulsion and Group C receiving 0.8 g/kg/d of LCT/MCT emulsion.The main objective is to determine whether 5 days administration of intravenous ω-3 fatty acid lipid emulsion is effective in normalizing interleukin-6 levels compared with LCT/MCT emulsions, and whether a 0.8 g/kg/d dose is more effective than 0.4 g/kg/d. Secondary outcomes include other inflammatory markers such as C-reactive protein, tumor necrosis factor alpha and interleukin-10, and parameters of morbidity, safety, nutrition and mortality.Samples will be collected at the time when surgery is indicated and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and safety parameters. In addition, clinical follow-up will be continued throughout the hospital admision and up to 1 year after surgery. DISCUSSION: Studies of ω-3 fatty acids administered parenterally in esophagectomized patients are scarce. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered parenterally with EN support. Potential benefits include fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only 1 pharmaconutrient. TRIAL REGISTRATION: FAR-NP-2017-01 EudraCT number: 2016-004978-17.https://reec.aemps.es/reec/public/detail.html searching the EudraCT number. VERSION IDENTIFIER: Version 2, 08/06/2017.

De grupo de presión a actor político: infraestructuras de paz y madurez del conflicto en Colombia / From Pressure Group to Political Actor: Peace Infrastructures and Maturity of the Conflict in Colombia

Resumen Las infraestructuras de paz, desde su génesis en la administración de Belisario Be tancur, en Colombia, han sido grupos de presión de carácter privado y mixto en me nor medida, que están en una constante lucha por constituirse como un actor políti co con un grado mayor de institucionalización, valiéndose de la movilización social de manera pacífica. Estos grupos de presión a diferencia de los partidos, solo pre tenden influir el sistema político. Se concluye que las infraestructuras de paz, han transitado de ser un grupo de presión a un actor político con participación directa y necesidades puntuales en el posconflicto.

Abstract Peace infrastructure, from its onset under Belisario Betancur's term, in Colombia, has been pressure groups of a private and mixed nature to a lesser extent, which are in a constant struggle to establish themselves as a political actor with a greater degree of institutionalization, by using social mobilization peacefully. These groups of pressure, unlike parties, are only intended to influence the political system. It is concluded that peace infrastructure has gone from being a pressure group to a poli tical actor with direct participation and timely needs in the post-conflict.

Evaluation of nutrients removal (NO3-N, NH3-N and PO4-P) with Chlorella vulgaris, Pseudomonas putida, Bacillus cereus and a consortium of these microorganisms in the treatment of wastewater effluents.

In this research removal of NH3-N, NO3-N and PO4-P nutrients from municipal wastewater was studied, using Chlorella vulgaris, Pseudomonas putida, Bacillus cereus and an artificial consortium of them. The objective is to analyze the performance of these microorganisms and their consortium, which has not been previously studied for nutrient removal in municipal wastewater. A model wastewater was prepared simulating the physicochemical characteristics found at the wastewater plant in Chapala, Mexico. Experiments were carried out without adding an external carbon source. Results indicate that nutrient removal with Chlorella vulgaris was the most efficient with a removal of 24.03% of NO3-N, 80.62% of NH3-N and 4.30% of PO4-P. With Bacillus cereus the results were 8.40% of NO3-N, 28.80% of NH3-N and 3.80% of PO4-P. The removals with Pseudomonas putida were 2.50% of NO3-N, 41.80 of NH3-N and 4.30% of PO4-P. The consortium of Chlorella vulgaris-Bacillus cereus-Pseudomonas putida removed 29.40% of NO3-N, 4.2% of NH3-N and 8.4% of PO4-P. The highest biomass production was with Bacillus cereus (450 mg/l) followed by Pseudomonas putida (444 mg/l), the consortium (205 mg/l) and Chlorella vulgaris (88.9 mg/l). This study highlights the utility of these microorganisms for nutrient removal in wastewater treatments.

Assessment of Pozzolanic Activity Using Methods Based on the Measurement of Electrical Conductivity of Suspensions of Portland Cement and Pozzolan.

The use of methods based on measuring electrical conductivity to assess pozzolanic activity has recently been used primarily in aqueous suspensions of pozzolan: calcium hydroxide. However, the use of similar methods in suspensions of cement with pozzolans has not been widely studied. This paper proposes a new method for rapid assessment of the pozzolanic activity of mineral admixtures in aqueous cement suspensions. In this study, the conditions for the application of the method were optimized, such as time, temperature, w/c ratio and dosage procedure. Finally, results are presented from the application of this method for characterizing the pozzolanic activity of the spent catalytic cracking catalyst. These results corroborate as previously reported, namely the high reactivity of this pozzolan obtained by other methods, such as thermogravimetry or evolution of the mechanical strength. In addition, the pozzolanic activity of the catalyst was compared with other pozzolans such as metakaolin and silica fume.

Assessment of the Pozzolanic Activity of a Spent Catalyst by Conductivity Measurement of Aqueous Suspensions with Calcium Hydroxide.

The pozzolanic activity of the spent catalyst produced by fluid catalytic cracking (FCC) has been studied by various methods in recent years. However, no quick and easy method has been reported for this activity based on the associated studies. In this work, the pozzolanic activity of a spent catalyst was investigated by measuring its electrical conductivity in aqueous suspensions of pozzolan/calcium hydroxide. The behavior of the FCC catalyst residue was compared to that of reactive and inert materials of similar chemical compositions. Further, the influence of temperature on the suspension was studied, and also, a new method was proposed in which the pozzolan/calcium hydroxide ratio was varied (with the initial presence of solid Ca(OH)2 in the system). It was concluded that the method is effective, fast and simple for evaluating the high reactivity of the catalyst. Therefore, this method is an alternative for the evaluation of the reactivity of pozzolanic materials.

Production of platinum nanoparticles and nanoaggregates using Neurospora crassa.

Fungal biomass and fungal extract of the nonpathogenic fungus Neurospora crassa were successfully used as reducing agents for the biosynthesis of platinum nanoparticles (PtNPs). The experiment was carried out by exposing the fungal biomass or the fungal extract to a 0.001 M precursor solution of hexachloroplatinic(IV) acid (H2PtCl6). A change of color of the biomass from pale yellow to dark brown was the first indication of possible formation of PtNPs by the fungus. Subsequent analyses confirmed the intracellular biosynthesis of single PtNPs (4-35 nm in diameter) and spherical nanoaggregates (20-110 nm in diameter). Using the fungal extract, similar results were obtained, producing rounded nanoaggregates of Pt single crystals in the range of 17-76 nm.

Chemical speciation of PM2.5 collected during prescribed fires of the Coconino National Forest near Flagstaff, Arizona.

The use of prescribed fire is expected to increase in an effort to reduce the risk of catastrophic fire, particularly at urban/forest interfaces. Fire is a well-known source of particulate matter (PM) with particle sizes < or =2.5 microm (PM2.5), small diameter PM known to affect climate, visibility, and human health. In this work, PM2.5 was collected during seven first-entry burns (flaming and smoldering stages) and one maintenance burn of the Coconino National Forest. Samples were analyzed for organic and elemental carbon, cations (sodium, potassium [K+], and ammonium [NH4+]), anions (nitrate [NO3-] and sulfate), and 48 elements (with atomic weights between sodium and lead). The PM2.5 contained high organic carbon levels (typically >90% by mass), commonly observed ions (K+, NH4+, and NO3-) and elements (K+, chlorine, sulfur, and silicon), as well as titanium and chromium. Flaming produced higher K+ and NH4+ levels than smoldering, and the elemental signature was more complex (20 versus 7 elements). Average organic carbon x 1.4 mass fractions (+/-standard deviation) were lower during flaming (92+/-14%) than during smoldering (124+/-24%). The maintenance (grassland) burn produced lower particle concentrations, lower NH4+ and NO3- levels, and higher K and chlorine levels than did the first-entry fires.

Utilização de implantes osseointegrados na reposição de dentes molares inferiores / The use of osseointegrated implants to replace lower molars

A última inovação da moderna Odontologia estética e a restauração de tecido duro e mole perdido pela recomposição da natualidade o mais próximo possível. Com o aumento da conscientização dos pacientes, do desenvolvimento das técnicas cirúrgica s e protéticas pela melhoria da proeficiêcia e conhecimento dos odontólogos, a função ideal e a estética podem ser obtidas até mesmo com restaurações protéticas suportadas por implantes, na região de molares. Fatores anatômicos, morfológicos e inadequadas quantidade e qualidade óssea, podem reduzir o grau de sucesso dos implantes dentários na parte posterior da mandíbula. Atualmente existem várias opções para reposição de dois dentes molares suportados por implantes: Implantes tipo Esthéticone-Brãnemark. Esta técnica é descrita, cirúrgica e proteticamente, em um caso cliníco.