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Importance: Radiation therapy to doses of 24 to 36 Gy is currently used to treat indolent B-cell lymphoma of the ocular adnexa; however, ocular adverse effects are common. Objective: To determine if a response-adapted radiation therapy strategy will result in excellent disease outcomes while reducing orbital morbidity. Design, Setting, and Participants: This single-institution, phase 2 prospective nonrandomized controlled trial of a response-adapted strategy involved 50 evaluable patients with stage I to IV indolent B-cell lymphoma of the ocular adnexa enrolled between July 2015 and January 2021. This treatment approach was also retrospectively evaluated with a separate 55-patient cohort treated between March 2013 and October 2021. All data were analyzed between November 2021 and December 2023. Interventions: Patients were treated with ultralow-dose radiation therapy to 4 Gy in 2 fractions and assessed for response at 3-month intervals. Patients with persistent orbital lymphoma were offered an additional 20 Gy in 10 fractions to complete the response-adapted treatment. Main Outcome and Measures: The primary end point was 2-year local orbital control within the irradiated field after response-adapted therapy. Secondary end points included overall survival and complete response rate. Results: The 50 prospective patients were a median (range) of 63 (29-88) years old, and 31 (62%) were female. Among the 50 patients, 32 (64%) had mucosa-associated lymphoid tissue lymphoma, 12 (24%) had follicular lymphoma, and 6 (12%) had unclassifiable low-grade B-cell lymphoma. Thirty-one patients (62%) had stage I disease, and 36 (72%) were newly diagnosed. At a median follow-up of 37.4 (95% CI, 33.7-52.5) months, the 2-year local control rate was 89.4% (95% CI, 81.0%-98.7%), and the 2-year overall survival rate was 98.0% (95% CI, 94.1%-100%); 45 patients (90.0%; 95% CI, 78.2%-96.7%) experienced a complete response to response-adapted radiation, including 44 patients with a complete response to ultralow-dose radiation and 1 patient with a complete response after an additional 20 Gy. No local recurrences were observed among patients with a complete response to response-adapted therapy. No grade 3 or higher toxic effects were observed. In a planned subset analysis of 22 patients with newly diagnosed, untreated stage I mucosa-associated lymphoid tissue lymphoma, the 2-year local control rate was 90.7% (95% CI, 79.2%-100%), and the 2-year freedom from distant relapse rate was 95.2% (95% CI, 86.6%-100%). Conclusion and Relevance: In this nonrandomized controlled trial, response-adapted ultralow-dose therapy for indolent orbital B-cell lymphoma resulted in reduced radiation exposure, negligible toxic effects, and excellent disease outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02494700.
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BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.
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Linfoma de Zona Marginal Tipo Células B , Dosagem Radioterapêutica , Neoplasias Gástricas , Humanos , Linfoma de Zona Marginal Tipo Células B/radioterapia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Gástricas/radioterapia , Neoplasias Gástricas/patologia , Idoso , Projetos Piloto , Adulto , Estudos Prospectivos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
The aims of this study were (i) to determine the effect of an algoclay-based decontaminant on the oral availability of three mycotoxins (deoxynivalenol; DON, ochratoxin A; OTA, and aflatoxin B1; AFB1) using an oral bolus model and (ii) to determine the effect of this decontaminant on the performance, intestinal morphology, liver oxidative stress, and metabolism, in broiler chickens fed a diet naturally contaminated with DON. In experiment 1, sixteen 27-day-old male chickens (approximately 1.6 kg body weight; BW) were fasted for 12 h and then given a bolus containing either the mycotoxins (0.5 mg DON/kg BW, 0.25 mg OTA/kg BW, and 2.0 mg AFB1/kg BW) alone (n = 8) or combined with the decontaminant (2.5 g decontaminant/kg feed; circa 240 mg/kg BW) (n = 8). Blood samples were taken between 0 h (before bolus administration) and 24 h post-administration for DON-3-sulphate, OTA, and AFB1 quantification in plasma. The algoclay decontaminant decreased the relative oral bioavailability of DON (39.9%), OTA (44.3%), and AFB1 (64.1%). In experiment 2, one-day-old male Ross broilers (n = 600) were divided into three treatments with ten replicates. Each replicate was a pen with 20 birds. The broiler chickens were fed a control diet with negligible levels of DON (0.19-0.25 mg/kg) or diets naturally contaminated with moderate levels of DON (2.60-2.91 mg/kg), either supplemented or not with an algoclay-based decontaminant (2 g/kg diet). Jejunum villus damage was observed on day 28, followed by villus shortening on d37 in broiler chickens fed the DON-contaminated diet. This negative effect was not observed when the DON-contaminated diet was supplemented with the algoclay-based decontaminant. On d37, the mRNA expression of glutathione synthetase was significantly increased in the liver of broiler chickens fed the DON-contaminated diet. However, its expression was similar to the control when the birds were fed the DON-contaminated diet supplemented with the algoclay-based decontaminant. In conclusion, the algoclay-based decontaminant reduced the systemic exposure of broiler chickens to DON, OTA, and AFB1 in a single oral bolus model. This can be attributed to the binding of the mycotoxins in the gastrointestinal tract. Moreover, dietary contamination with DON at levels between 2.69 and 2.91 mg/kg did not impair production performance but had a negative impact on broiler chicken intestinal morphology and the liver redox system. When the algoclay-based decontaminant was added to the diet, the harm caused by DON was no longer observed. This correlates with the results obtained in the toxicokinetic assay and can be attributed to a decreased absorption of DON.
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Aflatoxina B1 , Ração Animal , Galinhas , Contaminação de Alimentos , Fígado , Ocratoxinas , Estresse Oxidativo , Tricotecenos , Animais , Tricotecenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Masculino , Ocratoxinas/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Aflatoxina B1/toxicidade , Ração Animal/análise , Intestinos/efeitos dos fármacos , Intestinos/patologia , Toxicocinética , Dieta/veterinária , Silicatos de AlumínioRESUMO
Water kefir is a sparkling, slightly acidic fermented beverage made from sugar, water, and water kefir grains, which are a mixture of yeast and bacteria. These grains produce a variety of fermentation compounds such as lactic acid, acetaldehyde, acetoin, ethanol and carbon dioxide. In this study, a high-throughput sequencing technique was used to characterize the bacterial composition of the original water kefir from which potential probiotics were obtained. We studied the bacterial diversity of both water kefir grains and beverages. DNA was extracted from three replicate samples of both grains and beverages using the Powerlyzer Microbial Kit. The hypervariable V1-V2 region of the bacterial 16S ribosomal RNA gene was amplified to prepare six DNA libraries. Between 1.4M and 2.4M base-pairs were sequenced for the library. In total, 28721971 raw reads were obtained from all the samples. Estimated species richness was higher in kefir beverage samples compared to grain samples. Moreover, a higher level of microbial alpha diversity was observed in the beverage samples. Particularly, the predominant bacteria in beverages were Anaerocolumna and Ralstonia, while in grains Liquorilactobacillus dominated, with lower levels of Leuconostoc and Oenococcus. Although the bacterial diversity in kefir grains was low because only three genera were the most represented, all of them are LAB bacteria with the potential to serve as probiotics in the artificial feeding of bees.
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Bactérias , Kefir , Metagenômica , Probióticos , RNA Ribossômico 16S , Animais , Abelhas/microbiologia , Kefir/microbiologia , RNA Ribossômico 16S/genética , Metagenômica/métodos , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , DNA Bacteriano/análise , Biodiversidade , DNA Ribossômico/genética , Ração Animal/microbiologiaAssuntos
Imunoterapia Adotiva , Linfoma , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfoma/terapia , Linfócitos T , Rim , Antígenos CD19RESUMO
Managed populations of honey bees (Apis mellifera Linnaeus; Hymenoptera: Apidae) are regularly exposed to infectious diseases. Good hive management including the occasional application of antibiotics can help mitigate infectious outbreaks, but new beekeeping tools and techniques that bolster immunity and help control disease transmission are welcome. In this review, we focus on the applications of beneficial microbes for disease management as well as to support hive health and sustainability within the apicultural industry. We draw attention to the latest advances in probiotic approaches as well as the integration of fermented foods (such as water kefir) with disease-fighting properties that might ultimately be delivered to hives as an alternative or partial antidote to antibiotics. There is substantial evidence from in vitro laboratory studies that suggest beneficial microbes could be an effective method for improving disease resistance in honey bees. However, colony level evidence is lacking and there is urgent need for further validation via controlled field trials experimentally designed to test defined microbial compositions against specific diseases of interest.
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Criação de Abelhas , Abelhas , Fermentação , Microbioma Gastrointestinal , Probióticos , Animais , Antibacterianos/imunologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Criação de Abelhas/métodos , Abelhas/efeitos dos fármacos , Abelhas/imunologia , Abelhas/microbiologia , Fermentação/imunologia , Microbioma Gastrointestinal/imunologia , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared and characterized. An analysis by Fourier-transform infrared (FT-IR) spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. X-ray photoelectron spectroscopy suggested that the grafting reaction was viable. The morphology of the prepared nanocomposites studied by field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) showed significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revealed that the functionalized CNTs strongly affect the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of the prepared nanocomposites to inhibit the growth of the fungus Candida albicans and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was evaluated. A reduced antifungal and antibacterial capacity of the prepared nanocomposites was determined.
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Abstract We evaluated the microbial composition of water kefir grains and beverage overthe course of one year to determine whether the number and type of microorganisms changedover the time. Bacteria and yeast colonies with different morphologies were isolated fromwater kefir and their antimicrobial activity was evaluated against Paenibacillus larvae andAscosphaera apis. A chemical characterization of kefir was also carried out. Our results con-firmed that bacteria and yeasts were more numerous in kefir grains compared with those in thebeverage. The counts of microorganisms declined, although an important microbial community was still present in kefir after the long storage period. Eleven strains which inhibited bee pathogens were isolated from kefir. Genotypic results demonstrated that these isolates included Lentilactobacillus hilgardii, Lentilactobacillus buchneri and Saccharomyces cerevisiae. Thus, water kefir may be an innovative source of potential probiotic strains for bee nutrition in order to control honeybee diseases.
Resumen Evaluamos la composición microbiana del kéfir de agua durante un ano para determinar si la cantidad y el tipo de microorganismos cambiaban con el tiempo. Se aislaron colonias de bacterias y de levaduras con diferentes morfologías, y su actividad antimicrobiana se evaluó frente a Paenibacillus larvaey Ascosphaeraapis. También se realizó una caracterización química del kéfir. Nuestros resultados confirmaron que las bacterias y las levaduras eran más numerosas en los gránulos de kéfir en comparación con la parte líquida. Los recuentos de microorganismos disminuyeron, aunque una cantidad igualmente importante se encontró en el kéfir después de un año. Se aislaron del kéfir once cepas que inhibieron los mencionados patógenos de abejas. Los resultados genotípicos demostraron que estos aislamientos eran Lentilactobacillus hilgardii, Lentilactobacillus buchneri y Saccharomyces cerevisiae. Por lo tanto, el kéfir de agua podría ser una fuente innovadora de potenciales cepas probióticas para contribuir a la nutrición y sanidad de las abejas.
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We evaluated the microbial composition of water kefir grains and beverage over the course of one year to determine whether the number and type of microorganisms changed over the time. Bacteria and yeast colonies with different morphologies were isolated from water kefir and their antimicrobial activity was evaluated against Paenibacillus larvae and Ascosphaera apis. A chemical characterization of kefir was also carried out. Our results confirmed that bacteria and yeasts were more numerous in kefir grains compared with those in the beverage. The counts of microorganisms declined, although an important microbial community was still present in kefir after the long storage period. Eleven strains which inhibited bee pathogens were isolated from kefir. Genotypic results demonstrated that these isolates included Lentilactobacillus hilgardii, Lentilactobacillus buchneri and Saccharomyces cerevisiae. Thus, water kefir may be an innovative source of potential probiotic strains for bee nutrition in order to control honeybee diseases.
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Kefir , Probióticos , Abelhas , Animais , Kefir/microbiologia , Água , Bebidas/microbiologia , Bactérias , Saccharomyces cerevisiae , FermentaçãoRESUMO
INTRODUCTION: Patients undergoing cardiac surgery can experience significant thermal changes during the perioperative period and, for that reason, it is essential to monitor temperatures with adequate accuracy and precision during cardiopulmonary bypass (CPB). The primary aim of the current study was to measure the discrepancies between temperatures at different body sites during normothermic or mild hypothermic CPB. METHODS: 48 patients undergoing cardiac surgery participated in our study. Simultaneous temperatures were measured at nasopharynx, pulmonary artery, arterial outlet, venous inlet, forehead using a heat flux sensor, and urinary bladder at 5-min intervals throughout surgery. The Bland-Altman plot for repeated measures was used to assess concordance between methods. RESULTS: The duration of surgery was 360 min (interquartile range (IQR) 300-412), while the median cross-clamp time was 135 min (IQR 101-169). During the CPB time, the average difference between arterial outlet and nasopharyngeal temperature was -0.16°C (95% limits of agreement of ±0.93). The bias between arterial outlet and the venous inflow was 0.16°C and the 95% limits of agreement were -0.63 to 0.95°C. The Bland-Altman analysis showed an average difference between oxigenator arterial outlet and bladder probe of -0.62 (95% limits of agreement of ±1.3). The average difference between arterial outlet and Tcore™ temperatures was 0.08°C (95% limits of agreement of ±1.46). 25 patients (52.08%) presented nasopharyngeal temperatures higher than 37°C in the post-CPB period, but none of them exceeded 38°C. CONCLUSIONS: Perfusionists should be cautious when using the nasopharyngeal site as the only surrogate of brain temperature, even in normothermic cardiac surgery because the precision of measurements is not entirely adequate.
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Procedimentos Cirúrgicos Cardíacos , Hipotermia Induzida , Humanos , Temperatura Corporal , Reprodutibilidade dos Testes , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Artéria Pulmonar , Hipotermia Induzida/métodos , TemperaturaRESUMO
Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant genetic disease characterized by development of schwannomas on the VIIIth (vestibular) cranial nerves. Bromodomain and extra-terminal domain (BET) proteins regulate gene transcription and their activity is required in a variety of cancers including malignant peripheral nerve sheath tumors. The use of BET inhibitors as a therapeutic option to treat NF2 schwannomas has not been explored and is the focus of this study. Methods: A panel of normal and NF2-null Schwann and schwannoma cell lines were used to characterize the impact of the BET inhibitor JQ1 in vitro and in vivo. The mechanism of action was explored by chromatin immunoprecipitation of the BET BRD4, phospho-kinase arrays and immunohistochemistry (IHC) of BRD4 in vestibular schwannomas. Results: JQ1 inhibited proliferation of NF2-null schwannoma and Schwann cell lines in vitro and in vivo. Further, loss of NF2 by CRISPR deletion or siRNA knockdown increased sensitivity of cells to JQ1. Loss of function experiments identified BRD4, and to a lesser extent BRD2, as BET family members mediating the majority of JQ1 effects. IHC demonstrated elevated levels of BRD4 protein in human vestibular schwannomas. Analysis of signaling pathways effected by JQ1 treatment suggests that the effects of JQ1 treatment are mediated, at least in part, via inhibition of PI3K/Akt signaling. Conclusions: NF2-deficient Schwann and schwannoma cells are sensitive to BET inhibition, primarily mediated by BRD4, which is overexpressed in human vestibular schwannomas. Our results suggest BRD4 regulates PI3K signaling and likely impedes NF2 schwannoma growth via this inhibition. These findings implicate BET inhibition as a therapeutic option for NF2-deficient schwannomas.
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A detailed study of lead halide-layered perovskites with general formula A2PbX4 (where A is cyclohexylammonium (CHA) or cyclopentylammonium (CPA) cation and X is Cl- or Br- anion) is presented. Using variable temperature synchrotron X-ray powder diffraction, we observe that these compounds exhibit diverse crystal structures above room temperature. Very interestingly, we report some unconventional thermomechanical responses such as uniaxial negative thermal expansion and colossal positive thermal expansion in a perpendicular direction. For the polymorphs of (CHA)2PbBr4, the volumetric thermal expansion coefficient is among the highest reported for any extended inorganic crystalline solid, reaching 480 MK-1. The phase transitions are confirmed by calorimetry and dielectric measurements, where the dielectric versus temperature curves show anomalies related with the order-disorder phase transitions. In addition, these compounds exhibit a broad photoluminescence (PL) emission with a large Stokes shift, which is related with an exciton PL emission.
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Purpose: Therapeutic improvements for Hodgkin's Lymphoma (HL) has resulted in excellent survival outcomes. Thus, patients are increasing susceptible to developing secondary malignancy (SM) a feared iatrogenic complication. Materials & Methods: We evaluated the SM risk in a cohort of patients with HL treated over a 50-year period. In total, 1653 patients were treated for HL from 1956 to 2009 at a tertiary-cancer-center. A cumulative incidence function was used to quantify SM risk and the Fine and Gray competing risk model was used to identify disease and treatment related correlates. Results: Two-hundred-ninety patients (19%) developed SMs. Paradoxically, SM risk was higher in the modern era with 20-year cumulative incidence rates of 11.1%, 11.9%, 17% and 21.8%, for patients treated <1970, 1971-1986, 1986-1995 and 1996-2009, respectively. We hypothesized that the disproportionately high rate of early deaths in the early era may skew the assessment of SM risks, a much-delayed event. When the analysis was restricted to patients with early-stage favorable HL treated >1980, we found a reversal of the trend, especially on the risk of solid tumor, with a hazard ratio of 0.57 (p = 0.0651) in patients treated after 1996. Conclusion: Our findings highlight the limitations of comparing the risk of a late event between groups with disparate rates of early deaths, despite the use of a competing risk model. When partially corrected for, patients treated in the more recent time period experienced a lower solid tumor risk.
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The present work is related to the treatment of crushed waste of printed circuit boards (WPCBs) from electrical and electronic devices (WEEE), carrying out the recovery of copper in solution. In the first stage, the studied material was characterized by AAS, SEM-EDS, and XRD. The results revealed significantly high amounts of copper (744.42 mg/g), compared with the rest of the metals present in the sample, mainly iron and zinc. In the second stage of the work, alkali dynamic leaching experiments were carried out in the S2O3−2− O2 medium, evaluating important kinetic variables in order to verify the controlling step of the system and adjust the data to a kinetic model. According to the results obtained from the various experimental tests executed, it was found that in the studied system of S2O3−2− O2, the leaching of copper was preferably adjusted to the model of spherical particles with a shrinking core finding a mixed chemical−diffusive control, with values of Ea = 25.78 kJ/mol and n = 0.22 (for the leaching reagent), indicating that the reaction was controlled by the oxygen transport to the solid−liquid interface and also by the chemical reaction in the surface of particles, obtaining up to 99.82% copper in solution.
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Limited data exist regarding the outcome of patients with follicular lymphoma (FL) who relapse or progress after frontline lenalidomide and rituximab (R2). Moreover, mechanisms of resistance to R2 in FL remain unclear, with increased protumoral macrophages suspected as a major contributory culprit to this phenomenon. This retrospective study analyzed the outcome of patients with advanced-stage FL grade 1 to 3A who relapsed or progressed after frontline R2. A multiplex immunofluorescence macrophage panel, including CD47, CD14, CD68, CD115 (also known as colony-stimulating factor 1 receptor [CSF1R]), CD163, CD172a (also known as signal regulatory protein α [SIRPα]), and CD274 (also known as programmed cell death-ligand 1 [PDL1]), was used to stain tissue biopsy specimens collected before initiation of R2 and at the time of progression. Among 156 patients with advanced-stage FL treated with frontline R2, 33 (21%) relapsed or progressed and required second-line therapy, after a median of 33 months (range, 1-122 months). Second-line therapy was chemoimmunotherapy in 16 (48%) patients and other therapy in 17 (52%). The overall response rate was 78%, and complete response rate was 72%. Median progression-free survival was significantly longer in patients who received chemoimmunotherapy compared with other therapy (99 vs 25 months; P = .004). Three macrophage populations were significantly increased in tissue samples collected at progression compared with before frontline treatment: CD68+CD115+ (P = .02), CD68+CD115+CD172a+ (P = .02), and CD68+CD163+CD172a+ (P = .01). Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. Therapies targeting specific macrophage populations may yield novel approaches for improving outcomes with frontline R2.
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Linfoma Folicular , Humanos , Lenalidomida/uso terapêutico , Macrófagos/patologia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Rituximab/uso terapêuticoRESUMO
Ionic liquids (ILs) and deep eutectic solvents (DESs) are the two most widely used neoteric solvents. Recently, our group described how the simple addition of acetic acid (AcOH) to 1-Ethyl-3-methylimidazolium chloride (EMIMCl) could promote the transition from the original IL to an eutectic mixture of EMIMCl and AcOH. Herein, we studied how cellulose regeneration and EMIMCl recovery from EMIMCl solutions of cellulose could be benefited by the significant differences existing between EMIMCl- and EMIMCl·AcOH-based mixtures and the easy switching from one to the other. Finally, we also demonstrated that the transition could also be accomplished by addition of acetic anhydride and water so that the process could be eventually useful for the achievement of highly acetylated cellulose.
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This study evaluated the effect of an algoclay-based mycotoxin decontaminant on the levels of ZEN, DON, and their derivatives in the colostrum, milk, and serum of sows, as well as in the serum of weaned piglets after maternal mycotoxin exposure during the last week of gestation and during lactation of sows (26 days). For this, sows (n = 5) were fed diets artificially contaminated with 100 (LoZEN) or 300 (HiZEN) ppb ZEN, with or without an algoclay-based mycotoxin decontaminant in the highly contaminated diet. All diets contained 250 ppb deoxynivalenol (DON). Dietary treatments did not affect the performance of the sows and piglets. Only α-ZEL was significantly increased in the colostrum of sows fed the HiZEN diet, and this increase was even higher in the colostrum of the sows fed the HiZEN diet supplemented with the test decontaminant. However, no differences in milk mycotoxin levels were observed at weaning. The highest levels of ZEN, α-ZEL, and ß-ZEL were observed in the serum of sows fed the HiZEN diet. When the HiZEN diet was supplemented with the tested algoclay-based mycotoxin decontaminant the levels of ZEN and its metabolites were significantly decreased in the serum of sows. Although all sows were fed the same levels of DON, the serum level of de-epoxy-DON was increased only in the serum of piglets from the sows fed a diet with the non-supplemented HiZEN diet. In conclusion, the tested algoclay-based mycotoxin decontaminant can decrease the levels of ZEN and its metabolites in the serum of sows and the level of de-DON in the serum of piglets.
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The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , HumanosRESUMO
OBJECTIVE: To determine nickel levels and their impact on protein carbonylation in gum samples from patients with gingival overgrowth by orthodontic treatment. DESIGN: A retrospective observational study with 33 patients divided into three groups. Group 1 patients with gingival overgrowth by orthodontic appliances; group 2 patients without gingival overgrowth but with a history of orthodontic treatment; group 3 patients without overgrowth and history of orthodontic appliances. Nickel level in gingiva samples was measured by atomic absorption while protein carbonylation was determined by Western Blot. Furthermore, three proteins were identified in carbonylated protein bands by mass spectrometry. RESULTS: Statistically significant differences (p < 0,05) in tissue nickel levels among groups were established (nickel levels group 1: 1.33 ± 1.52; group 2: 0.33 ± 0.44; group 3: 0.20 ± 0.22 µg Ni/g tissue). Protein carbonylation was higher in patients with gingival enlargement (group 1) and history of appliance use (group 2) than controls (group 3). It was observed that band A of the Western blots presented the highest intensity (Rf 0.23) with an average intensity of 4.133.830 ± 1.958.569 for group 1; 4.420.146 ± 1.594.679 for group 2 and 2.110. 727 ± 1.640.721 for group 3. Also, the proteins Teneurin-4, Bromodomain adjacent to zinc finger domain protein 2B, Lysine-specific demethylase 5B, and Serum albumin, were identified from oxidized bands. CONCLUSIONS: The gum of patients with gingival overgrowth by orthodontic appliances contains higher nickel residues and carbonylation of its proteins.