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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with historically poor outcomes and no worldwide consensus treatment approach. Unique among most hematologic malignancies for its frequent cutaneous involvement, BPDCN can also invade other extramedullary compartments, including the central nervous system. Generally affecting older adults, many patients are unfit to receive intensive chemotherapy, and although hematopoietic stem cell transplantation is preferred for younger, fit individuals, not all are eligible. One recent therapeutic breakthrough is that all BPDCNs express CD123 (IL3Rα) and that this accessible surface marker can be pharmacologically targeted. The first-in-class agent for BPDCN, tagraxofusp, which targets CD123, was approved in December 2018 in the United States for patients with BPDCN aged ≥2 years. Despite favorable response rates in the frontline setting, many patients still relapse in the setting of monotherapy, and outcomes in patients with relapsed/refractory BPDCN remain dismal. Therefore, novel approaches targeting both CD123 and other targets are actively being investigated. To begin to formally address the state of the field, we formed a new collaborative initiative, the North American BPDCN Consortium (NABC). This group of experts, which includes a multidisciplinary panel of hematologists/oncologists, hematopoietic stem cell transplant physicians, pathologists, dermatologists, and pediatric oncologists, was tasked with defining the current standard of care in the field and identifying the most important research questions and future directions in BPDCN. The position findings of the NABC's inaugural meetings are presented herein.
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Neoplasias Hematológicas , Transtornos Mieloproliferativos , Neoplasias Cutâneas , Criança , Humanos , Idoso , Padrão de Cuidado , Subunidade alfa de Receptor de Interleucina-3 , Células Dendríticas/patologia , Recidiva Local de Neoplasia/patologia , Transtornos Mieloproliferativos/patologia , Neoplasias Hematológicas/patologia , Neoplasias Cutâneas/patologia , Doença Aguda , América do NorteRESUMO
Currently, analysis of interim PET (iPET) according to the Deauville score (DS) is the most important predictive factor in Hodgkin lymphoma (HL); however, there is room for improvement in its prognostic power. This study aimed to evaluate the prognostic value of quantitative PET analysis (maximum standard uptake value [SUVmax], total metabolic tumor volume [TMTV] and total lesion glicolysis [TLG]) at baseline (PET0) and iPET in a retrospective cohort of newly diagnosed classical HL. For positive iPET (+ iPET), the reduction of quantitative parameters in relation to PET0 (ΔSUVmax, ΔTMTV and ΔTLG) was calculated. Between 2011 and 2017, 234 patients treated with ABVD were analyzed. Median age was 30 years-old, 59% had advanced stage disease, 57% a bulky mass and 25% a + iPET (DS 4-5). At baseline, high TLG was associated with an increased cumulative incidence of failure (CIF) (p = 0.032) while neither SUVmax, TMTV or TLG were associated with overall survival (OS) or progression-free survival (PFS). In multivariate analysis, only iPET was associated with CIF (p < 0.001). Among ΔSUVmax, ΔTMTV and ΔTLG, only a ΔSUVmax ≥ 68.8 was significant for PFS (HR: 0.31, CI95%: 0.11-0.86, p = 0.024). A subset of patients with improved PFS amongst + iPET was identified by the quantitative (ΔSUVmax ≥ 68.8%) analysis. In this real-world Brazilian cohort, with prevalent high-risk patients, quantitative analysis of PET0 did not demonstrate to be prognostic, while a dynamic approach incorporating the ΔSUVmax to + iPET succeeded in refining a subset with better prognosis. These findings warrant validation in larger series and indicate that not all patients with + iPET might need treatment intensification.
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Doença de Hodgkin , Humanos , Adulto , Estudos Retrospectivos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluordesoxiglucose F18 , Bleomicina , Dacarbazina , Doxorrubicina , Vimblastina , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de PósitronsRESUMO
As a highly successful introduced species, house sparrows (Passer domesticus) respond rapidly to their new habitats, generating phenotypic patterns across their introduced range that resemble variation in native regions. Epigenetic mechanisms likely facilitate the success of introduced house sparrows by aiding particular individuals to adjust their phenotypes plastically to novel conditions. Our objective here was to investigate patterns of DNA methylation among populations of house sparrows at a broad geographic scale that included different introduction histories: invading, established, and native. We defined the invading category as the locations with introductions less than 70 years ago and the established category as the locations with greater than 70 years since introduction. We screened DNA methylation among individuals (nâ =â 45) by epiRADseq, expecting that variation in DNA methylation among individuals from invading populations would be higher when compared with individuals from established and native populations. Invading house sparrows had the highest variance in DNA methylation of all three groups, but established house sparrows also had higher variance than native ones. The highest number of differently methylated regions were detected between invading and native populations of house sparrow. Additionally, DNA methylation was negatively correlated to time-since introduction, which further suggests that DNA methylation had a role in the successful colonization's of house sparrows.
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Metilação de DNA , Pardais , Humanos , Animais , Pardais/genética , Epigênese Genética , EcossistemaRESUMO
BACKGROUND: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical-pathological features. METHODS: The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. RESULTS: Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6-5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively). CONCLUSION: PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.
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Antígeno B7-H1 , Instabilidade de Microssatélites , Neoplasias Primárias Desconhecidas , Humanos , Neoplasias Primárias Desconhecidas/genética , Neoplasias Primárias Desconhecidas/patologia , Antígeno B7-H1/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Prognóstico , Microambiente Tumoral , Imuno-HistoquímicaRESUMO
BACKGROUND: The L5-S1 interlaminar access described in 2006 by Ruetten et al. represented a paradigm shift and a new perspective on endoscopic spinal approaches. Since then, the spinal community has shown that both the traditional ipsilateral and novel contralateral interlaminar approaches to the L5-S1 foramen are good alternatives to transforaminal access. This study aimed to provide a technical description and brief case series analysis of a new endoscopic foraminal and extraforaminal approach for pathologies at the lumbar L5-S1 level using a new ipsilateral interlaminar approach. METHODS: Thirty patients with degenerative stenotic conditions at the L5-S1 disc level underwent the modified interlaminar approach. The surgical time, blood loss, occurrence of complications, and clinical outcomes were recorded. The data were compiled in Excel and analyzed using R software version 4.2. All continuous variables are presented as the mean, median, minimum, and maximal ranges. For categorical variables, data are described as counts and percentages. RESULTS: Thirty patients were included in the study. The cohort showed significant improvements in all quality-of-life scores (ODI, visual analog scale of back pain, and visual analog scale of leg pain). Five cases of postoperative numbness and three cases of postoperative dysesthesia have been reported. No case of durotomy or leg weakness has been reported. CONCLUSIONS: The fundamental change proposed by this procedure, the new ipsilateral approach, presents potential advantages to surgeons by overcoming anatomical challenges at the L5-S1 level and by providing surgeon-friendly visualization and access. This approach allows for extensive foraminal and extraforaminal decompression, including the removal of hernias and osteophytosis, without causing neural retraction of the L5-S1 roots while maintaining the stability of the operated level.
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Descompressão Cirúrgica , Vértebras Lombares , Humanos , Feminino , Masculino , Descompressão Cirúrgica/métodos , Pessoa de Meia-Idade , Vértebras Lombares/cirurgia , Idoso , Adulto , Sacro/cirurgia , Endoscopia/métodos , Estenose Espinal/cirurgia , Resultado do Tratamento , Neuroendoscopia/métodosRESUMO
This study evaluated the use of acerola (Malpighia glabra L., CACE), cashew (Anacardium occidentale L., CCAS), and guava (Psidium guayaba L., CGUA) fruit processing coproducts as substrates to promote the growth, metabolite production, and maintenance of the viability/metabolic activity of the probiotics Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 during cultivation, freeze-drying, storage, and exposure to simulated gastrointestinal digestion. Probiotic lactobacilli presented high viable counts (≥8.8 log colony-forming units (CFU)/mL) and a short lag phase during 24 h of cultivation in CACE, CCAS, and CGUA. Cultivation of probiotic lactobacilli in fruit coproducts promoted sugar consumption, medium acidification, and production of organic acids over time, besides increasing the of several phenolic compounds and antioxidant activity. Probiotic lactobacilli cultivated in fruit coproducts had increased survival percentages after freeze-drying and during 120 days of refrigerated storage. Moreover, probiotic lactobacilli cultivated and freeze-dried in fruit coproducts had larger subpopulations of live and metabolically active cells when exposed to simulated gastrointestinal digestion. The results showed that fruit coproducts not only improved the growth and helped to maintain the viability and metabolic activity of probiotic strains but also enriched the final fermented products with bioactive compounds, being an innovative circular strategy for producing high-quality probiotic cultures.
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Frutas , Probióticos , Probióticos/metabolismo , Frutas/microbiologia , Lactobacillus acidophilus/crescimento & desenvolvimento , Lactobacillus acidophilus/metabolismo , Lactobacillus acidophilus/fisiologia , Anacardium/microbiologia , Anacardium/crescimento & desenvolvimento , Psidium/crescimento & desenvolvimento , Psidium/microbiologia , Malpighiaceae/crescimento & desenvolvimento , Malpighiaceae/microbiologia , Liofilização , Viabilidade Microbiana , Lacticaseibacillus paracasei/crescimento & desenvolvimento , Lacticaseibacillus paracasei/metabolismo , Lacticaseibacillus paracasei/fisiologia , Fermentação , Manipulação de Alimentos/métodosRESUMO
BACKGROUND: Extract of ciriguela residue was microencapsulated by spray-drying and freeze-drying using maltodextrin (M), gum arabic (GA) and their mixture (50% M; 50% GA on dry basis) as encapsulating agents. Total phenolic compounds (TPC), antioxidant activity, physicochemical properties, profile of phenolic compounds by HPLC with diode-array detection and storage stability were evaluated. RESULTS: TPC content of powders ranged from 306.9 to 451.2 mg gallic acid equivalent g-1 dry powder. The spray-dried powder prepared using GA as encapsulating agent had higher TPC content and antioxidant activity, whereas the freeze-dried powder had lower moisture and water activity. Spray-dried microcapsules had spherical shape, whereas freeze-dried products had irregular structures. The profile of phenolic compounds identified in samples was similar, with rutin (342.59 and 72.92 µg g-1 ) and quercetin (181.02 and 43.24 µg g-1 ) being the major compounds in liquid and freeze-dried extracts, respectively, whereas myricetin (97.41 µg g-1 ) was predominant in spray-dried ones. Storage stability tests carried out for 45 days at 7 or 25 °C revealed no statistically significant difference in TPC. CONCLUSION: Ciriguela residue can be considered a source of TPC and used as ingredient with good antioxidant activity in the food industry. © 2023 Society of Chemical Industry.
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Antioxidantes , Fenóis , Antioxidantes/química , Pós/química , Fenóis/química , Liofilização , Extratos Vegetais/química , Goma Arábica/químicaRESUMO
Retrieving information from memory enhances long-term retention. In this manuscript, we describe the dual-memory framework, which makes interval-scale predictions of the magnitude of this retrieval practice effect. After outlining the framework, we use data from our laboratory-both at the group level and at the distribution level-to fit the equations from the dual-memory framework. Overall, we successfully fitted the model predictions to the observed average data. In addition, we compared the predicted and the observed distributions of performance in the retrieval practice condition. More importantly, we introduce a useful approach to simulate empirical scenarios and test the relationship between individual-difference variables and the retrieval practice effect. We illustrate the application of this approach using data from a study that measured fluid intelligence. Future studies may benefit from contrasting different strength-based frameworks.
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The color of grape juice is an important acceptance attribute by consumers, but it suffers losses during storage. The use of commercial antioxidants has limitations because the concept of a "100% natural drink" of Brazilian legislation. This work characterized Brazilian grape seeds, and the cultivar extract with the greatest potential was encapsulated in arabic-gum (encapsulated extract-EE) to evaluate the color stabilizing capacity. The EE used in the grape juice was compared with the commercial antioxidants sulphite and enological tannin during storage (150 days). The BRS Magna and BRS Violeta grape seeds had the highest phenolic content, and the EE showed high catechin (4108 mg/kg), epicatechin (1161 mg/kg) and procyanidin-B2 (905 mg/kg) values. Sulfite was found to be the best color stabilizer. The use of EE (0.5 g/L) in grape juice improved color stability and anthocyanin stability. It was demonstrated that encapsulated grape seed extract has color stabilizing potential and that Brazilian grape seeds are a raw material of high technological value. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05956-8.
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AIMS: To evaluate the phytochemical composition and effects of the baru peel and pulp (BPP) and the partially defatted baru nut (DBN) on the growth and metabolism of probiotics. METHODS AND RESULTS: The proximate composition, including dietary fibers, and polyphenol profile were determined in the BPP and DBN, and the prebiotic activity was evaluated on the growth and metabolism of the Lactobacillus and Bifidobacterium strains. BPP and DBN have a high content of insoluble fibers and phenolic compounds, mainly flavonoids and phenolic acids. Moreover, DBN stands out for its high content of proteins and lipids. BPP and DBN stimulated the growth and metabolism of Bifidobacterium animalis subsp. lactis BB-12, Lactobacillus acidophilus LA-05, and Lacticaseibacillus casei L-26. CONCLUSIONS: Baru by-products have potential prebiotic properties to be confirmed in preclinical and clinical studies, and to be explored as an ingredient in new health-promoting foods. IMPACT STATEMENT: Agro-industrial baru wastes, the peel plus pulp and the partially defatted nut, are sources of health-promoting compounds and stimulate the growth and metabolism of probiotics, indicating prebiotic properties.
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Bifidobacterium animalis , Dipteryx , Probióticos , Bifidobacterium , Fibras na Dieta , Resíduos IndustriaisRESUMO
This study evaluated the effects of a phenolic-rich extract from jabuticaba [Myrciaria jaboticaba (Vell.) Berg] depulping waste (PEJ) on the survival, antibiotic susceptibility, virulence, and cellular functions of various enterotoxigenic Escherichia coli (ETEC) strains. The minimum inhibitory concentration of PEJ against the five tested ETEC strains was 125 mg mL-1. PEJ at 125 and 250 mg mL-1 caused reductions in viable cell counts of ≥ 3 and ≥ 5 log CFU mL-1 in ETEC over 24 h, respectively. PEJ at subinhibitory concentrations (31.25 and 62.5 mg mL-1) reduced the viable cell counts of ETEC when exposed to in vitro gastrointestinal conditions, besides decreasing the biofilm formation, cell surface hydrophobicity, mucin adhesion, and swimming and swarming motility. PEJ (31.25 and 62.5 mg mL-1) increased the susceptibility of the tested ETEC strains to various clinically relevant antibiotics. The exposure to PEJ (62.5 and 125 mg mL-1) impaired the membrane permeability and enzymatic and efflux pump activities in ETEC cells. PEJ effectively reduces survival, increases antibiotic susceptibility, and attenuates virulence in ETEC. These effects could be linked to a PEJ multi-target action disturbing various cellular functions in ETEC cells. PEJ could be a candidate for developing innovative solutions to prevent and treat ETEC infections.
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Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Humanos , Infecções por Escherichia coli/tratamento farmacológico , Antibacterianos/farmacologia , Virulência , Fatores de Virulência/metabolismo , DiarreiaRESUMO
Indicator species are frequently used to monitor restoration areas. However, species of conservation concern are usually absent in highly fragmented landscapes, making the selection of indicator species a challenging task. Here, we select indicator species of birds and mammals to be used for the evaluation of restoration sites in a highly fragmented landscape, the Capivara-Taquaruçu Dams region located in north Paraná, Brazil. By using the Index of Biotic Integrity (IBI), we show that the Capivara-Taquaruçu Dams landscape has low IBI values and bird richness when compared with two other landscapes in the north of Paraná. Therefore, we used the Individual Indicate Value to identify birds and mammals associated with forest fragments in the Capivara-Taquaruçu Dams landscape. Six bird and four mammal species were selected as indicators of forest fragments, none of which were of conservation concern. However, monitoring of these species could help evaluate the recovery of restoration sites in the Capivara-Taquaruçu Dams region. Lastly, several species of birds and mammals were frequently recorded in the restoration sites, including vulnerable species such as the lowland tapir (Tapirus terrestris). This is indicative that restoration sites can be important habitats in highly fragmented landscapes despite the loss of biodiversity.
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Ecossistema , Florestas , Animais , Biodiversidade , Mamíferos , Aves , Conservação dos Recursos NaturaisRESUMO
Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized. Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants. Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research. Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples. Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models. Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001). Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasia Residual , Análise de Sequência de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Neoplasia Residual/sangue , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Proteínas Nucleares/genética , Cuidados Pré-Operatórios , Estudos Retrospectivos , Recidiva , Análise de SobrevidaRESUMO
The combination of fruit pulps from different species, in addition to multiplying the offer of flavors, aromas and textures, favors the nutritional spectrum and the diversity of bioactive principles. The objective was to evaluate and compare the physicochemical characteristics, bioactive compounds, profile of phenolic compounds and in vitro antioxidant activity of pulps of three species of tropical red fruits (acerola, guava and pitanga) and of the blend produced from the combination. The pulps showed significant values of bioactive compounds, with emphasis on acerola, which had the highest levels in all parameters, except for lycopene, with the highest content in pitanga pulp. Nineteen phenolic compounds were identified, being phenolic acids, flavanols, anthocyanin and stilbene; of these, eighteen were quantified in acerola, nine in guava, twelve in pitanga and fourteen in the blend. The blend combined positive characteristics conferred by the individual pulps, with low pH favorable for conservation, high levels of total soluble solids and sugars, greater diversity of phenolic compounds and antioxidant activity close to that of acerola pulp. Pearson's correlation between antioxidant activity and ascorbic acid content, total phenolic compounds, flavonoids, anthocyanins and carotenoids for the samples were positive, indicating their use as a source of bioactive compounds.
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Eugenia , Psidium , Antioxidantes/química , Frutas/química , Antocianinas/análise , Ácido Ascórbico/análise , Fenóis/química , Psidium/químicaRESUMO
Construction environment is composed of various substances classified as carcinogens. Thus, workers exposed in this environment can be susceptible to genomic instability that can be evaluated by absolute telomere length (TL). In this work, we evaluated TL in construction workers compared to a non-exposed group performed by qPCR assay. The TL was evaluated in 59 men exposed to the construction environment (10 years of exposure) and 49 men non-exposed. Our data showed that individuals exposed to the construction environment exhibited a significantly lower TL in relation to non-exposed group (p = 0.009). Also, on the multiple linear regression model, we observed that TL was significantly influenced by the construction environment exposure (p ≤ 0.001). Additionally, the arsenic exposure is associated to a shortening telomere (p ≤ 0.001), and the lead exposure caused an increase in TL (p ≤ 0.001). Thus, our findings suggest a modulation in TL by construction environment exposure, mainly by arsenic and lead exposure.
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Arsênio , Masculino , Humanos , Arsênio/toxicidade , Chumbo/toxicidade , Exposição Ambiental , Linfócitos , TelômeroRESUMO
The aim of this study was to evaluate the phenolic composition, sugars, and organic acids by HPLC-DAD/RID, and the antioxidant capacity of 100% commercial 'Syrah' and 'Tempranillo' red wines from the San Francisco Valley-SFV wineries, and to compare them with commercial monovarietal wines of the same cultivars from countries such as South Africa, Spain, Chile, and Australia. In total, 25 phenolic compounds were quantified and classified into chemical groups in all wines (phenolics acids, flavanones, flavan-3-ols, flavonols, anthocyanins, and stilbenes). Among these, catechin, procyanidins B1 and B2, lactic acid, and antioxidant capacity were highlighted as the markers responsible for the typification of SFV wines when compared to wines from temperate regions. The data reported here contribute to the knowledge of the potential for producing quality wines in tropical climate regions. The wines of cultivars 'Syrah' and 'Tempranillo' are consolidated among the wineries in the SFV region, Brazil, due to their excellent adaptation to the semi-arid tropical climate. The SFV recently applied for a wine geographical indication as its wines are young with tropical climate typicity. This study shows that it is possible to differentiate SFV Syrah and Tempranillo wines from other world regions by HPLC molecular profile using chemometric techniques. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05739-7.
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It is not known whether obesity has a differential effect on allogeneic haematopoietic cell transplantation outcomes with alternative donor types. We report the results of a retrospective registry study examining the effect of obesity [body mass index (BMI) > 30] on outcomes with alternative donors (haploidentical related donor with two or more mismatches and receiving post-transplant cyclophosphamide [haplo] and cord blood (CBU)] versus matched unrelated donor (MUD). Adult patients receiving haematopoietic cell transplantation for haematologic malignancy (2013-2017) (N = 16 182) using MUD (n = 11 801), haplo (n = 2894) and CBU (n = 1487) were included. The primary outcome was non-relapse mortality (NRM). The analysis demonstrated a significant, non-linear interaction between pretransplant BMI and the three donor groups for NRM: NRM risk was significantly higher with CBU compared to haplo at BMI 25-30 [hazard ratio (HR) 1.66-1.71, p < 0.05] and MUD transplants at a BMI of 25-45 (HR, 1.61-3.47, p < 0.05). The results demonstrated that NRM and survival outcomes are worse in overweight and obese transplant recipients (BMI ≥ 25) with one alternative donor type over MUD, although obesity does not appear to confer a uniform differential mortality risk with one donor type over the other. BMI may serve as a criterion for selecting a donor among the three (MUD, haplo and CBU) options, if matched sibling donor is not available.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Índice de Massa Corporal , Seleção do Doador , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Recidiva Local de Neoplasia , Obesidade , Estudos Retrospectivos , Doadores não RelacionadosRESUMO
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-c) is associated with severe cardiovascular impairment and eventually death. Pathophysiological mechanisms involved in myocardial injury were scarcely investigated, and cardiovascular outcomes are uncertain. Autopsy studies suggested that microvascular dysfunction may be relevant to LV impairment. OBJECTIVE: We aimed to evaluate segmental LV longitudinal strain by 2DST echocardiography and myocardial flow reserve (MFR) by 13 N-ammonia PET-CT, in six surviving MIS-c patients. METHODS: Each patient generated 34 LV segments for combined 2DST and MRF analysis. MFR was considered abnormal when <2, borderline when between 2 and 2.5 and normal when >2.5. RESULTS: From July 2020 to February 2021, six patients were admitted with MIS-c: three males, aged 9.3 (6.6-15.7) years. Time from admission to the follow-up visit was 6.05 (2-10.3) months. Although all patients were asymptomatic and LV EF was ≥55%, 43/102 (42.1%) LV segments showed MFR <2.5. There was a modest positive correlation between segmental peak systolic longitudinal strain and MFR: r = .36, p = .03 for basal segments; r = .41, p = .022 for mid segments; r = .42, p = .021 for apical segments. Median peak systolic longitudinal strain was different among MRF categories: 18% (12%-24%) for abnormal, 18.5% (11%-35%) for borderline, and 21% (12%-32%) for normal MFR (p = .006). CONCLUSION: We provided preliminary evidence that surviving MIS-c patients may present subclinical impairment of myocardial microcirculation. Segmental cardiac strain assessment 2DST seems useful for MIS-c cardiovascular follow-up, given its good correlation with 13 N-ammonia PET-CT derived MFR.
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Disfunção Ventricular Esquerda , Amônia , Criança , Ecocardiografia/métodos , Humanos , Masculino , Microcirculação , Miocárdio , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Background Chimeric antigen receptor (CAR) T-cell immunotherapy is increasingly used for refractory lymphoma but may lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Imaging may assist in clinical management. Associations between CRS or ICANS grade and imaging findings remain not fully established. Purpose To determine associations between imaging findings and clinical grade of CRS or ICANS, evaluate response patterns, and assess imaging use following CAR T-cell treatment. Materials and Methods Patients with refractory B-cell lymphoma who received CAR T-cell infusion between 2018 and 2020 at a single center were analyzed retrospectively. Clinical CRS or ICANS toxicity grade was assessed using American Society for Transplantation and Cellular Therapy, or ASTCT, consensus grading. Thoracic and head images (radiographs, CT scans, MRI scans) were evaluated. Associations between imaging findings and clinical CRS or ICANS grade were analyzed. Wilcoxon signed-rank and χ2 tests were used to assess associations between thoracic imaging findings, clinical CRS toxicity grade, and imaging-based response. Response to therapy was evaluated according to Deauville five-point scale criteria. Results A total of 38 patients (mean age ± standard deviation, 59 years ± 10; 23 men) who received CAR T-cell infusion were included. Of these, 24 (63% [95% CI: 48, 79]) and 11 (29% [95% CI: 14, 44]) experienced clinical grade 1 or higher CRS and ICANS, respectively. Patients with grade 2 or higher CRS were more likely to have thoracic images with abnormal findings (10 of 14 patients [71%; 95% CI: 47, 96] vs five of 24 patients [21%; 95% CI: 4, 37]; P = .002) and more likely to have imaging evidence of pleural effusions (five of 14 [36%; 95% CI: 10, 62] vs two of 24 [8.3%; 95% CI: 0, 20]; P = .04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; P = .048). Positive imaging findings were identified in three of seven patients (43%) with grade 2 or higher ICANS who underwent neuroimaging. The best treatment response included 20 of 36 patients (56% [95% CI: 39, 72]) with complete response, seven of 36 (19% [95% CI: 6, 33]) with partial response, one of 36 (2.8% [95% CI: 0, 8]) with stable disease, and eight of 36 (22% [95% CI: 8, 36]) with progressive disease. Conclusion Thoracic imaging findings, including pleural effusions and atelectasis, correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. CAR T-cell therapy yielded high response rates. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Langer in this issue.
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Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Síndrome da Liberação de Citocina/etiologia , Imunoterapia Adotiva/efeitos adversos , Linfoma Difuso de Grandes Células B/terapia , Síndromes Neurotóxicas/etiologia , Receptores de Antígenos Quiméricos/imunologia , Síndrome da Liberação de Citocina/diagnóstico por imagem , Síndrome da Liberação de Citocina/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/imunologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: Toassess whether 18F-fluordeoxiglucose (18F-FDG) PET/MRI) with angiographic sequences can contribute to detecting vessel wall inflammation in patients with childhood-onset Takayasu's arteritis (c-TA) under immunosuppressive therapy. METHODS: A three-centre cross-sectional study was conducted. 18F-FDG PET/MRI scans were performed in c-TA patients and in oncologic patients, who served as the control group. Clinical and laboratory characteristics were also analysed. RESULTS: Seventeen c-TA patients (65% females) between the ages of 6 and 21 years with a mean disease duration of 9.4 years were recruited. Only one patient presented clinical disease activity and six (35.6%) had increased ESR and/or CRP levels. The most frequent magnetic resonance angiography (MRA) findings were stenosis and thickening, observed in 82.4 and 70.6% of c-TA patients, respectively. 18F-FDG PET revealed 18F-FDG uptake greater than the liver in at least one arterial segment in 15 (88.2%) patients in a qualitative analysis and a median maximum standardized uptake value (SUVmax) of 3.22 (interquartile range 2.76-3.69) in a semi-quantitative analysis. c-TA patients presented significantly higher SUVmax values than oncologic patients (P < 0.001). A positive correlation between SUVmax and CRP levels (ρ = 0.528, P = 0.029) was seen. CONCLUSION: A state-of-the-art imaging modality was used in c-TA patients and revealed a strong arterial FDG uptake even in patients in apparent remission. We suppose that this finding may represent silent activity in the vessel wall; however, we cannot exclude the possibility of arterial remodelling. Importantly, a negative imaging scan may help in immunosuppression withdrawal in daily clinical practice.