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The demand for sustainable and ethically farmed animal products is on the rise as consumers become more environmentally and animal welfare conscious. The need to diminish the consumption of soybean meal is urgent, and companies are looking for ways to respond to this necessity by looking for alternatives to soybean meal. This study assessed the impact of introducing whole dehydrated and live black soldier fly larvae (BSFL) into the diet of an indigenous chicken breed as environmental enrichment. A total of 144 39-day-old male Bianca di Saluzzo chickens were distributed among 18 pens and assigned to three different experimental groups. The control group received a diet where soybean meal was entirely replaced by alternative ingredients. The two experimental groups were given the same diet supplemented with 5% of the expected daily feed intake of whole dehydrated BSFL or whole live BSFL. Throughout the trial period (from the bird age of 39-174 days of age), live weight was recorded every 21 days, and the average daily gain, daily feed intake, and feed conversion ratio were calculated. The time required for the birds to consume the larvae was recorded three times a week. At age 147 and 174 days, 12 birds per treatment were selected based on mean live weight and slaughtered. Measurements included hot and chilled carcass weights, organ weights (spleen, liver, heart, stomach), breast and thigh muscle weights, and the corresponding yields were calculated. Acid protease activity was measured in proventriculus extract, and chitinase and chitosanase activity was calculated based on the release of reducing sugars from chitin or chitosan. The results showed little improvement in final live weights and daily feed intakes of the animals fed the insect larvae compared with control birds. Larva supplementation had no negative impact on the overall well-being of the animals assessed by blood analysis and histopathological assessment of the intestinal tract, spleen, and liver. No differences were found between the dehydrated vs live insect larvae consumption times, with all larvae being eaten up very rapidly (< 3 min). The birds fed BSFL showed an increase in chitinase activity. These findings support the potential use of whole BSFL as a form of environmental enrichment, particularly in their dehydrated form, being more convenient to use and store, which would also encourage the uptake of this practice by farmers.
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Ração Animal , Galinhas , Dieta , Larva , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/fisiologia , Larva/crescimento & desenvolvimento , Masculino , Ração Animal/análise , Dieta/veterinária , Simuliidae/fisiologia , Dípteros/fisiologia , Dípteros/crescimento & desenvolvimento , Trato Gastrointestinal/fisiologia , Quitinases/metabolismoRESUMO
BACKGROUND: Therapeutic ceiling of care is the maximum level of care deemed appropiate to offer to a patient based on their clinical profile and therefore their potential to derive benefit, within the context of the availability of resources. To our knowledge, there are no models to predict ceiling of care decisions in COVID-19 patients or other acute illnesses. We aimed to develop and validate a clinical prediction model to predict ceiling of care decisions using information readily available at the point of hospital admission. METHODS: We studied a cohort of adult COVID-19 patients who were hospitalized in 5 centres of Catalonia between 2020 and 2021. All patients had microbiologically proven SARS-CoV-2 infection at the time of hospitalization. Their therapeutic ceiling of care was assessed at hospital admission. Comorbidities collected at hospital admission, age and sex were considered as potential factors for predicting ceiling of care. A logistic regression model was used to predict the ceiling of care. The final model was validated internally and externally using a cohort obtained from the Leeds Teaching Hospitals NHS Trust. The TRIPOD Checklist for Prediction Model Development and Validation from the EQUATOR Network has been followed to report the model. RESULTS: A total of 5813 patients were included in the development cohort, of whom 31.5% were assigned a ceiling of care at the point of hospital admission. A model including age, COVID-19 wave, chronic kidney disease, dementia, dyslipidaemia, heart failure, metastasis, peripheral vascular disease, chronic obstructive pulmonary disease, and stroke or transient ischaemic attack had excellent discrimination and calibration. Subgroup analysis by sex, age group, and relevant comorbidities showed excellent figures for calibration and discrimination. External validation on the Leeds Teaching Hospitals cohort also showed good performance. CONCLUSIONS: Ceiling of care can be predicted with great accuracy from a patient's clinical information available at the point of hospital admission. Cohorts without information on ceiling of care could use our model to estimate the probability of ceiling of care. In future pandemics, during emergency situations or when dealing with frail patients, where time-sensitive decisions about the use of life-prolonging treatments are required, this model, combined with clinical expertise, could be valuable. However, future work is needed to evaluate the use of this prediction tool outside COVID-19.
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COVID-19 , Hospitalização , Humanos , COVID-19/epidemiologia , COVID-19/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hospitalização/estatística & dados numéricos , Espanha/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , SARS-CoV-2 , ComorbidadeRESUMO
The efficient removal of volatile sulfur compounds (VSCs), such as dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS), is crucial due to their foul odor and corrosive potential in sewer systems. Biofilters (BFs) offer promise for VSCs removal, but face challenges related to pH control and changing conditions at full scale. Two BFs, operated under acidophilic conditions for 78 days, were evaluated for their performance at varying inlet concentrations and empty bed residence times (EBRTs). BF1, incorporating 4-6 mm marble limestone for pH control, outperformed BF2, which used NaHCO3 in the nutrient solution. BF1 displayed better resilience, maintained a stable pH of 4.6 ± 0.6, and achieved higher maximum elimination capacities (ECmax, 41 mg DMS m-3 h-1 (RE 38.3%), 146 mg DMDS m-3 h-1 (RE 83.1%), 47 mg DMTS m-3 h-1 (RE 93.1%)) at an EBRT of 56 s compared to BF2 (9 mg DMS m-3 h-1 (RE 7.1%), 9 mg DMDS m-3 h-1 (RE 4.8%) and 11 mg DMTS m-3 h-1 (RE 26.6%)). BF2 exhibited pH stratification and decreased performance after feeding interruptions. The biodegradability of VSCs followed the order DMTS > DMDS > DMS, and several microorganisms were identified contributing to VSCs degradation in BF1, including Bacillus (14%), Mycobacterium (11%), Acidiphilium (7%), and Acidobacterium (3%).
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Dissulfetos , Filtração , Sulfetos , Sulfetos/química , Concentração de Íons de HidrogênioRESUMO
The removal of volatile methyl siloxanes (VMS) from landfill biogas is crucial for clean energy utilization. VMS are usually found together with aromatic compounds in landfill biogas of which toluene is the major representative. In the present study, two biofilters (BFs) packed with either woodchips and compost (WC) or perlite (PER) were used to study the (co-) removal of octamethyltrisiloxane (L3) and octamethylcyclotetrasiloxane (D4) from gas in presence and absence of toluene, used as a representative aromatic compound. The presence of low inlet toluene concentrations (315 ± 19 - 635 ± 80 mg toluene m-3) enhanced the VMS elimination capacity (EC) in both BFs by a factor of 1.8 to 12.6. The highest removal efficiencies for D4 (57.1 ± 1.1 %; EC = 0.12 ± 0.01 gD4 m-3 h-1) and L3 (52.0 ± 0.6 %; EC = 0.23 ± 0.01 gL3 m-3 h-1) were observed in the BF packed with WC. The first section of the BFs (EBRT = 9 min), where toluene was (almost) completely removed, accounted for the majority (87.7 ± 0.6 %) of the total VMS removal. Microbial analysis revealed the impact of VMS and toluene in the activated sludge, showing a clear selection for certain genera in samples influenced by VMS in the presence (X2) or absence (X1) of toluene, such as Pseudomonas (X1 = 0.91 and X2 = 12.0 %), Sphingobium (X1 = 0.09 and X2 = 4.04 %), Rhodococcus (X1 = 0.42 and X2 = 3.91 %), and Bacillus (X1 = 7.15 and X2 = 3.84 %). The significant maximum EC values obtained by the BFs (0.58 gVMS m-3 h-1) hold notable significance in a combined system framework as they could enhance the longevity of traditional physicochemical methods to remove VMS like activated carbon in diverse environmental scenarios.
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Biodegradação Ambiental , Siloxanas , Tolueno , Tolueno/metabolismo , Filtração/métodos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/metabolismo , MicrobiotaRESUMO
A family of stilbenyl-azopyrroles compounds 2a-d and 3a-d was efficiently obtained via a Mizoroki-Heck C-C-type coupling reaction between 2-(4'-iodophenyl-azo)-N-methyl pyrrole (1a) and different vinyl precursors. The influence of the π-conjugated backbone and the effect of the pyrrole moiety were correlated with their optical properties. Studies via UV-Visible spectrophotometry revealed that the inclusion of EWG or EDG favors a red-shift of the main absorption band in these azo compounds compared with their non-substituted analogues. Furthermore, there is a clear influence between the half-life of the Z isomer formed by irradiation with white light and the push-pull behavior of the molecules. In several cases, the stilbenyl-azopyrroles led to the formation of J-type aggregates in binary MeOH : H2O solvents, which are of interest for water compatible applications.
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BACKGROUND: DESTINY-Breast03 is a randomized, multicenter, open-label, phase III study of trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. A statistically significant improvement in progression-free survival (PFS) versus T-DM1 was reported in the primary analysis. Here, we report exploratory efficacy data in patients with and without brain metastases (BMs) at baseline. PATIENTS AND METHODS: Patients were randomly assigned 1 : 1 to receive T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg. Patients with clinically inactive/asymptomatic BMs were eligible. Lesions were measured as per modified RECIST, version 1.1. Outcomes included PFS by blinded independent central review (BICR), objective response rate (ORR), and intracranial ORR as per BICR. RESULTS: As of 21 May 2021, 43/261 patients randomized to T-DXd and 39/263 patients randomized to T-DM1 had BMs at baseline, as per investigator assessment. Among patients with baseline BMs, 20/43 in the T-DXd arm and 19/39 in the T-DM1 arm had not received prior local BM treatment. For patients with BMs, median PFS was 15.0 months [95% confidence interval (CI) 12.5-22.2 months] for T-DXd versus 3.0 months (95% CI 2.8-5.8 months) for T-DM1; hazard ratio (HR) 0.25 (95% CI 0.13-0.45). For patients without BMs, median PFS was not reached (95% CI 22.4 months-not estimable) for T-DXd versus 7.1 months (95% CI 5.6-9.7 months) for T-DM1; HR 0.30 (95% CI 0.22-0.40). Confirmed systemic ORR was 67.4% for T-DXd versus 20.5% for T-DM1 and 82.1% for T-DXd versus 36.6% for T-DM1 for patients with and without BMs, respectively. Intracranial ORR was 65.7% with T-DXd versus 34.3% with T-DM1. CONCLUSIONS: Patients with HER2-positive mBC whose disease progressed after trastuzumab and a taxane achieved a substantial benefit from treatment with T-DXd compared with T-DM1, including those with baseline BMs.
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Ado-Trastuzumab Emtansina , Neoplasias Encefálicas , Neoplasias da Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Pessoa de Meia-Idade , Ado-Trastuzumab Emtansina/uso terapêutico , Ado-Trastuzumab Emtansina/farmacologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Imunoconjugados/uso terapêutico , Imunoconjugados/farmacologia , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Immune checkpoint inhibitors improve the efficacy of first-line chemotherapy for patients with programmed death-ligand 1 (PD-L1)-positive unresectable locally advanced/metastatic triple-negative breast cancer (aTNBC), but randomised data in rapidly relapsing aTNBC are scarce. PATIENTS AND METHODS: IMpassion132 (NCT03371017) enrolled patients with aTNBC relapsing <12 months after last chemotherapy dose (anthracycline and taxane required) or surgery for early TNBC. PD-L1 status was centrally assessed using SP142 before randomisation. Initially patients were enrolled irrespective of PD-L1 status. From August 2019, enrolment was restricted to PD-L1-positive (tumour immune cell ≥1%) aTNBC. Patients were randomised 1:1 to placebo or atezolizumab 1200 mg every 21 days with investigator-selected chemotherapy until disease progression or unacceptable toxicity. Stratification factors were chemotherapy regimen (carboplatin plus gemcitabine or capecitabine monotherapy), visceral (lung and/or liver) metastases and (initially) PD-L1 status. The primary endpoint was overall survival (OS), tested hierarchically in patients with PD-L1-positive tumours and then, if positive, in the modified intent-to-treat (mITT) population (all-comer patients randomised pre-August 2019). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. RESULTS: Among 354 patients with rapidly relapsing PD-L1-positive aTNBC, 68% had a disease-free interval of <6 months and 73% received carboplatin/gemcitabine. The OS hazard ratio was 0.93 (95% confidence interval 0.73-1.20, P = 0.59; median 11.2 months with placebo versus 12.1 months with atezolizumab). mITT and subgroup results were consistent. Median PFS was 4 months across treatment arms and populations. ORRs were 28% with placebo versus 40% with atezolizumab. Adverse events (predominantly haematological) were similar between arms and as expected with atezolizumab plus carboplatin/gemcitabine or capecitabine following recent chemotherapy exposure. CONCLUSIONS: OS, which is dismal in patients with TNBC relapsing within <12 months, was not improved by adding atezolizumab to chemotherapy. A biology-based definition of intrinsic resistance to immunotherapy in aTNBC is urgently needed to develop novel therapies for these patients in next-generation clinical trials.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Gencitabina , Recidiva Local de Neoplasia , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Método Duplo-Cego , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Adulto , Carboplatina/administração & dosagem , Capecitabina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Intervalo Livre de Progressão , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversosRESUMO
Introducción: La SPECT portátil puede ser una técnica de imagen útil para la planificación preoperatoria de la biopsia selectiva del ganglio centinela (BSGC) ya que permite la localización del ganglio centinela (GC) mediante imágenes tomográficas en 3D y en tiempo real y determina su profundidad, después de unos minutos de exploración. El objetivo del estudio fue evaluar la correlación entre el número de GC detectados entre las imágenes de la SPECT portátil y la linfogammagrafía (LG). Materiales y métodos: Cien pacientes con diagnóstico de cáncer de mama infiltrante y sin evidencia clínica de afectación ganglionar, se sometieron prospectivamente a una BSGC. El estudio preoperatorio incluyó imágenes de SPECT portátil a los 15 min tras la inyección y de LG a los 25 y 60-90 min (precoz y tardía). Se analizó el acuerdo observado y se realizó un estudio de concordancia entre el número de GC detectados con SPECT portátil y LG. Resultados: El acuerdo observado en la detección de GC entre SPECT portátil y LG precoz fue del 72%; entre SPECT portátil y LG tardía del 85%, y entre la LG precoz y la tardía de un 87%. En el estudio de concordancia se registró una concordancia moderada entre la SPECT portátil y la LG precoz (coeficiente kappa: 0,42); una concordancia moderada-alta entre la SPECT portátil y la LG tardía (coeficiente kappa: 0,60), y una concordancia de moderada-alta entre la LG precoz y la tardía (coeficiente kappa: 0,70), sin diferencias significativas entre ellos (valor p=0,16). Conclusión: La SPECT portátil presentó una concordancia moderada-alta con los estudios de imagen convencional y podría ser una alternativa válida para el estudio prequirúrgico de la BSGC en el cáncer de mama.(AU)
Introduction: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods: One hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 6090min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. Results: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). Conclusion: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.(AU)
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Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Cintilografia , Linfonodo Sentinela/diagnóstico por imagem , Biópsia de Linfonodo Sentinela , Linfocintigrafia , Medicina Nuclear , Imagem MolecularRESUMO
BACKGROUND: The incorporation of circulating tumor DNA (ctDNA) into the management of operable breast cancer (BC) has been hampered by the heterogeneous results from different studies. We aimed to assess the prognostic value of ctDNA in patients with operable (non metastatic) BC. MATERIALS AND METHODS: A systematic search of databases (PubMed/Medline, Embase, and CENTRAL) and conference proceedings was conducted to identify studies reporting the association of ctDNA detection with disease-free survival (DFS) and overall survival (OS) in patients with stage I-III BC. Log-hazard ratios (HRs) were pooled at each timepoint of ctDNA assessment (baseline, after neoadjuvant therapy, and follow-up). ctDNA assays were classified as primary tumor-informed and non tumor-informed. RESULTS: Of the 3174 records identified, 57 studies including 5779 patients were eligible. In univariate analyses, ctDNA detection was associated with worse DFS at baseline [HR 2.98, 95% confidence interval (CI) 1.92-4.63], after neoadjuvant therapy (HR 7.69, 95% CI 4.83-12.24), and during follow-up (HR 14.04, 95% CI 7.55-26.11). Similarly, ctDNA detection at all timepoints was associated with worse OS (at baseline: HR 2.76, 95% CI 1.60-4.77; after neoadjuvant therapy: HR 2.72, 95% CI 1.44-5.14; and during follow-up: HR 9.19, 95% CI 3.26-25.90). Similar DFS and OS results were observed in multivariate analyses. Pooled HRs were numerically higher when ctDNA was detected at the end of neoadjuvant therapy or during follow-up and for primary tumor-informed assays. ctDNA detection sensitivity and specificity for BC recurrence ranged from 0.31 to 1.0 and 0.7 to 1.0, respectively. The mean lead time from ctDNA detection to overt recurrence was 10.81 months (range 0-58.9 months). CONCLUSIONS: ctDNA detection was associated with worse DFS and OS in patients with operable BC, particularly when detected after treatment and using primary tumor-informed assays. ctDNA detection has a high specificity for anticipating BC relapse.
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Neoplasias da Mama , DNA Tumoral Circulante , Recidiva Local de Neoplasia , Humanos , DNA Tumoral Circulante/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Prognóstico , Biomarcadores Tumorais/sangue , Terapia Neoadjuvante/métodos , Intervalo Livre de DoençaRESUMO
BACKGROUND: The HER2DX risk-score has undergone rigorous validation in prior investigations involving patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer. In this study, we present the outcomes of the HER2DX risk-score within the most recent release of the Sweden Cancerome Analysis Network-Breast (SCAN-B) HER2+ cohort. This updated examination benefits from a larger patient sample, an extended follow-up duration, and detailed treatment information. MATERIALS AND METHODS: Clinical and RNAseq data from the SCAN-B dataset were retrieved from Gene Expression Omnibus (GSE81538). Among the 6600 patients, 819 had HER2+ breast cancer, with 757 individuals with research-based HER2DX risk-scores and corresponding survival outcomes. The HER2DX risk-score was evaluated (i) as a continuous variable and (ii) using predefined cut-offs. The primary endpoint for this study was overall survival (OS). The Kaplan-Meier method and Cox models were used to estimate OS and a multistate model with four states was fitted to better characterize patients' follow-up. RESULTS: The median follow-up time was 7.5 years (n = 757). The most common systemic therapy was chemotherapy with trastuzumab (82.0%) and most tumors were classified as T1-T2 (97.1%). The HER2DX risk-score as a continuous variable was significantly associated with OS after adjustment for clinical variables and treatment regimen [hazard ratios (HR) per 10-unit increment = 1.31, 95% confidence interval (CI) 1.13-1.51, P < 0.001] as well as within predefined risk groups (high versus low; HR = 2.57, 95% CI 1.36-4.85, P < 0.001). Patients classified as HER2DX high-risk also had higher risk of (i) breast cancer recurrence and (ii) death without previous recurrence. Within the subgroup of HER2+ T1N0 tumors (n = 297), those classified as high-risk demonstrated inferior OS compared to low-risk tumors (7-year OS 77.8% versus 96.8%, P < 0.001). The HER2DX mRNA ERBB2 score was associated with clinical HER2 status (area under the receiver operating characteristic curve = 0.91). CONCLUSIONS: In patients with early-stage HER2+ breast cancer, HER2DX risk-score provides prognostic information beyond clinicopathological variables, including treatment regimen with or without trastuzumab.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Prognóstico , Suécia/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Trastuzumab/farmacologia , Trastuzumab/uso terapêuticoRESUMO
BACKGROUND: 18F-fluoroestradiol (FES) positron emission tomography (PET)/computed tomography (CT) is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the endocrine therapy (ET)-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). PATIENTS AND METHODS: Eligible patients underwent an 18F-FES PET/CT at baseline. Patients with standardized uptake value (SUV) ≥ 2 received single-agent ET until progressive disease; patients with SUV < 2 were randomized to single-agent ET (arm A) or chemotherapy (ChT) (arm B). The primary objective was to compare the activity of first-line ET versus ChT in patients with 18F-FES SUV < 2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV ≥ 2 and received ET; 30 patients with SUV < 2 were randomized to ET or ChT. After a median follow-up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median progression-free survival (PFS) was 12.4 months [95% confidence interval (CI) 3.1-59.6 months] in patients with SUV < 2 randomized to arm A versus 23.0 months (95% CI 7.7-30.0 months) in arm B, [hazard (HR) = 0.71, 95% CI 0.3-1.7 months]; median PFS was 18.0 months (95% CI 11.2-23.1 months) in patients with SUV ≥ 2 treated with ET. Median overall survival (OS) was 28.2 months (95% CI 14.2 months-not estimable) in patients with SUV < 2 randomized to ET (arm A) versus 52.8 months (95% CI 16.2 months-not estimable) in arm B (ChT). Median OS was not reached in patients with SUV ≥ 2. 60-month OS rate was 41.6% (95% CI 10.4% to 71.1%) in arm A, 42.0% (95% CI 14.0% to 68.2%) in arm B, and 59.6% (95% CI 48.6% to 69.0%) in patients with SUV ≥ 2. In patients with SUV ≥ 2, 60-month OS rate was 72.6% if treated with aromatase inhibitors (AIs) versus 40.6% in case of fulvestrant or tamoxifen (P < 0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.
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Neoplasias da Mama , Estradiol , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptor ErbB-2 , Receptores de Estrogênio , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Estradiol/análogos & derivados , Projetos Piloto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Compostos Radiofarmacêuticos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Estudos ProspectivosRESUMO
BACKGROUND: KEYNOTE-522 demonstrated statistically significant improvements in pathological complete response (pCR) with neoadjuvant pembrolizumab plus chemotherapy and event-free survival (EFS) with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab in patients with high-risk, early-stage triple-negative breast cancer (TNBC). Prior studies have shown the prognostic value of the residual cancer burden (RCB) index to quantify the extent of residual disease after neoadjuvant chemotherapy. In this preplanned exploratory analysis, we assessed RCB distribution and EFS within RCB categories by treatment group. PATIENTS AND METHODS: A total of 1174 patients with stage T1c/N1-2 or T2-4/N0-2 TNBC were randomized 2 : 1 to pembrolizumab 200 mg or placebo every 3 weeks given with four cycles of paclitaxel + carboplatin, followed by four cycles of doxorubicin or epirubicin + cyclophosphamide. After surgery, patients received pembrolizumab or placebo for nine cycles or until recurrence or unacceptable toxicity. Primary endpoints are pCR and EFS. RCB is a prespecified exploratory endpoint. The association between EFS and RCB was assessed using a Cox regression model. RESULTS: Pembrolizumab shifted patients into lower RCB categories across the entire spectrum compared with placebo. There were more patients in the pembrolizumab group with RCB-0 (pCR), and fewer patients in the pembrolizumab group with RCB-1, RCB-2, and RCB-3. The corresponding hazard ratios (95% confidence intervals) for EFS were 0.70 (0.38-1.31), 0.92 (0.39-2.20), 0.52 (0.32-0.82), and 1.24 (0.69-2.23). The most common first EFS events were distant recurrences, with fewer in the pembrolizumab group across all RCB categories. Among patients with RCB-0/1, more than half [21/38 (55.3%)] of all events were central nervous system recurrences, with 13/22 (59.1%) in the pembrolizumab group and 8/16 (50.0%) in the placebo group. CONCLUSIONS: Addition of pembrolizumab to chemotherapy resulted in fewer EFS events in the RCB-0, RCB-1, and RCB-2 categories, with the greatest benefit in RCB-2. These findings demonstrate that pembrolizumab not only increased pCR rates, but also improved EFS among most patients who do not have a pCR.
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Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasia Residual , Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Residual/patologia , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Carboplatina/administração & dosagem , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/efeitos adversos , Idoso , Adulto , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Epirubicina/uso terapêutico , Intervalo Livre de Progressão , Quimioterapia Adjuvante/métodos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Método Duplo-CegoRESUMO
INTRODUCTION: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). MATERIALS AND METHODS: 100 patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60-90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. RESULTS: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). CONCLUSION: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.
Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Linfonodo Sentinela/diagnóstico por imagem , Linfonodo Sentinela/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Linfonodos/patologiaRESUMO
Biogas serves as a crucial renewable energy vector to ensure a more sustainable energy future. However, the presence of hydrogen sulfide (H2S) limits its application in various sectors, emphasizing the importance of effective H2S removal techniques for maximizing its potential. In the present study, the limits of a pilot-scale bioscrubber for biogas desulfurization was study in a real scenario. An increase in the superficial liquid velocity resulted in significant improvements in the H2S removal efficiency, increasing from 76 ± 8% (elimination capacity of 6.2 ± 0.5 gS-H2S m-3 h-1) to 97.7 ± 0.5% (elimination capacity of 8 ± 1 gS-H2S m-3 h-1) as the superficial liquid velocity increased from 50 ± 3 m h-1 to 200 ± 8 m h-1. A USL of 161.4 ± 0.5 m h-1 was able to achieve outlet H2S concentrations as low as 3 ± 1 ppmv (H2S removal efficiency of 97 ± 1%) for 7 days. High superficial liquid velocity favoured the aerobic H2S oxidation reducing the nitrate demand. The maximum EC reached throughout the operation was 50.8 ± 0.6 gS-H2S m-3 h-1 (H2S removal efficiency of 96 ± 1%) and a sulfur production of 60%. Studies in batch flocculation experiments showed sulfur removal rates up to 97.6 ± 0.9% with a cationic flocculant dose of 75 mg L-1. Microbial analysis revealed that the predominant genus with sulfo-oxidant capacity during periods of low H2S inlet load was Thioalkalispira-sulfurivermis (61-69%), while in periods of higher H2S inlet load, family Arcobacteraceae was the most prevalent (11%).
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Reatores Biológicos , Sulfeto de Hidrogênio , Biocombustíveis , Enxofre , Instalações de Eliminação de ResíduosRESUMO
PURPOSE OF REVIEW: The purpose of this review is to update the information about the different types of reconstruction after partial nephrectomy, with special emphasis on the new methods of suture-free hemostasis currently available. RECENT FINDINGS: The aim of renal reconstruction is to avoid bleeding and leakage of the collecting system, but now the renorrhaphy technique used is considered one of the modifiable determinants of renal function after surgery. In an attempt to avoid the loss of renal function implicit in classic reconstruction, new techniques have been described to control hemostasis and urinary leakage, which employ fewer suture layers, different suture materials and designs, and a wide range of commercially available hemostatic materials. Multiple suture characteristics have been studied as a potential factor influencing the renal function observed after partial nephrectomy. Single-plane suture techniques, the use of bearded sutures, and running sutures seem to be associated with less deterioration in postoperative renal function, and deep medullary sutures should be avoided to avoid affecting the arcuate arteries. Sutureless hemostasis systems could prevent the deterioration of renal function and complications derived from suturing, also reducing ischemia time and surgical time without increasing the risk of complications.
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Neoplasias Renais , Laparoscopia , Humanos , Nefrectomia/métodos , Rim/cirurgia , Neoplasias Renais/cirurgia , Perda Sanguínea Cirúrgica/prevenção & controle , Técnicas de SuturaRESUMO
The current treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) has been greatly impacted in the past decade by the introduction of antibody-drug conjugates (ADCs), which represent a relatively novel therapeutic class with the peculiar ability to deliver otherwise overtly toxic chemotherapeutics to tumor sites by exploiting the specificities of monoclonal antibodies. Indeed, drug engineering refinements in ADC design, such as through the introduction of cleavable linkers and hydrophobic payloads, resulted in improved patient outcomes in recent years. Two different ADCs, namely trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), have already entered clinical practice for the treatment of HER2-positive ABC. In this scenario, T-DXd has shown to portend better survival outcomes compared to T-DM1, while leaving a large unsought area of unmet medical need upon T-DXd failure. Treatment decision and benefit of cancer drugs following T-DXd still represent an area of clinical controversy, where a preclinical investigation and clinical development should be prioritized. As the pace of innovation is currently accelerating, and with novel ADC formulations advancing in early-phase clinical trials, the whole BC field is changing at an unprecedented rate, with potential broadenings of therapeutic indications. In this review, we present the clinical landscape of HER2-positive advanced BC and discuss our vision on how to tackle T-DXd resistance, providing a perspective on the priority areas of the cancer research in this setting.
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Neoplasias da Mama , Imunoconjugados , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Ado-Trastuzumab Emtansina/farmacologia , Ado-Trastuzumab Emtansina/uso terapêutico , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêuticoRESUMO
Human epidermal growth factor receptor 2 (HER2)-low breast cancer has recently emerged as a targetable subset of breast tumors, based on the evidence from clinical trials of novel anti-HER2 antibody-drug conjugates. This evolution has raised several biological and clinical questions, warranting the establishment of consensus to optimally treat patients with HER2-low breast tumors. Between 2022 and 2023, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process focused on HER2-low breast cancer. The consensus included a multidisciplinary panel of 32 leading experts in the management of breast cancer from nine different countries. The aim of the consensus was to develop statements on topics that are not covered in detail in the current ESMO Clinical Practice Guideline. The main topics identified for discussion were (i) biology of HER2-low breast cancer; (ii) pathologic diagnosis of HER2-low breast cancer; (iii) clinical management of HER2-low metastatic breast cancer; and (iv) clinical trial design for HER2-low breast cancer. The expert panel was divided into four working groups to address questions relating to one of the four topics outlined above. A review of the relevant scientific literature was conducted in advance. Consensus statements were developed by the working groups and then presented to the entire panel for further discussion and amendment before voting. This article presents the developed statements, including findings from the expert panel discussions, expert opinion, and a summary of evidence supporting each statement.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Consenso , OncologiaRESUMO
BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.