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Plastic production reached 400 million tons in 2022 (ref. 1), with packaging and single-use plastics accounting for a substantial amount of this2. The resulting waste ends up in landfills, incineration or the environment, contributing to environmental pollution3. Shifting to biodegradable and compostable plastics is increasingly being considered as an efficient waste-management alternative4. Although polylactide (PLA) is the most widely used biosourced polymer5, its biodegradation rate under home-compost and soil conditions remains low6-8. Here we present a PLA-based plastic in which an optimized enzyme is embedded to ensure rapid biodegradation and compostability at room temperature, using a scalable industrial process. First, an 80-fold activity enhancement was achieved through structure-based rational engineering of a new hyperthermostable PLA hydrolase. Second, the enzyme was uniformly dispersed within the PLA matrix by means of a masterbatch-based melt extrusion process. The liquid enzyme formulation was incorporated in polycaprolactone, a low-melting-temperature polymer, through melt extrusion at 70 °C, forming an 'enzymated' polycaprolactone masterbatch. Masterbatch pellets were integrated into PLA by melt extrusion at 160 °C, producing an enzymated PLA film (0.02% w/w enzyme) that fully disintegrated under home-compost conditions within 20-24 weeks, meeting home-composting standards. The mechanical and degradation properties of the enzymated film were compatible with industrial packaging applications, and they remained intact during long-term storage. This innovative material not only opens new avenues for composters and biomethane production but also provides a feasible industrial solution for PLA degradation.
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Plásticos Biodegradáveis , Biodegradação Ambiental , Enzimas Imobilizadas , Hidrolases , Poliésteres , Engenharia de Proteínas , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/metabolismo , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Hidrolases/metabolismo , Hidrolases/química , Poliésteres/química , Poliésteres/metabolismo , Solo/química , Temperatura , Estabilidade Enzimática , CompostagemRESUMO
Microalgae are emerging as a promising feedstock for bioplastics, with Chlorella vulgaris yielding significant amounts of starch. This polysaccharide is convertible into thermoplastic starch (TPS), a biodegradable plastic of industrial relevance. In this study, we developed a pilot-scale protocol for extracting and purifying starch from 430 g (dry weight - DW) of starch-enriched Chlorella vulgaris biomass. More than 200 gDW of starch were recovered, with an extraction yield and starch purity degree reaching 98 and 87 %, respectively. We have characterized this extracted starch and processed it into TPS using twin-screw extrusion and injection molding. Microalgal starch showed similar properties to those of native plant starch, but with smaller granules. We compared the mechanical properties of microalgal TPS with two controls, namely a commercial TPS and a TPS prepared from commercial potato starch granules. TPS prepared from microalgal starch showed a softer and more ductile behavior compared to the reference materials. This study demonstrates the feasibility of recovering high-purity microalgal starch at pilot scale with high yields, and highlights the potential of microalgal starch for the production of TPS using industrially relevant processes.
Assuntos
Chlorella vulgaris , Microalgas , Amido , Amido/química , Amido/metabolismo , Chlorella vulgaris/metabolismo , Chlorella vulgaris/química , Microalgas/metabolismo , Microalgas/química , Biomassa , Plásticos Biodegradáveis/química , TemperaturaRESUMO
Following blastocyst hatching, ungulate embryos undergo a prolonged preimplantation period termed conceptus elongation. Conceptus elongation constitutes a highly susceptible period for embryonic loss and the embryonic requirements during this process are largely unknown, but multiple lipid compounds have been identified in the fluid nourishing the elongating conceptuses. Peroxisome proliferator-activated receptors (PPARs) mediate the signaling actions of prostaglandins and other lipids and, between them, PPARG has been pointed out to play a relevant role on conceptus elongation by a functional study that depleted PPARG in both uterus and conceptus. The objective of this study has been to determine if embryonic PPARG is required for bovine embryo development. To that aim, we have generated bovine PPARG KO embryos in vitro by two independent gene ablation strategies and assess their developmental ability. In vitro development to Day (D) 8 blastocyst was unaffected by PPARG ablation, as total, inner cell mass and trophectoderm cell numbers were similar between WT and KO D8 embryos. In vitro post-hatching development to D12 was also comparable between different genotypes, as embryo diameter, epiblast cell number, and embryonic disc formation and hypoblast migration rates were unaffected by the ablation. The development to tubular stages equivalent to E14 was assessed in vivo, following a heterologous embryo transfer experiment, observing that the development of extra-embryonic membranes and of the embryonic disc was not altered by PPARG ablation. In conclusion, PPARG ablation did not impaired bovine embryo development up to tubular stages.
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Massive genotyping in cattle has uncovered several deleterious haplotypes that cause preterm mortality. Holstein haplotype 5 (HH5) is a deleterious haplotype present in the Holstein Friesian population that involves the ablation of the transcription factor B1 mitochondrial (TFB1M) gene. The developmental stage at which HH5 double-carrier (DC, homozygous) embryos or fetuses die remains unknown and this is a relevant information to estimate the economic losses associated with the inadvertent cross between carriers. To determine whether HH5 DC survive to maternal recognition of pregnancy, embryonic day (E) 14 embryos were flushed from superovulated carrier cows inseminated with a carrier bull. Double-carrier E14 conceptuses were recovered at Mendelian rates but they failed to achieve early elongation, as evidenced by a drastic reduction of their extra-embryonic membranes, which were >26-fold shorter than those of carrier or noncarrier embryos. To assess development at earlier stages, TFB1M knockout (KO) embryos-functionally equivalent to DC embryos-were generated by clustered regularly interspaced short palindromic repeats (CRISPR) technology and cultured to the blastocyst stage, in vitro culture day (D) 8, and to the early embryonic disc stage, D12. No significant effect of TFB1M ablation was observed on the differentiation and proliferation of embryonic lineages and relative mitochondrial DNA (mtDNA) content up to D12. In conclusion, HH5 DC embryos are able to develop to early embryonic disc stage but fail to undergo early conceptus elongation, which is required for pregnancy recognition.
Assuntos
Haplótipos , Animais , Feminino , Bovinos , Gravidez , Desenvolvimento Embrionário , DNA Mitocondrial/genéticaRESUMO
El presente reporte tiene como objetivo presentar de manera secuencial y visual la protracción maxilar de un paciente clase III esqueletal, utilizando el protocolo BAMP. Una vez realizado el análisis clínico del caso se decidió realiza un tratamiento ortopédico a través del uso de miniplacas de titanio con elásticos intermaxilares de clase III siguiendo el protocolo BAMP, junto a un tratamiento ortodóncico dento alveolar con aparatología fija bimaxilar prescripción Roth 0.22" Mini sprint forestadent. Se observa el éxito del enfoque interceptivo utilizando el protocolo BAMP. Este enfoque logró reducir tanto el tiempo como la complejidad del tratamiento ortodóncico, y también disminuyó la necesidad de someterse a una cirugía ortognática en la edad adulta. El tratamiento BAMP, diseñado para ciertas edades y crecimiento, se demostró exitoso en un paciente de 12 años sin potencial de crecimiento. Las miniplacas como anclaje son efectivas para protracción maxilar en varios casos, aunque se necesita seguimiento y educación postquirúrgica. Se recomienda retirar las miniplacas cuando no sean necesarias, adaptando el protocolo a cada paciente. En resumen, el tratamiento con miniplacas es eficaz para corregir anomalías Clase III esqueléticas.
The present report aims to sequentially and visually present the maxillary protraction of a Class III skeletal patient using the BAMP protocol. After conducting a clinical analysis of the case, it was decided to perform orthopedic treatment using titanium miniplates with Class III intermaxillary elastics following the BAMP protocol, in conjunction with dentoalveolar orthodontic treatment using fixed bimaxillary appliances with Roth prescription 0.022" Mini Sprint Forestadent. The success of the interceptive approach using the BAMP protocol is observed. This approach managed to reduce both the time and complexity of orthodontic treatment and also decreased the need for orthognathic surgery in adulthood. The BAMP treatment, designed for specific ages and growth stages, proved successful in a 12-year-old patient without growth potential. Miniplates as anchorage are effective for maxillary protraction in various cases, although post-surgical follow-up and education are required. It is recommended to remove the miniplates when they are no longer necessary, adapting the protocol to each patient. In summary, miniplate treatment is effective in correcting Class III skeletal anomalies.
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Rabbits constitute an interesting model to understand gamete interaction and test novel Artificial Reproductive Techniques, but in vitro fertilization (IVF) is particularly problematic in this species. We have conducted a series of experiments to develop a consistent IVF technique. Initially, we checked viability, acrosome integrity, capacitation and motility in ejaculated sperm purified by a density gradient and incubated at different times in three different media: Tyrode's Albumin Lactate Pyruvate (TALP), human tubal fluid (HTF), and Brackett and Oliphant (BO). Total and progressive motility at 10-24 h and linearity from 3 h onwards was significantly higher in BO medium compared to TALP and HTF. Subsequently, cumulus-oocyte complexes (COCs) collected 10 h after induction of ovulation were incubated with sperm in TALP, HTF or BO for 18 h with or without performing sperm pre-incubation for 6 h. Pronuclear formation rate at 18 h was significantly higher in BO compared to other media (â¼84 % vs. 17-22 %) and was not improved by pre-incubation. As COCs recovery rate was low at 10 h after induction of ovulation, COCs were collected at 12 h and co-incubated with sperm in BO. Pronuclear formation rate was similar than those obtained in COCs collected at 10 h (â¼85 %), and when embryos were allowed to develop in vitro, the protocol yielded high cleavage and blastocyst rates (91 and 59 %, respectively). In conclusion, ejaculated rabbit sperm purified in a density gradient fertilize efficiently COCs collected at 12 h in BO medium.
Assuntos
Fertilização in vitro , Sêmen , Feminino , Coelhos , Masculino , Humanos , Animais , Fertilização in vitro/veterinária , Fertilização in vitro/métodos , Acrossomo , Espermatozoides , Oócitos , Albuminas , Capacitação EspermáticaRESUMO
CONTEXT: Arachidonic acid (AA) is the precursor of prostaglandins, which may play autocrine roles during early embryo development. AIMS: To test the developmental effects of addition of AA to pre- and post-hatching culture media on in vitro -produced bovine embryos. METHODS: Pre-hatching effects of AA were tested by culturing bovine zygotes in synthetic oviductal fluid (SOF) supplemented with 100 or 333µM AA. Post-hatching effects of AA were tested by culturing Day 7 blastocysts in N2B27 supplemented with 5, 10, 20 or 100µM AA up to Day 12. KEY RESULTS: Pre-hatching development to blastocyst was completely abrogated at 333µM AA, whereas blastocyst rates and cell numbers were not altered at 100µM AA. Impaired post-hatching development was observed at 100µM AA, whereas no effect on survival rates was noted at 5, 10 and 20µM AA. However, a significant reduction in Day 12 embryo size was observed at 10 and 20µM AA. Hypoblast migration, epiblast survival and formation of embryonic-disc-like structures were unaffected at 5-10µM AA. AA exposure downregulated the genes PTGIS , PPARG , LDHA and SCD in Day 12 embryos. CONCLUSIONS: Pre-hatching embryos are mostly irresponsive to AA, whereas AA was observed to have negative effects during early post-hatching development. IMPLICATIONS: AA does not improve in vitro bovine embryo development and is not required up to early post-hatching stages.
Assuntos
Blastocisto , Fertilização in vitro , Animais , Bovinos , Ácido Araquidônico/farmacologia , Fertilização in vitro/veterinária , Embrião de Mamíferos , Desenvolvimento Embrionário , Técnicas de Cultura Embrionária/veterináriaRESUMO
PUF60-related developmental disorder (also referred to as Verheij syndrome), resulting from haploinsufficiency of PUF60, is associated with multiple congenital anomalies affecting a wide range of body systems. These anomalies include ophthalmic coloboma, and congenital anomalies of the heart, kidney, and musculoskeletal system. Behavioral and intellectual difficulties are also observed. While less common than other features associated with PUF60-related developmental disorder, for instance hearing impairment and short stature, identification of specific anomalies such as ophthalmic coloboma can aid with diagnostic identification given the limited spectrum of genes linked with this feature. We describe 10 patients with PUF60 gene variants, bringing the total number reported in the literature, to varying levels of details, to 56 patients. Patients were recruited both via locally based exome sequencing from international sites and from the DDD study in the United Kingdom. Eight of the variants reported were novel PUF60 variants. The addition of a further patient with a reported c449-457del variant to the existing literature highlights this as a recurrent variant. One variant was inherited from an affected parent. This is the first example in the literature of an inherited variant resulting in PUF60-related developmental disorder. Two patients (20%) were reported to have a renal anomaly consistent with 22% of cases in previously reported literature. Two patients received specialist endocrine treatment. More commonly observed were clinical features such as: cardiac anomalies (40%), ocular abnormalities (70%), intellectual disability (60%), and skeletal abnormalities (80%). Facial features did not demonstrate a recognizable gestalt. Of note, but remaining of unclear causality, we describe a single pediatric patient with pineoblastoma. We recommend that stature and pubertal progress should be monitored in PUF60-related developmental disorder with a low threshold for endocrine investigations as hormone therapy may be indicated. Our study reports an inherited case with PUF60-related developmental disorder which has important genetic counseling implications for families.
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Anormalidades Múltiplas , Coloboma , Cardiopatias Congênitas , Deficiência Intelectual , Criança , Humanos , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Deficiências do Desenvolvimento/genética , Cardiopatias Congênitas/genética , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genéticaRESUMO
Abdominal aortic aneurysm is defined as a dilatation of the abdominal aorta greater than 3cm. Its prevalence is between 1 and 1.5 cases per 100 people, constituting an important cause of morbidity and mortality. Rare in women, its frequency increases with age and its most frequent location is between the renal arteries and the aorto-iliac bifurcation. Approximately 5% of cases will involve the visceral branches. It is a silent pathological process whose natural evolution is rupture, which often has a fatal outcome and whose diagnosis is part of the pathology that we will find in emergency radiology. The involvement of the radiologist and the preparation of an accurate diagnostic report, as soon as possible, is essential for decision-making by the team in charge of the patient's surgery.
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Aneurisma da Aorta Abdominal , Ruptura Aórtica , Cirurgiões , Humanos , Feminino , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/cirurgia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Prevalência , RadiologistasRESUMO
Ungulate embryos undergo critical cell differentiation and proliferation events around and after blastocyst hatching. Failures in these processes lead to early pregnancy losses, which generate an important economic impact on farming. Conventional embryo culture media, such as SOF, are unable to support embryo development beyond hatching. In contrast, N2B27 medium supports early post-hatching development, evidencing a swift in embryonic nutritional requirements during this developmental window. Here, we investigate if earlier exposure to N2B27 could improve embryo development after hatching. Embryo culture in N2B27 from day (D) 5, 6 or 7 significantly enhanced complete hypoblast migration (>45 vs. â¼24%) and epiblast development into an embryonic disc (ED)-like structure at D12 (>40 vs. 23%), compared to embryos cultured in SOF up to D9. Culture in N2B27 from D5 significantly increased epiblast and hypoblast cell number in D8 blastocysts, but post-hatching embryos cultured in N2B27 from D5 or 6 frequently showed a disorganized distribution of epiblast cells. In conclusion, bovine embryo culture in N2B27 from D7 onwards improves subsequent post-hatching development. This improved fully in vitro system will be very useful to functionally explore cell differentiation mechanisms and the bases of early pregnancy failures without requiring animal experimentation.
Assuntos
Aborto Animal , Doenças dos Bovinos , Gravidez , Feminino , Bovinos , Animais , Blastocisto/fisiologia , Embrião de Mamíferos , Parto , Diferenciação Celular , Desenvolvimento Embrionário/fisiologia , Técnicas de Cultura Embrionária/veterinária , Fertilização in vitro/veterináriaRESUMO
Climate change worsening due to global warming and progressive abandonment in rural areas mean that wildfires are increasing in extent and severity terms, and are one of the major disturbances in the Mediterranean Basin. To mitigate these disturbances, preventive management tools need to be used. Fire employment is being implemented, known as prescribed burnings, as forestry actions to change vegetation lines both vertically and horizontally to eliminate forest fuel load continuity. This study aimed to know the ecological effects of late prescribed burning treatments under mixed trees. Prescribed burns were carried out in October 2019 in the municipality of Ayna, Albacete (SE Spain). To assess the short-term (12-month) fire impact on soil, we measured soil respiration with a CO2 flow chamber and analyzed soil physico-chemical properties. We also used minidisc infiltrometers to analyze soil repellency and soil hydraulic conductivity over a 1-year monitoring period. In addition, we evaluated the effects on tree strata by performing chemical nature analyses of fallen needles in Pinus pinaster after prescribed burning. According to our initial hypotheses, the results did not show significant changes in any parameter evaluated during the study period. However, some variables were affected in the first 3 months, needlefall and in microbiological activity, such as variations in soil physico-chemical properties, which can be due to long dry seasons combined with prescribed burning. This study attempts to observe and make known the effects that low-intensity prescribed burning has on soil and needlefall, which are relevant for updating forest management tools.
Assuntos
Incêndios , Pinus , Solo/química , Florestas , Agricultura Florestal , ÁrvoresRESUMO
Antecedentes y objetivo Durante los últimos 15 años se han sucedido múltiples cambios en el tratamiento del cáncer de mama (CM) y, en especial, en las indicaciones de la biopsia del ganglio centinela (BGC) y las actitudes ante su resultado. Valorando estos avances, nuestro objetivo es comparar los resultados de las BGC realizadas en nuestro centro en 2012, año a partir del cual se dejó de practicar linfadenectomía axilar (LA) ante el hallazgo de micrometástasis en la BGC, con aquellas llevadas a cabo en 2018, cuando empezaron a aplicarse los criterios Z0011. Material y métodos Hemos desarrollado un estudio retrospectivo observacional comparativo entre la población de pacientes con CM cN0 a las que se les hizo una BGC en el año 2012 y aquellas a las que se les practicó este procedimiento en 2018. Resultados Al analizar los 2 grupos, 174 pacientes de 2012 y 165 de 2018, se hallaron algunas diferencias significativas: en 2018 hubo mayor tasa de BGC, menor número de cánceres lobulillares (14/28; p<0,05), el tamaño medio anatomopatológico fue menor (p<0,001), la representación de tumores Her2 y triple negativos fue mayor (28/49; p<0,01), así como la proporción de tratamiento neoadyuvante (6,6 vs. 42,5%; p<0,001). Al valorar los resultados del estudio axilar, en 2018 hubo un descenso tanto en la positividad de la BGC, que descendió a casi la mitad que en 2012 (42,4 vs. 24,1%; p<0,0001), como en el porcentaje de LA (21,2 vs. 12,6%; p<0,05), así como el de LA con resultado negativo (74,3 vs. 59,1%; p=ns). Conclusión En el grupo de estudio de 2018 se halló una mayor tasa de BGC, con menor tasa de resultado positivo y de LA en blanco, pese a tratarse de una población con tumores más agresivos. Este hecho podría justificarse con la mejora en el filtro radiológico mediante ecografía al diagnóstico, así como con el aumento en el uso de la terapia neoadyuvante (AU)
Background and objective Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for sentinel lymph node biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. Materials and methods We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. Results A total of 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the 2groups: in 2018 there were fewer lobular invasive cancers (14 vs. 28) (P<0.05), a smaller mean pathological size(P<0.001), a higher proportion of HER2 and triple negative tumors (28 vs. 49; P<0.01) and, finally, an increase in use of neoadjuvant treatments (42.0 vs. 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs. 42.4% in 2012; P<0.0001) as well as in the proportion of ALND performed (12.6% in 2018 vs. 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs. 74.3%; P=ns). Conclusion Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla (AU)
Assuntos
Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Linfonodos/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Vigilância de Evento Sentinela , Excisão de Linfonodo , Axila/patologiaRESUMO
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile (AU)
El manejo del carcinoma de células escamosas cutáneo (cSCC) avanzado es complicado, siendo modesta la eficacia de muchos de los fármacos sistémicos disponibles. Cemiplimab ha demostrado su eficacia en el tratamiento del cSCC avanzado en ensayos clínicos, pero los datos del mundo real siguen siendo limitados. Con el objetivo de evaluar la eficacia de cemiplimab en un entorno clínico del mundo real, realizamos un estudio observacional prospectivo de 13 pacientes con cSCC avanzado. Seis pacientes (46%) tenían enfermedad localmente avanzada, mientras que 7 (54%) tenían enfermedad metastásica. Un total de 8 pacientes (62%) respondieron a cemiplimab, 5 (38%) mostraron una respuesta parcial y 3 (23%) mostraron una respuesta completa. Cuatro pacientes con respuesta parcial inicial presentaron una progresión de la enfermedad subsiguiente durante el seguimiento. Seis pacientes (46%) desarrollaron efectos secundarios, siendo leve la mayoría de los mismos (G1). La supervivencia libre de progresión fue de 5,9 meses, con un seguimiento medio de 9 meses. En conclusión, cemiplimab demostró su utilidad en el tratamiento del cSCC avanzado, con unas tasas de respuesta aceptables, un número destacable de respuestas completas y un perfil de seguridad muy bueno (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Intervalo Livre de Progressão , Antineoplásicos Imunológicos , Estadiamento de Neoplasias , Seguimentos , Estudos ProspectivosRESUMO
El manejo del carcinoma de células escamosas cutáneo (cSCC) avanzado es complicado, siendo modesta la eficacia de muchos de los fármacos sistémicos disponibles. Cemiplimab ha demostrado su eficacia en el tratamiento del cSCC avanzado en ensayos clínicos, pero los datos del mundo real siguen siendo limitados. Con el objetivo de evaluar la eficacia de cemiplimab en un entorno clínico del mundo real, realizamos un estudio observacional prospectivo de 13 pacientes con cSCC avanzado. Seis pacientes (46%) tenían enfermedad localmente avanzada, mientras que 7 (54%) tenían enfermedad metastásica. Un total de 8 pacientes (62%) respondieron a cemiplimab, 5 (38%) mostraron una respuesta parcial y 3 (23%) mostraron una respuesta completa. Cuatro pacientes con respuesta parcial inicial presentaron una progresión de la enfermedad subsiguiente durante el seguimiento. Seis pacientes (46%) desarrollaron efectos secundarios, siendo leve la mayoría de los mismos (G1). La supervivencia libre de progresión fue de 5,9 meses, con un seguimiento medio de 9 meses. En conclusión, cemiplimab demostró su utilidad en el tratamiento del cSCC avanzado, con unas tasas de respuesta aceptables, un número destacable de respuestas completas y un perfil de seguridad muy bueno (AU)
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Intervalo Livre de Progressão , Antineoplásicos Imunológicos , Estadiamento de Neoplasias , Seguimentos , Estudos ProspectivosRESUMO
Forest fires intensify sediment transport and aggravate local and off-site consequences of soil erosion. This study evaluates the influence of post-fire measures on structural and functional sediment connectivity (SC) in five fire-affected Mediterranean catchments, which include 929 sub-catchments, by using the "aggregated index of connectivity" (AIC) at two temporal scenarios: I) immediately after the fire and before implementing post-fire practices ('Pre-man'), and II) two years after the fire ('Post-man'). The latter includes all the emergency stabilization practices, that are hillslope barriers, check-dams and afforestation. The stream system was set as the target of the computation (STR), to be representative of intense rainfall-runoff events with effective sediment delivery outside the catchments. Output normalization (AICN) allows comparing the results of the five basins between them. The sedimentological analysis is based on specific sediment yield (SSY) -measured at the check-dams installed after the fire -, and this data is used for output evaluation. Stream density and slope variables were the most influential factors on AICN-STR results at the sub-catchment scale. Post-fire hillslope treatments (barriers when built in high densities and afforestation) significantly reduced AICN-STR in comparison with untreated areas in both structural and functional approaches. Despite the presence of hillslope treatments, the higher erosive rainfall conditions resulted in higher AICN-STR values in the Post-man scenario (functional approach). A positive and good correlation was found between the measured SSY and the AICN-STR changes due to the post-fire practices and vegetation recovery, showing the good correspondence of the computation results and the real sediment dynamics of the studied catchments. Overall, AICN demonstrated to be a useful and versatile tool for post-fire management, which needs further research to optimize its applicability.
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Incêndios , Rios , Ecossistema , Florestas , Humanos , SoloRESUMO
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Imunoterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Management of advanced cSCC is challenging, and many available systemic medications have modest efficacy. Cemiplimab has demonstrated efficacy in the treatment of advanced cSCC in clinical trials, but real-world data are still limited. With the objective of evaluating the efficacy of cemiplimab in a real-world clinical setting, we conducted a prospective observational study of 13 patients with advanced cSCC. Six patients (46%) had locally advanced disease, while 7 (54%) had metastatic disease. A total of 8 patients (62%) responded to cemiplimab. Five (38%) showed a partial response, while 3 (23%) showed a complete response. Four patients with an initial partial response presented subsequent disease progression during follow-up. Six patients (46%) developed AEs, most of which were mild (G1). PFS was 5.9 months, with a median follow-up was 9 months. In conclusion, cemiplimab demonstrated its utility in the treatment of advanced cSCC, with acceptable response rates, a remarkable number of complete responses, and a very good safety profile.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Imunoterapia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND AND OBJECTIVE: Over the last 15 years, breast cancer (BC) treatment has undergone numerous changes, which have also affected the indications for Sentinel Lymph Node Biopsy (SLNB) as well as the procedures depending on its outcome. The aim of this study is to compare the results of the SLNB carried out at our Center during 2012, when we stopped performing an axillary lymph node dissection (ALND) after the finding of a micrometastasis, with those conducted in 2018, when we started applying Z011 criteria. MATERIALS AND METHODS: We have performed a comparative retrospective observational study, including cN0 BC patients that underwent a SLNB in 2012 versus those that underwent this procedure in 2018. RESULTS: 174 patients from 2012 and 165 from 2018 were studied. We found significant differences between the two groups: in 2018 there were fewer lobular invasive cancers (14 vs 28) (Pâ¯<â¯.05), a smaller mean pathological size (Pâ¯<â¯.001), a higher proportion of HER2 and triple negative tumors (28 vs 49) (Pâ¯<â¯.01) and, finally, an increase in use of neoadjuvant treatments (42.0% vs 6.7%). Regarding axillary involvement, we observed a decrease in both the presence of a positive sentinel node (24.1% in 2018 vs 42.4% in 2012) (Pâ¯<â¯.0001) as well as in the proportion of ALND performed (12.6% in 2018 vs 21.2% in 2012) and the presence of positive non sentinel nodes after a ALND (59.1% vs74.3%) (ns) CONCLUSION: Although the 2018 cohort that underwent SLNB had more aggressive tumors, there were fewer positive SN and ALND performed. This is probably due to a more accurate radiological diagnosis with ultrasound, that enables to detect cN1 cases before surgery, and to the increasing use of neoadjuvant treatments that may downstage the axilla.