RESUMEN
OBJECTIVES: The Node-RADS score was recently introduced to offer a standardized assessment of lymph node invasion (LNI). We tested its diagnostic performance in accurately predicting LNI in breast cancer (BC) patients with magnetic resonance imaging. The study also explores the consistency of the score across three readers. MATERIALS AND METHODS: A retrospective study was conducted on BC patients who underwent preoperative breast contrast-enhanced magnetic resonance imaging and lymph node dissection between January 2020 and January 2023. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for different Node-RADS cut-off values. Pathologic results were considered the gold standard. The overall diagnostic performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). A logistic regression analysis was performed. Cohen's Kappa analysis was used for inter-reader agreement. RESULTS: The final population includes 192 patients and a total of 1134 lymph nodes analyzed (372 metastatic and 762 benign). Increasing the Node-RADS cut-off values, specificity and PPV rose from 71.4% to 100% and 76.7% to 100%, respectively, for Reader 1, 69.4% to 100% and 74.6% to 100% for Reader 2, and from 64.3% to 100% and 72% to 100% for Reader 3. Node-RADS > 2 could be considered the best cut-off value due to its balanced performance. Node-RADS exhibited a similar AUC for the three readers (0.97, 0.93, and 0.93). An excellent inter-reader agreement was found (Kappa values between 0.71 and 0.83). CONCLUSIONS: The Node-RADS score demonstrated moderate-to-high overall accuracy in identifying LNI in patients with BC, suggesting that the scoring system can aid in the identification of suspicious lymph nodes and facilitate appropriate treatment decisions. CLINICAL RELEVANCE STATEMENT: Node-RADS > 2 can be considered the best cut-off for discriminating malignant nodes, suggesting that the scoring system can effectively help identify suspicious lymph nodes by staging the disease and providing a global standardized language for clear communication. KEY POINTS: Axillary lymphadenopathies in breast cancer are crucial for determining the disease stage. Node-RADS was introduced to provide a standardized evaluation of breast cancer lymph nodes. RADS > 2 can be considered the best cut-off for discriminating malignant nodes.
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Distinct outcomes of BRAF inhibition in BRAF-mutated hairy cell neoplasms with wild-type or mutant TP53, and alternative strategies to overcome mutant TP53.
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Neoplasias , Proteínas Proto-Oncogénicas B-raf , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Medicina de Precisión , MutaciónRESUMEN
Cryoablation is a minimally invasive technique currently employed in breast cancer care, that uses freeze and thaw cycles to treat benign breast lesions, small breast cancers or focal sites of metastatic disease in patients not eligible for surgery. The final goal of this procedure is to destroy breast cancer cells using extreme cold. In addition, several studies have shown that this technique seems to have an enhancing effect on the immune response, especially by increasing the expression of tumor neoantigens specific to tumor cells, which are then attacked and destroyed. Exploiting this effect, cryoablation in combination with immunotherapy could be the key to treating early-stage breast cancers or patients who are unsuitable for surgery. According to some recent studies, there are other potential tools that could be used to enhance the therapeutic effect of cryoablation, such as FE3O4 nanoparticles or the manipulation of aquaporin expression. The aim of this narrative review is to summarize the current evidence regarding the use, indications, advantages and disadvantages of cryoablation in the treatment of breast cancer.
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Neoplasias de la Mama , Criocirugía , Humanos , Femenino , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Criocirugía/métodos , UtopiasRESUMEN
The treatment of acute myeloid leukemia (AML) with adverse genetics remains unsatisfactory, with very low response rates to standard chemotherapy and shorter durations of remission commonly observed in these patients. The complex biology of AML with adverse genetics is continuously evolving. Herein, we discuss recent advances in the field focusing on the contribution of molecular drivers of leukemia biogenesis and evolution and on the alterations of the immune system that can be exploited with immune-based therapeutic strategies. We focus on the biological rationales for combining targeted therapy and immunotherapy, which are currently being investigated in ongoing trials, and could hopefully ameliorate the poor outcomes of patients affected by AML with adverse genetics.
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Leucemia Mieloide Aguda , Medicina de Precisión , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Medicina de Precisión/métodos , Inmunoterapia/métodos , Terapia Molecular Dirigida/métodosRESUMEN
Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.
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Fibroblastos Asociados al Cáncer , Cisplatino , Interleucina-6 , Mesotelioma Maligno , Organoides , Pemetrexed , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/farmacología , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/efectos de los fármacos , Fibroblastos Asociados al Cáncer/patología , Cisplatino/farmacología , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Interleucina-6/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mesotelioma/patología , Mesotelioma/tratamiento farmacológico , Mesotelioma/metabolismo , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma Maligno/patología , Mesotelioma Maligno/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Organoides/metabolismo , Organoides/efectos de los fármacos , Organoides/patología , Pemetrexed/farmacología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Key features of chronic lymphocytic leukemia (CLL) are defects in the immune system and the ability of leukemic cells to evade immune defenses and induce immunosuppression, resulting in increased susceptibility to infections and disease progression. Several immune effectors are impaired in CLL, including T and natural killer (NK) cells. The role of T cells in defense against CLL and in CLL progression and immunotherapy has been extensively studied. Less is known about the role of NK cells in this leukemia, and data on NK cell alterations in CLL are contrasting. Besides studies showing that NK cells have intrinsic defects in CLL, there is a large body of evidence indicating that NK cell dysfunctions in CLL mainly depend on the escape mechanisms employed by leukemic cells. In keeping, it has been shown that NK cell functions, including antibody-dependent cellular cytotoxicity (ADCC), can be retained and/or restored after adequate stimulation. Therefore, due to their preserved ADCC function and the reversibility of CLL-related dysfunctions, NK cells are an attractive source for novel immunotherapeutic strategies in this disease, including chimeric antigen receptor (CAR) therapy. Recently, satisfying clinical responses have been obtained in CLL patients using cord blood-derived CAR-NK cells, opening new possibilities for further exploring NK cells in the immunotherapy of CLL. However, notwithstanding the promising results of this clinical trial, more evidence is needed to fully understand whether and in which CLL cases NK cell-based immunotherapy may represent a valid, alternative/additional therapeutic option for this leukemia. In this review, we provide an overview of the current knowledge about phenotypic and functional alterations of NK cells in CLL and the mechanisms by which CLL cells circumvent NK cell-mediated immunosurveillance. Additionally, we discuss the potential relevance of using NK cells in CLL immunotherapy.
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Susceptibilidad a Enfermedades , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Leucemia Linfocítica Crónica de Células B/etiología , Leucemia Linfocítica Crónica de Células B/metabolismo , Biomarcadores , Comunicación Celular , Manejo de la Enfermedad , Humanos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/terapia , Ligandos , Unión Proteica , Receptores de Células Asesinas Naturales/genética , Receptores de Células Asesinas Naturales/metabolismo , Resultado del Tratamiento , Escape del Tumor/genética , Escape del Tumor/inmunologíaRESUMEN
BACKGROUND: Ibezapolstat (ACX-362E) is the first DNA polymerase IIIC inhibitor undergoing clinical development for the oral treatment of Clostridioides difficile infection (CDI). METHODS: In this study, the in vitro activity of ibezapolstat was evaluated against a panel of 104 isolates of C. difficile, including those with characterized ribotypes (e.g. 027 and 078) and those producing toxin A or B and was shown to have similar activity to those of comparators against these strains. RESULTS: The overall MIC50/90 (mg/L) for ibezapolstat against evaluated C. difficile was 2/4, compared with 0.5/4 for metronidazole, 1/4 for vancomycin and 0.5/2 for fidaxomicin. In addition, the bactericidal activity of ibezapolstat was evaluated against actively growing C. difficile by determining the MBC against three C. difficile isolates. Time-kill kinetic assays were additionally performed against the three C. difficile isolates, with metronidazole and vancomycin as comparators. CONCLUSIONS: The killing of C. difficile by ibezapolstat was observed to occur at concentrations similar to its MIC, as demonstrated by MBC:MIC ratios and reflected in time-kill kinetic assays. This activity highlights the therapeutic potential of ibezapolstat for the treatment of CDI.
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Clostridioides difficile , Infecciones por Clostridium , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Clostridioides , Infecciones por Clostridium/tratamiento farmacológico , Fidaxomicina , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
BACKGROUND: Omadacycline, an aminomethylcycline, was approved in 2018 for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. In a Phase Ib study, around 34% of the absorbed dose of omadacycline was shown to be excreted in urine-an important property for urinary tract infection (UTI) treatment. Therefore, omadacycline has been studied in two Phase II trials for the treatment of uncomplicated UTIs and acute pyelonephritis. The activity of omadacycline against UTI pathogens in human urine is important to understand in this context. OBJECTIVES: To study the in vitro activity of omadacycline against UTI pathogens in human urine supplemented with calcium and magnesium. METHODS: Omadacycline activity was compared with that of levofloxacin against the urinary pathogens Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus in standard medium, pooled normal human urine and neutral pH-adjusted pooled normal human urine spiked with calcium or magnesium at concentrations consistent with hypercalcaemia and hypermagnesaemia. RESULTS: The activities of omadacycline and levofloxacin against these urinary pathogens were lower in urine relative to standard medium; addition of Mg2+ to broth and urine had a further negative impact on omadacycline activity, whereas the addition of Ca2+ had less of an impact. Levofloxacin activity was not substantially reduced in either broth or urine by the addition of divalent cations. CONCLUSIONS: The activity of omadacycline against UTI organisms was lower in urine relative to standard medium and was negatively impacted by magnesium. Omadacycline displayed slightly reduced activity when excess calcium was present, but, overall, the differences were ≤2-fold. These observations should be considered along with the pharmacokinetics of the agent for clinical context.
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Magnesio , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Calcio , Escherichia coli , Humanos , Klebsiella pneumoniae , Levofloxacino , Pruebas de Sensibilidad Microbiana , Staphylococcus saprophyticus , Tetraciclinas , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
Omadacycline (OMC), a broad-spectrum aminomethylcycline, has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections. Here, the in vitro activity of OMC against clinically relevant anaerobes was similar to that of tigecycline, with MIC90 values of 1 to 8 µg/ml against Bacteroides spp., 0.5 µg/ml against Clostridium difficile, Prevotella spp., and Porphyromonas asaccharolytica, 1 µg/ml against Peptostreptococcus spp., and 16 µg/ml against Clostridium perfringens.
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Antibacterianos/farmacología , Bacterias Anaerobias/efectos de los fármacos , Tetraciclinas/farmacología , Clostridioides difficile/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Peptostreptococcus/efectos de los fármacos , Porphyromonas/efectos de los fármacos , Prevotella/efectos de los fármacos , Tigeciclina/farmacologíaRESUMEN
BACKGROUND: Functional assessment of non-infarct-related artery lesions during primary percutaneous coronary intervention (PCI) might be useful to avoid revascularization of nonsignificant stenosis and staged procedures, thus reducing hospital stay. We aimed to assess the diagnostic performance of instantaneous wave-free ratio (iFR) as compared with fractional flow reserve (FFR) in this setting. METHODS: In the WAVE study, a prospective, observational, single-center registry (NCT02869906), paired iFR and FFR measurements were performed at the level of non-IRA lesions in patients with ST-segment elevation myocardial infarction both during primary PCI and during staged procedures (5-8 days after). RESULTS: Paired iFR and FFR measurements were available for 66 non-IRA lesions in 50 patients. The iFR and FFR values of non-IRA lesions did not change significantly between the index and staged procedure. Bland-Altman analysis did not show systematic bias for either iFR or FFR repeated measures. Receiver operating characteristic curve analysis showed high accuracy of iFR to identify positive (≤0.80) FFR measurements in the index procedure with an area under the curve of 0.95. A cutoff of ≤0.89 for iFR in the index procedure had the best combination of sensitivity (95%) and specificity (90%) with positive and negative predictive values of 86% and 97%, respectively. Finally, iFR measured during the index procedure was significantly correlated with FFR (r=0.71, r2=0.51; P<.0001). CONCLUSIONS: The WAVE study shows that iFR yields similar diagnostic accuracy to FFR in functional evaluation of non-IRA stenosis in patients with STEMI and multivessel CAD, with the advantage of being adenosine free.
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Vasos Coronarios/diagnóstico por imagen , Reserva del Flujo Fraccional Miocárdico/fisiología , Infarto del Miocardio con Elevación del ST/fisiopatología , Anciano , Angiografía por Tomografía Computarizada , Angiografía Coronaria , Vasos Coronarios/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Revascularización Miocárdica , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugíaAsunto(s)
Leucemia Mieloide Aguda/patología , Placenta/patología , Complicaciones Neoplásicas del Embarazo/patología , Sarcoma Mieloide/patología , Adulto , Femenino , Humanos , Recién Nacido , Leucemia Mieloide Aguda/genética , Embarazo , Complicaciones Neoplásicas del Embarazo/genética , Sarcoma Mieloide/genéticaAsunto(s)
Transformación Celular Neoplásica/patología , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/patología , Miocardio/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Procedimientos Quirúrgicos Cardíacos , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Diagnóstico Diferencial , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/terapia , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/terapia , Miocardio/inmunología , Valor Predictivo de las Pruebas , Resultado del TratamientoAsunto(s)
Hematopoyesis/genética , Leucemia Mieloide Aguda/genética , Linfoma de Células T/genética , Mutación , Neoplasias Primarias Secundarias/genética , Proteínas Nucleares/genética , Humanos , Linfadenopatía Inmunoblástica/genética , Leucemia Mieloide Aguda/patología , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , NucleofosminaAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Sarcoma , Neoplasias Uterinas , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Resultado Fatal , Femenino , Humanos , Persona de Mediana Edad , Sarcoma/tratamiento farmacológico , Sarcoma/metabolismo , Sarcoma/patología , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologíaAsunto(s)
Inmunoglobulina A/análisis , Mutación Missense , Factor 88 de Diferenciación Mieloide/genética , Paraproteínas/análisis , Mutación Puntual , Macroglobulinemia de Waldenström/diagnóstico , Anciano , Linfocitos B/inmunología , Linfocitos B/patología , Médula Ósea/patología , Análisis Mutacional de ADN , Humanos , Cadenas kappa de Inmunoglobulina/análisis , Masculino , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Macroglobulinemia de Waldenström/complicaciones , Macroglobulinemia de Waldenström/genética , Macroglobulinemia de Waldenström/inmunologíaAsunto(s)
Neoplasias Óseas/diagnóstico , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Sarcoma de Ewing/diagnóstico , Sarcoma Mieloide/diagnóstico , Aloinjertos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Terapia Combinada , Diagnóstico Diferencial , Resultado Fatal , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Nucleofosmina , Terapia Recuperativa , Sarcoma Mieloide/genética , Sarcoma Mieloide/patología , Sarcoma Mieloide/terapia , Adulto JovenRESUMEN
It is increasingly clear that Intratumor heterogeneity (ITH) fuels tumor evolution, matching the concept of cancer as a heterogeneous ecosystem of spatially and temporally modulated cell subpopulations, which exploits dynamic strategies to hijack local and systemic resources and tissue(s) space [...].