RESUMEN
BACKGROUND: Confusion exists regarding interstitial granulomatous dermatitis (IGD) and palisaded neutrophilic and granulomatous dermatitis (PNGD). OBJECTIVE: To determine whether IGD and PNGD are two different entities, or whether they must be considered as two subtypes of the same reactive pattern, and thus whether the unification of the nomenclature is necessary. METHODS: Observational retrospective multicentre study of patients with IGD and PNGD evaluated between 1999 and 2019 and review of their clinical and histological features. RESULTS: We identified 52 patients (38 women and 14 men). Clinical and histological findings of IGD were observed in 88.4% of cases. The most common cutaneous lesions were plaques/macules (IGD) or annular plaques and papules/nodules (PNGD), located mostly on the limbs and trunk. The rope sign was developed in two patients with IGD that associated autoimmune disorders. Similar associated comorbidities (75%) were found in both entities, mainly autoimmune diseases (53.8%). In IGD, the infiltrate was predominantly lympho-histiocytic. Neutrophilic infiltrates, karyorrhexis and skin lesions with limited clinical course were mainly associated with PNGD biopsies. In biopsies with a limited recurrent course, a predominant lymphocytic inflammatory infiltrate was found. Collagen degeneration was present in 75.9% of cases. The floating sign was observed only in IGD type patients (63%). Overlapping histological findings were found in one fourth of cases, especially between IGD and interstitial granuloma annulare. Interface dermatitis, apparently unrelated to drug intake, was observed in 4 cases of IGD. CONCLUSION: We support the term reactive granulomatous dermatitis to unify both the clinical and histological findings of IGD and PNGD, and the overlapping between IGD and interstitial granuloma annulare. According to this, a spectrum of histological changes will be found depending on the clinical course of the skin lesions.
Asunto(s)
Enfermedades Autoinmunes , Dermatitis , Femenino , Granuloma , Humanos , Masculino , Neutrófilos , Estudios RetrospectivosRESUMEN
No disponible
Asunto(s)
Humanos , Femenino , Anciano de 80 o más Años , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Penfigoide Benigno de la Membrana Mucosa/etiología , Estenosis Esofágica/diagnóstico , Estenosis Esofágica/patología , Gingivitis/complicaciones , Vulva/patología , Enfermedades de la Vulva/diagnóstico , Biopsia , Técnica del Anticuerpo Fluorescente Directa/métodos , Prednisona/administración & dosificación , Tacrolimus/administración & dosificación , Endoscopía del Sistema Digestivo/métodos , Penfigoide Benigno de la Membrana Mucosa/terapiaAsunto(s)
Pénfigo Familiar Benigno/tratamiento farmacológico , Pénfigo Familiar Benigno/patología , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Talidomida/análogos & derivados , Adulto , Enfermedad Crónica , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pénfigo Familiar Benigno/genética , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Calidad de Vida , Índice de Severidad de la Enfermedad , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.
Asunto(s)
Reparación de la Incompatibilidad de ADN , Proteínas de Unión al ADN/metabolismo , Mesotelioma Maligno/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pleurales/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunohistoquímica , Inmunoterapia , Masculino , Mesotelioma Maligno/genética , Mesotelioma Maligno/mortalidad , Mesotelioma Maligno/terapia , Inestabilidad de Microsatélites , Persona de Mediana Edad , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Homólogo 1 de la Proteína MutL/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Neoplasias Pleurales/genética , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/terapia , Estudios Retrospectivos , Análisis de SupervivenciaAsunto(s)
Síndromes Paraneoplásicos , Pénfigo , Anticuerpos , Humanos , Pénfigo/tratamiento farmacológicoAsunto(s)
Ciclosporina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Síndrome de Stevens-Johnson/tratamiento farmacológico , Ciclosporina/administración & dosificación , Fármacos Dermatológicos/administración & dosificación , Humanos , Metaanálisis como Asunto , Estudios Prospectivos , Estudios Retrospectivos , Síndrome de Stevens-Johnson/mortalidadAsunto(s)
Autoanticuerpos/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Epítopos/efectos de los fármacos , Hipoglucemiantes/efectos adversos , Penfigoide Ampolloso/inmunología , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Epítopos/inmunología , Femenino , Humanos , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/inducido químicamente , Colágeno Tipo XVIIRESUMEN
Atmospheric iodine plays a relevant role in climate change. Bearing in mind that most of this iodine comes from the oceans, analytical methods capable of determining iodine in a challenging matrix as seawater are necessary. In this work, the first method capable of direct determination of total inorganic iodine in seawater at subnanomolar level based on mixed-mode liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) without any sample treatment is presented. Analytical characteristics of the developed method were studied in terms of linear range, limits of detection and quantification, precision, trueness, matrix effect, and robustness. The detection limit for iodide was as low as 0.16 nM, injecting 5 µL of seawater without any sample treatment and the working linear range of four orders of magnitude was wide enough to cover the broad concentration range observed in seawater samples. Average values for repeatability and intermediate precision were 4.1% and 8.1%, respectively. The suitability of the method was demonstrated through its application to the analysis of several types of samples, including seawater samples taken at different locations along the Spanish Mediterranean coast and some domestic iodized salts. According to the results obtained, the method developed is rapid, easy to apply and to be automated, avoids sample treatment and requires only few microliters of sample. Furthermore, it has a low detection limit and allows the quantification of inorganic iodine over a wide concentration range.
Asunto(s)
Cromatografía Liquida , Monitoreo del Ambiente/métodos , Yodo/análisis , Agua de Mar/química , Espectrometría de Masa por Ionización de Electrospray , Límite de DetecciónRESUMEN
BACKGROUND: Approximately 30% of tumor biopsies from patients with advanced-stage lung adenocarcinomas yield insufficient tissue for successful molecular subtyping. We have analyzed the clinical utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) in patients with inadequate tumor samples for tissue genotyping. PATIENTS AND METHODS: We conducted the study in a multi-institutional prospective cohort of clinically unselected patients with advanced-stage lung adenocarcinomas with insufficient tissue for EGFR, ALK or ROS1 genotyping across 12 Spanish institutions (n = 93). ctDNA NGS was carried out by Guardant Health (Guardant360, Redwood City, CA), using a hybrid-capture-based 73-gene panel. Variants were deemed actionable if they were part of the OncoKB precision oncology knowledge database and classified in four levels of actionability based on their clinical or preclinical evidence for drug response. RESULTS: Eighty-three out of 93 patients (89%) had detectable levels of ctDNA. Potentially actionable level 1-4 genomic alterations were detected in 53 cases (57%), of which 13 (14%) had level 1-2A alterations (Food and Drug Administration-approved and standard-care biomarkers according to lung cancer guidelines). Frequencies of each genomic alteration in ctDNA were consistent with those observed in unselected pulmonary adenocarcinomas. The majority of the patients (62%), particularly those with actionable alterations (87%), had more than one pathogenic variant in ctDNA. The median turnaround time to genomic results was 13 days. Twelve patients (13%) received genotype-matched therapies based on ctDNA results, deriving the expected clinical benefit. Patients with co-occurring pathogenic alterations had a significantly shorter median overall survival as compared with patients without co-occurring pathogenic alteration (multivariate hazard ratio = 5.35, P = 0.01). CONCLUSION: Digital NGS of ctDNA in lung cancers with insufficient tumor samples for tissue sequencing detects actionable variants that frequently co-occur with other potentially clinically relevant genomic alterations, allowing timely initiation of genotype-matched therapies.
Asunto(s)
Adenocarcinoma del Pulmón/secundario , Biomarcadores de Tumor/sangre , ADN Tumoral Circulante/sangre , ADN de Neoplasias/sangre , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neoplasias Pulmonares/patología , Proteínas Proto-Oncogénicas/genética , Adenocarcinoma del Pulmón/sangre , Adenocarcinoma del Pulmón/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , ADN de Neoplasias/genética , Femenino , Estudios de Seguimiento , Genoma Humano , Genómica , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Medicina de Precisión , Pronóstico , Estudios Prospectivos , Tasa de SupervivenciaRESUMEN
No disponible
Asunto(s)
Humanos , Dermatitis Atópica/tratamiento farmacológico , Prurito/tratamiento farmacológico , Factores de Tiempo , Descubrimiento de DrogasRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Anciano , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/tratamiento farmacológico , Síndrome de Churg-Strauss/etiología , Cuero Cabelludo/lesiones , Síndrome de Churg-Strauss/patología , Síndrome de Churg-Strauss/prevención & controlRESUMEN
No disponible
