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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Radiofármacos , Rabdomiosarcoma , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Rabdomiosarcoma/diagnóstico por imagen , NiñoRESUMEN
BACKGROUND: Globally, many undescribed fungal taxa reside in the hyperdiverse, yet undersampled, tropics. These species are under increasing threat from habitat destruction by expanding extractive industry, in addition to global climate change and other threats. Reserva Los Cedros is a primary cloud forest reserve of ~ 5256 ha, and is among the last unlogged watersheds on the western slope of the Ecuadorian Andes. No major fungal survey has been done there, presenting an opportunity to document fungi in primary forest in an underrepresented habitat and location. Above-ground surveys from 2008 to 2019 resulted in 1760 vouchered collections, cataloged and deposited at QCNE in Ecuador, mostly Agaricales sensu lato and Xylariales. We document diversity using a combination of ITS barcode sequencing and digital photography, and share the information via public repositories (GenBank & iNaturalist). RESULTS: Preliminary identifications indicate the presence of at least 727 unique fungal species within the Reserve, representing 4 phyla, 17 classes, 40 orders, 101 families, and 229 genera. Two taxa at Los Cedros have recently been recommended to the IUCN Fungal Red List Initiative (Thamnomyces chocöensis Læssøe and "Lactocollybia" aurantiaca Singer), and we add occurrence data for two others already under consideration (Hygrocybe aphylla Læssøe & Boertm. and Lamelloporus americanus Ryvarden). CONCLUSIONS: Plants and animals are known to exhibit exceptionally high diversity and endemism in the Chocó bioregion, as the fungi do as well. Our collections contribute to understanding this important driver of biodiversity in the Neotropics, as well as illustrating the importance and utility of such data to conservation efforts. RESUMEN: Antecedentes: A nivel mundial muchos taxones fúngicos no descritos residen en los trópicos hiper diversos aunque continúan submuestreados. Estas especies están cada vez más amenazadas por la destrucción del hábitat debido a la expansión de la industria extractivista además del cambio climático global y otras amenazas. Los Cedros es una reserva de bosque nublado primario de ~ 5256 ha y se encuentra entre las últimas cuencas hidrográficas no explotadas en la vertiente occidental de los Andes ecuatorianos. Nunca antes se ha realizado un estudio de diversidad micológica en el sitio, lo que significa una oportunidad para documentar hongos en el bosque primario, en hábitat y ubicación subrepresentatadas. El presente estudio recopila información entre el 2008 y 2019 muestreando material sobre todos los sustratos, reportando 1760 colecciones catalogadas y depositadas en el Fungario del QCNE de Ecuador, en su mayoría Agaricales sensu lato y Xylariales; además se documenta la diversidad mediante secuenciación de códigos de barras ITS y fotografía digital, la información está disponible en repositorios públicos digitales (GenBank e iNaturalist). RESULTADOS: La identificación preliminar indica la presencia de al menos 727 especies únicas de hongos dentro de la Reserva, que representan 4 filos, 17 clases, 40 órdenes, 101 familias y 229 géneros. Recientemente dos taxones en Los Cedros se recomendaron a la Iniciativa de Lista Roja de Hongos de la UICN (Thamnomyces chocöensis Læssøe y "Lactocollybia" aurantiaca Singer) y agregamos datos de presencia de otros dos que ya estaban bajo consideración (Hygrocybe aphylla Læssøe & Boertm. y Lamelloporus americanus Ryvarden). CONCLUSIONES: Se sabe que plantas y animales exhiben una diversidad y endemismo excepcionalmente altos en la bioregión del Chocó y los hongos no son la excepción. Nuestras colecciones contribuyen a comprender este importante promotor de la biodiversidad en el Neotrópico además de ilustrar la importancia y utilidad de dichos datos para los esfuerzos de conservación.
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Precise regulation of transcription in gene expression is critical for all aspects of normal organism form, fitness, and function and even minor alterations in the level, location, and timing of gene expression can result in phenotypic variation within and between species including evolutionary innovations and human disease states. Eukaryotic transcription is regulated by a complex interplay of multiple factors working both at a physical and molecular levels influencing this process. In Saccharomyces cerevisiae, the TF with the greatest number of putative regulatory targets is the essential gene Repressor Activator Protein 1 (RAP1). While much is known about the roles of Rap1 in gene regulation and numerous cellular processes, the response of Rap1 target genes to systematic titration of RAP1 expression level remains unknown. To fill this knowledge gap, we used a strain with a tetracycline-titratable promoter replacing wild-type regulatory sequences of RAP1 to systematically reduce the expression level of RAP1 and followed this with RNA sequencing (RNA-seq) to measure genome-wide gene expression responses. Previous research indicated that Rap1 plays a significant regulatory role in particular groups of genes including telomere-proximal genes, homothallic mating (HM) loci, glycolytic genes, DNA repair genes, and ribosomal protein genes; therefore, we focused our analyses on these groups and downstream targets to determine how they respond to reductions in RAP1 expression level. Overall, despite being known as both an activator and as a repressor of its target genes, we found that Rap1 acts as an activator for more target genes than as a repressor. Additionally, we found that Rap1 functions as an activator of ribosomal protein genes and a repressor for HM loci genes consistent with predictions from the literature. Unexpectedly, we found that Rap1 functions as a repressor of glycolytic enzyme genes contrary to prior reports of it having the opposite effect. We also compared the expression of RAP1 to five different genes related to DNA repair pathway and found that decreasing RAP1 downregulated four of those five genes. Finally, we found no effect of RAP1 depletion on telomere-proximal genes despite its functioning to silence telomeric repeat-containing RNAs. Together our results enrich our understanding of this important transcriptional regulator.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/genética , Factor de Transcripción AP-1/genética , Proteínas de Saccharomyces cerevisiae/genética , Complejo Shelterina , Proteínas de Unión a Telómeros/genética , Proteínas de Unión a Telómeros/metabolismo , Proteínas Ribosómicas/genética , Expresión Génica , Regulación Fúngica de la Expresión Génica , Proteínas Fúngicas/genética , Factores de Transcripción/metabolismoRESUMEN
RATIONALE: Clozapine has proven to be superior to other antipsychotic drugs in the treatment of schizophrenia but is under-prescribed due to its potentially severe side effects. Clozapine-induced sialorrhea (CIS) is a frequent and extremely uncomfortable side effect, which remains understudied. OBJECTIVES: To examine the prevalence of diurnal and nocturnal CIS in a sample of patients treated with clozapine, and to evaluate its impact on quality of life. METHODS: We conducted a cross-sectional, observational study of 130 patients with schizophrenia spectrum disorders treated with clozapine. The prevalence of CIS was evaluated via specific sialorrhea scales. None of the patients included in the study was receiving a specific treatment for hypersalivation during the study period. Possible associations between sialorrhea and clinical and quality of life variables were analyzed. RESULTS: Of 130 subjects, 120 (92.3%) suffered from CIS. Eighty-one (62.31%) suffered from diurnal CIS, 115 (88.56%) from nocturnal CIS, and 85 (65.38%) suffered from both. Significant positive associations between quality of life and diurnal CIS (B = 0.417; p = 2.1e - 6, R2 = 0.156) and nocturnal CIS (B = 0.411; p = 7.7e - 6, R2 = 0.139) were detected. Thirty per cent of the subjects reported a moderate to severe negative impact of sialorrhea on their quality of life. CONCLUSIONS: The present study suggests that CIS is highly prevalent in patients with schizophrenia and has an important impact on quality of life in one-third of our sample. Therefore, the inclusion of a systematic evaluation and treatment of CIS in standard clinical practice is highly recommended. TRIAL REGISTRATION: Clinical Trials ( https://clinicaltrials.gov ) under reference NCT04197037.
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Antipsicóticos , Clozapina , Sialorrea , Humanos , Clozapina/efectos adversos , Sialorrea/inducido químicamente , Sialorrea/epidemiología , Sialorrea/tratamiento farmacológico , Prevalencia , Calidad de Vida , Estudios Transversales , Antipsicóticos/efectos adversosRESUMEN
Objetivo: Evaluar la utilización de las semillas radiactivas de yodo-125 (SRI-125) en la cirugía de mama o axila, en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante (QtNeo).Material y métodos: Estudio prospectivo, entre enero del 2016 y junio del 2020; 80 mujeres T1-3, N0-2, M0: 30 marcaje SRI-125 del tumor en mama, 36 tanto del tumor como del ganglio axilar positivo biopsiado, y 14 solo de axila. Edad: 54,7±11,4 años. Tamaño tumoral: 34,1±14,6mm. Tipo histológico: ductal infiltrante 90,0%. Subtipos moleculares: luminal-A 23,8%; luminal-B/HER2- 33,7%; luminal-B/HER2+ 18,8%; HER2+ 7,5%; triple negativo 16,2%.Resultados: De las 66 pacientes con marcaje SRI-125 del tumor (51 pre-QtNeo, 15 post-QtNeo), el 92,1% presentaba márgenes quirúrgicos libres, con un volumen de las piezas de 126,7±111,2 cm3. De las 5 reintervenciones, en 3 la ampliación fue positiva (una mastectomía).De las 50 pacientes N1 con marcaje SRI-125 (GM), 44 pre-QtNeo y 6 post-QtNeo, se identificó el GM en el 97,2%: negativo en 23, positivo en 26. En 45 se realizó biopsia selectiva del ganglio centinela y se identificó en el 93,3%: negativo en 26, positivo en 16. En un caso la SRI-125 no se colocó correctamente y tampoco se localizó GC por no migración.En el 61,9% de las pacientes el GM se encontraba entre el/los GC identificados en la cirugía. En 5 pacientes, con GC y GM no coincidentes, el resultado anatomopatológico del GC fue negativo y el GM positivo. En 53,8% de las pacientes se realizó linfadenectomía axilar. Conclusión: Las SRI-125 permiten realizar cirugía conservadora de la mama y mejorar la detección de enfermedad residual axilar, en pacientes tratadas con QtNeo (AU)
Objective: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC).Material and methods: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%.Results: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy).Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration.In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients.Conclusion: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC (AU)
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Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Radioisótopos de Yodo/administración & dosificación , Estudios Prospectivos , Quimioterapia Adyuvante , Resultado del Tratamiento , MastectomíaAsunto(s)
Xantogranuloma Necrobiótico , Paraproteinemias , Fluorodesoxiglucosa F18 , Humanos , Xantogranuloma Necrobiótico/complicaciones , Xantogranuloma Necrobiótico/diagnóstico por imagen , Paraproteinemias/complicaciones , Paraproteinemias/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7⯱â¯11.4 years. Tumor size: 34.1⯱â¯14.6â¯mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7⯱â¯111.2â¯cm3. Of the 5â¯s local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.
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Neoplasias de la Mama , Cirugía Asistida por Computador , Neoplasias de la Tiroides , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Mastectomía , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Neoplasias de la Tiroides/cirugíaRESUMEN
OBJECTIVE: To evaluate the use of radioactive iodine-125 seed (RIS) in breast and/or axillary surgery, in patients with breast cancer treated with neoadjuvant chemotherapy (NAC). MATERIAL AND METHODS: Prospective study between January 2016 and June 2020. 80 women T1-3,N0-2,M0: 30 RIS marking the breast tumor, 36 both the tumor and the biopsied positive axillary node, and 14 only the axilla. Age: 54.7±11.4 years. Tumor size: 34.1±14.6mm. Histological type: invasive ductal carcinoma 90.0%. Molecular subtypes: luminal-A 23.8%, luminal-B/HER2- 33.7%, luminal-B/HER2+ 18.8%, HER2+ 7.5%, basal-like 16,2%. RESULTS: Of the 66 patients with RIS marking of the tumor (51 pre-NAC, 15 post-NAC), 92.1% had tumor-free surgical margins, with a specimen volume of 126.7±111.2 cm3. Of the 5 second local excisions, in 3 the resection margin was involved (1 mastectomy). Of the 50 patients N1 with RIS marking (MLN), 44 pre-NAC and 6 post-NAC, MLN was identified in 97.2%: negative 23, positive 26. In 45/50 patients, sentinel node biopsy (SNB) was performed and it was identified in 93.3%: negative 26, positive 16. In 1 case RIS was not placed correctly and SNB was not identified due to non-migration. In 61.9% of the patients, MLN was among the SNB identified in the surgery. In 5 patients with mismatched SNB and MLN, the pathological result of the SNB was negative and the MLN was positive. Axillary lymph node dissection was performed in 53.8% of the patients. CONCLUSION: RIS allow to perform breast-conserving surgery and improve detection of residual axillary disease in patients treated with NAC.
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BACKGROUND: The risk benefit ratio has been clearly proven for a long time to be in favor of vaccination. However, the vaccine distrust is still increasing in the French population and vaccination coverage could be improved. There is a real need to increase confidence in vaccination. In this study, we interviewed heath care workers to collect their opinion concerning vaccination hesitancy amongst their patients. METHODS: A qualitative study, using semi structured interviews, was performed. All the Pharmacists and doctors were interviewed by the same person using an interview guide prepared by a multidisciplinary team. Interviews were recorded and transcribed verbatim, then used as a basis for analysis and synthesis of the areas where improvement seems possible for the health care workers interviewed. RESULTS: Data saturation was obtained after 10 interviews. Analysis of the verbatim allowed the classification of the leads proposed by health care workers in three main themes: improvement of transparency and restoration of the trust for vaccine policy, improved initial and further training of health care workers, and a better communication towards the population. CONCLUSION: Results provide helpful insights into practical avenues to improve the vaccination confidence. If some of them need an in-depth reflection, others could be easily implemented in order to increase the adhesion of the population to vaccination, and consequently the vaccination coverage.
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Personal de Salud , Cobertura de Vacunación , Vacunación/estadística & datos numéricos , Adulto , Actitud del Personal de Salud , Comunicación , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Grupo de Atención al Paciente , Farmacéuticos , Médicos , Encuestas y CuestionariosRESUMEN
BACKGROUND: In France, many parents have lost confidence in vaccinations, which has a direct impact on immunization coverage. Pharmacists, like other health professionals, often encounter parents exhibiting vaccine distrust. METHODS: Using a survey distributed in a school and in a number of volunteering pharmacies, the objective of this study was to gain a better understanding of the views and the attitude of parents in regard to vaccination of their children. RESULTS: Our results show that the main concerns were in regard to vaccine adjuvants, the risk of short- and long-term adverse effects, and the risk of developing a disease or a disability as a result of vaccination. The parents, although they tended to express a degree of reluctance and apprehension, in general, they were not opposed to vaccination, and they sought objective scientific information and full transparency regarding all aspects of vaccine composition, adverse effects, and effectiveness. Cooperation of all the parties involved in the health system on this subject is essential for a seamless chain of care and to improve vaccination coverage. CONCLUSION: The information collected, combined with a review of the international literature, allow avenues for dialogue adapted to parents' opinions to be established and thus assist health professionals to communicate effectively regarding vaccines, which is a bona fide public health issue.
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Actitud , Padres , Vacunación/psicología , Adyuvantes Inmunológicos/efectos adversos , Adulto , Niño , Miedo , Femenino , Francia , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Aceptación de la Atención de Salud , Encuestas y Cuestionarios , Resultado del Tratamiento , Negativa del Paciente al Tratamiento , Vacunación/efectos adversos , Vacunas/efectos adversosRESUMEN
OBJECTIVE: Staphylococcusaureus is involved in around 20% of nosocomial pneumonia cases. Vancomycin used to be the reference antibiotic in this indication, but new molecules have been commercialized, such as linezolid. Previous studies comparing vancomycin and linezolid were based on models. Comparing their real costs from a hospital perspective was needed. METHODS: We performed a bicentric retrospective analysis with a cost-minimization analysis. The hospital antibiotic acquisition costs were used, as well as the laboratory test and administration costs from the health insurance cost scale. The cost of each hospital stay was evaluated using the national cost scale per diagnosis related group (DRG), and was then weighted by the stay duration. RESULTS: Fifty-eight patients were included. All bacteria identified in pulmonary samples were S. aureus. The cost of nursing care per stay with linezolid was 234.10 (SD=91.50) vs. 381.70 (SD=184.70) with vancomycin (P=0.0029). The cost of laboratory tests for linezolid was 172.30 (SD=128.90) per stay vs. 330.70 (SD=198.40) for vancomycin (P=0.0005). The acquisition cost of linezolid per stay was not different from vancomycin based on the price of the generic drug (54.92 [SD=20.54] vs. 40.30 [SD=22.70]). After weighting by the duration of stay observed, the mean cost per hospital stay was 47,411.50 for linezolid and 57,694.0 for vancomycin (NSD). CONCLUSION: These results, in favor of linezolid, support other former pharmacoeconomic study based on models. The mean cost per hospitalization stay was not statistically different between the two study groups, but a trend in favor of linezolid is emerging.
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Infección Hospitalaria/tratamiento farmacológico , Linezolid/economía , Neumonía Estafilocócica/tratamiento farmacológico , Vancomicina/economía , Anciano , Costos y Análisis de Costo , Infección Hospitalaria/economía , Infección Hospitalaria/enfermería , Grupos Diagnósticos Relacionados , Costos de los Medicamentos , Economía de la Enfermería , Femenino , Francia , Hospitalización/economía , Hospitales Urbanos/economía , Humanos , Infusiones Intravenosas/economía , Tiempo de Internación/economía , Linezolid/administración & dosificación , Linezolid/uso terapéutico , Masculino , Persona de Mediana Edad , Neumonía Estafilocócica/economía , Neumonía Estafilocócica/enfermería , Estudios Retrospectivos , Staphylococcus aureus/efectos de los fármacos , Vancomicina/administración & dosificación , Vancomicina/uso terapéuticoRESUMEN
We present a prospective, observational study evaluating the incidence of medication errors (ME) in a university hospital pediatric emergency department and describe their characteristics and determinants. A systematic analysis of the handwritten prescriptions was conducted by a clinician and pharmacist. Of 11,573 consecutively studied prescriptions in children under 15 years of age, the ME incidence was 0.9% (n=102). The incidence of errors found was statistically significantly higher in children older than 5 years (OR=2.05; P=0.026). There was no significant difference regarding the time of admission (P=0.544), the day of the week (P=0.940), or the affluence of people in attendance at the emergency department. The errors observed were all prescription errors. Most errors were related to analgesic (51%) and antibiotic (30%) treatments. No serious errors were reported. CONCLUSION: We found a low incidence of medication errors in this study. The validation of prescriptions by a senior multidisciplinary staff could contribute to limited medication errors. Measures should be continued to further reduce the incidence of drug errors by calling the attention of prescribers to the most common situations at risk of ME.
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Prescripciones de Medicamentos/estadística & datos numéricos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Errores de Medicación/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Hospitales Universitarios/estadística & datos numéricos , Humanos , Incidencia , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.
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Biomarcadores de Tumor/metabolismo , Canales de Calcio Tipo T/metabolismo , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutáneas/diagnóstico , Proliferación Celular/fisiología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Melanoma/mortalidad , Recurrencia Local de Neoplasia/etiología , Nevo Pigmentado/mortalidad , Pronóstico , Neoplasias Cutáneas/mortalidad , Regulación hacia ArribaRESUMEN
Rational use of antibiotic has become a national and international health priority to fight against the emergence of multiresistant bacteria. Neonates are particularly exposed to antibiotic treatments because of their high susceptibility to severe infection and the lack of specificity of sepsis signs that make diagnosis difficult. This population is also particularly susceptible to microbiota disruption due to antibiotic treatment. Implementation of antibiotic stewardship in neonate is then an urgent need. According to a literature review, principles of antibiotic stewardship implementation in neonate are based on: (i) a multidisciplinary team comprising infectious disease specialists and aware of neonatal specificities (diagnosis, bacterial epidemiology, pharmacology) ; (ii) clear and easy-to-evaluate goals discussed a priori with neonatologists ; (iii) short-term assessment of the impact on antibiotic consumption and antimicrobial resistance ; (iv) enablement of the healthcare professionals within the ward to enhance the sustainability and (v) support from the institution.
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OBJECTIVES: To describe the outcome and risk factors for treatment failure of 76 Gram-negative bacilli (GNB) prosthetic joint infections (PJIs) managed with a curative intent according to a standardized protocol derived from published guidelines. METHODS: We analysed data from all the cases of GNB-PJI treated surgically over an 8 year period. Treatment failure was defined as persistence or recurrence of PJI signs during follow-up, resulting in additional surgery and/or antibiotic administration or death. RESULTS: Treatment failure within the follow-up period (medianâ=â2.6 years) was observed in 16 of 76 (21.1%) patients. The failure rate was similar whether the patients were treated with fluoroquinolones in the whole cohort (22.4% versus 16.7%, Pâ=â0.75) and after stratification according to the surgical procedure. The low failure rate observed in patients not receiving fluoroquinolones might be explained by the standardized attitude of maintaining intravenous ß-lactams throughout treatment duration (medianâ=â90 days). In multivariate analysis, C-reactive protein level ≥175 mg/L was significantly associated with treatment failure (adjusted HRâ=â7.75, 95% CIâ=â2.66-22.59, Pâ<â0.0001). CONCLUSIONS: Management according to standardized procedures may improve the prognosis of GNB-PJI. Intravenous ß-lactams, continued for 3 months, should be considered an effective alternative to fluoroquinolones.
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Antibacterianos/uso terapéutico , Fluoroquinolonas/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del TratamientoRESUMEN
Fluoroquinolones are recommended for the treatment of bone and joint infections (BJIs), and levofloxacin is commonly used in this setting. However, no pre-marketing clinical study has supported its use, especially its dosage, for treating BJIs. This study aimed to assess the benefit-risk ratio of levofloxacin administered orally at a standard dosage of 500 mg once daily (OD) in a cohort of patients with BJIs. The medical records of patients admitted to a large French teaching hospital for BJI over a 1-year period and managed by a multidisciplinary team were reviewed. Patient data were recorded on a standardised form and the outcome was assessed at the end of antibiotic treatment and after 1-year of follow-up. A total of 230 patients were included, of whom 79 were treated with an antibiotic regimen including levofloxacin (34%). Most BJIs (97%) were surgically treated by wound debridement and/or removal or replacement of the infected device. Adverse drug reactions to levofloxacin leading to treatment discontinuation occurred in three patients (4%). The antibiotic treatment duration was significantly longer in patients treated with levofloxacin compared with other antibiotic regimens (median, 13 weeks vs. 6 weeks). Post-treatment outcomes were considered favourable (total or partial recovery, including orthopaedics aftermath) in 89-93% of patients, with no significant difference between treatment groups. In conclusion, oral levofloxacin at 500 mg OD is a well-tolerated and efficacious antibiotic treatment for BJIs. Our approach of following-up all treated patients is a useful way to validate specific clinical practices.