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5.
J Mol Diagn ; 22(8): 968-974, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32565306

RESUMEN

Clinical molecular laboratory professionals are at the frontline of the response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, providing accurate, high-quality laboratory results to aid in diagnosis, treatment, and epidemiology. In this role, we have encountered numerous regulatory, reimbursement, supply-chain, logistical, and systems challenges that we have struggled to overcome to fulfill our calling to provide patient care. In this Perspective from the Association for Molecular Pathology Infectious Disease Subdivision Leadership team, we review how our members have risen to these challenges, provide recommendations for managing the current pandemic, and outline the steps we can take as a community to better prepare for future pandemics.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Pandemias , Patología Molecular , Neumonía Viral/epidemiología , Infecciones por Coronavirus/diagnóstico , Humanos , Liderazgo , Técnicas de Diagnóstico Molecular , Patología Molecular/organización & administración , Neumonía Viral/diagnóstico , Sociedades Médicas , Estados Unidos/epidemiología
6.
Int Endod J ; 53(9): 1181-1191, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32496605

RESUMEN

AIM: To explore a set of inflammatory biomarkers obtained from dentinal fluid (DF) from patients with symptomatic irreversible pulpitis (IP), reversible pulpitis (RP) and normal pulp (NP). METHODOLOGY: A cross-sectional exploratory study was performed, recruiting 64 patients on the basis of their respective pulp condition. DF samples were obtained from all patients (23, from IP patients; 20, from RP patients; and 21, from NP patients). Quantification of biomarkers was performed using a Luminex® MAGPIX platform system and multiplex assay kits. The Kruskal-Wallis test was used for comparisons with regard to pulp state. A simple logistic regression model and the odds ratio (OR) with a 95% level of confidence (P = 0.05) were used to evaluate associations between biomarker levels and pulpal diagnosis. The performance discrimination of the biomarkers was evaluated through the construction of a receiver operating characteristic (ROC) curve by calculating the area under the curve (AUC) for IP versus RP after logistic regression modelling. Youden criteria were used to establish cut-off points for biomarkers alone with AUC > 70 and P-value < 0.05, or estimated probabilities from the multivariable logistic model. RESULTS: The biomarkers that had significantly higher values in participants with IP versus RP were IL-1α, VEGF-α and FGF acid (P < 0.05). FGF acid (OR: 12.62; P = 0.0085; CI 95% 1.91-83.29) and VEGF-α (OR: 2.61; P = 0.0252; CI 95% 1.13-6.03) were associated with pulp diagnoses of IP versus RP. The AUC-ROC curve for FGF acid was 0.79. The model containing FGF acid, IL-1α, IL-6 and TIMP-1 had an AUC-ROC of 0.92 for IP versus RP with a significant difference from the FGF acid ROC curve (P = 0.0231). CONCLUSIONS: Dentinal fluid could be used to assay pulpal mediators in the molecular diagnosis of pulpitis. Despite the limitation of the clinical diagnostics used in the present study, it was possible to detect a difference between irreversible symptomatic pulpitis and reversible pulpitis associated with the following combined biomarkers: FGF acid + IL-6 + IL-1α, +TIMP-1.


Asunto(s)
Pulpitis , Biomarcadores , Estudios Transversales , Pulpa Dental , Líquido de la Dentina , Humanos , Patología Molecular
7.
JCI Insight ; 5(12)2020 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-32379723

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of human coronavirus disease 2019 (COVID-19), emerged in Wuhan, China, in December 2019. The virus rapidly spread globally, resulting in a public health crisis including almost 5 million cases and 323,256 deaths as of May 21, 2020. Here, we describe the identification and evaluation of commercially available reagents and assays for the molecular detection of SARS-CoV-2 in infected FFPE cell pellets. We identified a suitable rabbit polyclonal anti-SARS-CoV spike protein antibody and a mouse monoclonal anti-SARS-CoV nucleocapsid protein (NP) antibody for cross-detection of the respective SARS-CoV-2 proteins by IHC and immunofluorescence assay (IFA). Next, we established RNAscope in situ hybridization (ISH) to detect SARS-CoV-2 RNA. Furthermore, we established a multiplex FISH (mFISH) to detect positive-sense SARS-CoV-2 RNA and negative-sense SARS-CoV-2 RNA (a replicative intermediate indicating viral replication). Finally, we developed a dual staining assay using IHC and ISH to detect SARS-CoV-2 antigen and RNA in the same FFPE section. It is hoped that these reagents and assays will accelerate COVID-19 pathogenesis studies in humans and in COVID-19 animal models.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/virología , Neumonía Viral/virología , Animales , Anticuerpos Antivirales/inmunología , Antígenos Virales/aislamiento & purificación , Betacoronavirus/genética , Betacoronavirus/inmunología , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/patología , Formaldehído , Humanos , Inmunohistoquímica , Hibridación in Situ , Ratones , Proteínas de la Nucleocápside/inmunología , Pandemias , Adhesión en Parafina/métodos , Patología Molecular/métodos , Neumonía Viral/patología , ARN Viral/aislamiento & purificación , Conejos , Fijación del Tejido/métodos
8.
Emerg Infect Dis ; 26(8): 1944-1946, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32433015

RESUMEN

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) created an exceptional situation in which numerous laboratories in Europe simultaneously implemented SARS-CoV-2 diagnostics. These laboratories reported in February 2020 that commercial primer and probe batches for SARS-CoV-2 detection were contaminated with synthetic control material, causing delays of regional testing roll-out in various countries.


Asunto(s)
Artefactos , Betacoronavirus/genética , Técnicas de Laboratorio Clínico/normas , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Juego de Reactivos para Diagnóstico/normas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/normas , Betacoronavirus/patogenicidad , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/virología , Cartilla de ADN/análisis , Cartilla de ADN/síntesis química , Sondas de ADN/análisis , Sondas de ADN/síntesis química , Diagnóstico Tardío , Pruebas Diagnósticas de Rutina , Europa (Continente)/epidemiología , Humanos , Laboratorios/organización & administración , Laboratorios/normas , Pandemias , Patología Molecular , Neumonía Viral/virología , ARN Replicasa/genética , Juego de Reactivos para Diagnóstico/provisión & distribución , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/estadística & datos numéricos , Proteínas del Envoltorio Viral/genética
9.
J Clin Pathol ; 73(9): 531-534, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32317291

RESUMEN

Sclerosing pneumocytoma (SP) is a rare benign low-grade tumour of the lung, and typically presents as single discrete coin lesions on imaging. Multiple SP is an exceedingly rare entity and thus reported sparingly. We review the literature on multiple SP, their clinical presentations, histopathology, relevant differential diagnoses and molecular histogenesis of this entity. SP has a predilection for East Asian origin females who have never smoked. Patients are either asymptomatic or have symptoms such as cough, haemoptysis that may be persistent, chest pain if involving the pleura and presents as discrete coin lesion on chest X-ray. Histologically, they are papillary, solid, angiomatoid or sclerotic, or combinations of these four basic patterns. Multiple lesions have the same or slightly different histological patterns. They can be distributed in either lung, in any lobe and can even be bilateral. AKT-1 molecular pathways are pivotal in their molecular pathogenesis. In this review, we further propose a classification based on five types of distribution of multiple SP.


Asunto(s)
Neoplasias Pulmonares/clasificación , Proteínas Proto-Oncogénicas c-akt/genética , Hemangioma Esclerosante Pulmonar/clasificación , Grupo de Ascendencia Continental Asiática , Diagnóstico Diferencial , Femenino , Humanos , Inmunohistoquímica , Pulmón/diagnóstico por imagen , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Patología Molecular , Hemangioma Esclerosante Pulmonar/diagnóstico por imagen , Hemangioma Esclerosante Pulmonar/patología , Hemangioma Esclerosante Pulmonar/terapia , Tomografía Computarizada por Rayos X
10.
Parasit Vectors ; 13(1): 186, 2020 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-32272968

RESUMEN

BACKGROUND: From a veterinary-medical point of view, the stable fly, Stomoxys calcitrans, is perhaps the economically most important blood-sucking muscoid fly species (Diptera: Muscidae), owing to its worldwide occurrence, frequently high local abundance, direct harm caused to livestock, pet animals and humans, as well as its vector role. Considering the latter in the context of protozoan parasites, the stable fly is a mechanical vector of trypanosomes and Besnoitia besnoiti. However, its role as a vector of piroplasms appears to be seldom studied, despite old data suggesting mechanical transmission of babesiae by dipteran flies. METHODS: In this study 395 stable flies (and one Haematobia stimulans) were collected at a cattle farm with known history of bovine theileriosis, and at further nine, randomly chosen locations in Hungary. These flies were separated according to sex (30 of them also cut into two parts: the head with mouthparts and the thorax-abdomen), followed by individual DNA extraction, then screening for piroplasms by PCR and sequencing. RESULTS: In stable flies, Theileria orientalis and T. capreoli were identified at the cattle farm and T. equi was identified in three other locations. At the cattle farm, significantly more male stable flies carried piroplasm DNA than females. There was no significant difference between the ratio of PCR-positive flies between the stable (void of cattle for at least two hours) and the pen on the pasture with cattle at the time of sampling. Among dissected flies (29 S. calcitrans and 1 H. stimulans), exclusively the thoracic-abdominal parts were PCR-positive, whereas the head and mouthparts remained negative. CONCLUSIONS: Theileria DNA is detectable in stable flies, in the case of T. orientalis at least for two hours after blood-feeding, and in the case of T. capreoli also in the absence of infected hosts (i.e. roe deer). Male flies rather than females, and thoracic-abdominal (most likely crop) contents rather than mouthparts may pose a risk of mechanical transmission. These data suggest that it is worth to study further the vector role of stable flies in the epidemiology of theilerioses, in which not the immediate, but rather the delayed type transmission seems possible.


Asunto(s)
Insectos Vectores/parasitología , Muscidae/parasitología , Theileria/aislamiento & purificación , Theileriosis/epidemiología , Animales , Bovinos , Enfermedades de los Bovinos/parasitología , ADN Protozoario , Ciervos/parasitología , Femenino , Hungría , Intestinos/parasitología , Masculino , Patología Molecular/métodos , ARN Ribosómico 18S
11.
Microbiol Res ; 236: 126467, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32248049

RESUMEN

Strains of Xylella fastidiosa subsp. pauca characterized by a specific genotype, the so called sequence type "ST53", have been associated with a severe disease named Olive Quick Decline Syndrome (OQDS). Despite the relevant research efforts devoted to control the disease caused by X. fastidiosa, so far there are no therapeutic means able to cure the infected host plants. As such, the aim of this study was the identification of antagonistic bacteria potentially deployable as bio-control agents against X. fastidiosa. To this end, two approaches were used, i.e. the evaluation of the antagonistic activity of: i) endophytic bacteria isolated from olive trees located in an infected area but showing mild or no symptoms, and ii) Bacillus strains, as they are already known as bio-control agents. Characterization of endophytic bacterial isolates revealed that the majority belonged to different species of the genera Sphingomonas, Methylobacterium, Micrococcus and Curtobacterium. However, when they were tested in vitro against X. fastidiosa ST53 none of them showed antagonistic activity. On the contrary, when strains belonging to different species of the genus Bacillus were included in these tests, remarkable antagonistic activities were recorded. Some B. velezensis strains also produced culture filtrates with inhibitory activity against X. fastidiosa ST53. Taking also into account that two of these B. velezensis strains (namely strains D747 and QST713) are already registered and commercially available as bio-control agents, our results pave the way for further studies aimed at the development of a sustainable bio-control strategy of the OQDS.


Asunto(s)
Antibiosis , Bacillus , Endófitos/aislamiento & purificación , Olea/microbiología , Xylella , Bacillus/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Agentes de Control Biológico/farmacología , ADN Bacteriano/genética , Endófitos/genética , Endófitos/metabolismo , Patología Molecular , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/terapia , Xylella/patogenicidad
12.
Brasília, D.F.; OPAS; 2020-03-21. (OPAS-W/BRA/COVID-19/20-094).
No convencional en Portugués | PAHO-IRIS | ID: phr2-52499

RESUMEN

[Introdução]. A OMS publicou orientações sobre testes laboratoriais para COVID- 19 em casos suspeitos em seres humanos. Devido à propagação global da COVID-19 e ao aumento drástico do número de casos suspeitos e da área geográfica que precisou ser coberta pelos testes laboratoriais, a intensificação da testagem molecular para COVID-19 levou ao desabastecimento global de reagentes para COVID-19 e para outros diagnósticos moleculares. Além dos problemas de abastecimento, há também limitações significativas de capacidade de absorção em muitas regiões, principalmente em países de baixa e média renda. Como parte do Plano Estratégico de Preparação e Resposta, a OMS elaborou recomendações relativas à estratégia de testagem. Essa estratégia baseia-se em três pilares: Todos os países devem aumentar seu nível de preparação, alerta e resposta para identificação, gerenciamento e atendimento de novos casos de COVID-19; os testes laboratoriais são parte integrante dessa estratégia. Os países devem se preparar para responder a diferentes cenários de saúde pública, cientes de que não existe uma abordagem única para gerenciamento de casos e surtos da COVID-19. Cada país deve avaliar o respectivo risco e implementar rapidamente as medidas necessárias, na escala apropriada, para se preparar para possíveis picos de demanda por testes e atendimento clínico e reduzir tanto a transmissão quanto os impactos econômicos, sociais e de saúde pública da COVID-19.


Asunto(s)
Infecciones por Coronavirus , Coronavirus , Infecciones por Coronavirus , Patología Molecular , Diagnóstico
13.
Phytopathology ; 110(7): 1255-1259, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32175826

RESUMEN

The filamentous ascomycete fungus Lachnellula willkommii is the causal agent of European larch canker (ELC), one of the most destructive diseases of larch in Europe and a regulated plant pathogen of quarantine significance in Canada and the United States. L. willkommii was first detected in Massachusetts, North America in 1927 on a larch plantation cultivated with nursery stock imported from Great Britain. Despite the decades of practices aimed at eliminating the pathogen, it has reappeared in coastal areas of Canada and the United States. There is concern ELC could spread throughout the range of eastern larch, a transcontinental species typical of the Boreal forest that spans the North American landscape. There is geographic range overlap between several nonpathogenic indigenous Lachnellula species and the reported distribution of L. willkommii in North America. Morphological and biological methods to distinguish L. willkommii are often inadequate as the fungus does not always produce the phenotypic structures that distinguish it from these other saprophytic Lachnellula species. Whole genome sequencing technologies were used to obtain the draft genome sequences of L. willkommii and six other Lachnellula species. Molecular markers identified from the genomic data may be used to discriminate L. willkommii from its nonpathogenic relatives.


Asunto(s)
Ascomicetos/genética , Larix/genética , Canadá , Europa (Continente) , América del Norte , Patología Molecular , Enfermedades de las Plantas , Reino Unido , Secuenciación Completa del Genoma
14.
Magy Onkol ; 64(1): 25-31, 2020 Mar 17.
Artículo en Húngaro | MEDLINE | ID: mdl-32181759

RESUMEN

The technical developments lead to revolution and speed-up of molecular genetic diagnostics of hereditary cancer syndromes. In those apparently sporadic, solid tumors where the chance of inheritance is higher than 10%, the molecular genetic analysis is indicated. Nowadays these tests are performed using next generation sequencing technologies which allow parallel testing of multiple genes. However, in well-defined cancer syndromes where the clinical presentation clearly suggests the diagnosis and the disease is monogenic, targeted testing is still recommended. Clinical indication of molecular genetic testing and its interpretation is a complex procedure; all steps are regulated. Beside ethical and legal aspects both the laboratory, bioinformatic steps and the interpretation of the results require strong supervision and control. The current review summarizes the genetic alterations responsible for hereditary cancer syndromes and molecular genetic methods which are used during diagnostics in everyday practice.


Asunto(s)
Análisis Mutacional de ADN/métodos , Pruebas Genéticas/métodos , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Patología Molecular/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos
15.
Virchows Arch ; 476(4): 491-497, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32124002

RESUMEN

Molecular pathology is an essential part of pathology complementing conventional morphological tools to obtain a correct integrated diagnosis with appropriate assessment of prognosis and prediction of response to therapy, particularly in cancer. There is a concern about the situation of molecular pathology in some areas of Europe, namely, regarding the central role of pathologists in assessing somatic genomic alterations in cancer. In some countries, there are attempts that other laboratory medicine specialists perform the molecular analysis of somatic alterations in cancer, particularly now when next generation sequencing (NGS) is incorporated into clinical practice. In this scenario, pathologists may play just the role of "tissue providers," and other specialists may take the lead in molecular analysis. Geneticists and laboratory medicine specialists have all background and skills to perform genetic analysis of germline alterations in hereditary disorders, including familial forms of cancers. However, interpretation of somatic alterations of cancer belongs to the specific scientific domain of pathology. Pathologists are necessary to guarantee the quality of the results, for several reasons: (1) The identified molecular alterations should be interpreted in the appropriate morphologic context, since most of them are context-specific; (2) pre-analytical issues must be taken into consideration; (3) it is crucial to check the proportion of tumor cells in the sample subjected to analysis and presence of inflammatory infiltrate and necrosis should be monitored; and 4) the role of pathologists is crucial to select the most appropriate methods and to control the turnaround time in which the molecular results are delivered in the context of an integrated diagnosis. Obviously, there is the possibility of having core facilities for NGS in a hospital to perform the sequence analysis that are open to other specialties (microbiologists, geneticists), but also in this scenario, pathologists should have the lead in assessing somatic alterations of cancer. In this article, we emphasize the importance of interpreting somatic molecular alterations of the tumors in the context of morphology. In this Position Paper of the European Society of Pathology, we strongly support a central role of pathology departments in the process of analysis and interpretation of somatic molecular alterations in cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias/patología , Patólogos , Patología Molecular , Biomarcadores de Tumor/genética , Europa (Continente) , Humanos , Neoplasias/genética , Medicina de Precisión/métodos
16.
Arch Pathol Lab Med ; 144(3): 275-276, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32101057

RESUMEN

This special section includes 4 articles as the proceedings of the Fifth Princeton Integrated Pathology Symposium (PIPS): Genitourinary Pathology, and an update on neuroendocrine tumor of the prostate. The symposium took place at the Princeton Medical Center, Plainsboro, New Jersey, on Sunday April 15, 2018. We hope again that this collection of outstanding reviews will serve as a handy reference for your daily practice.


Asunto(s)
Patología/métodos , Próstata/patología , Neoplasias de la Próstata/patología , Humanos , Masculino , Patología Clínica/métodos , Patología Molecular/métodos , Patología Quirúrgica/métodos , Próstata/metabolismo , Próstata/cirugía , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía
17.
PLoS Comput Biol ; 16(2): e1007503, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32049956

RESUMEN

Molecular diagnosis is an essential step of patient care. An increasing number of Copy Number Variations (CNVs) have been identified that are involved in inherited and somatic diseases. However, there are few existing tools to identify them among amplicon sequencing data generated by Next Generation Sequencing (NGS). We present here a new tool, CovCopCan, that allows the rapid and easy detection of CNVs in inherited diseases, as well as somatic data of patients with cancer, even with a low ratio of cancer cells to healthy cells. This tool could be very useful for molecular geneticists to rapidly identify CNVs in an interactive and user-friendly way.


Asunto(s)
Biología Computacional , Variaciones en el Número de Copia de ADN , Enfermedades Genéticas Congénitas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Neoplasias/genética , Algoritmos , Humanos , Técnicas de Amplificación de Ácido Nucleico/métodos , Patología Molecular/métodos
18.
Parasit Vectors ; 13(1): 52, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-32033615

RESUMEN

BACKGROUND: The Spirorchiidae is a family of blood flukes parasitizing turtles. Spirorchiids may cause a wide range of inflammatory reactions in the vascular system of their host being frequently implicated with stranding and death of sea turtles worldwide. Recent studies revealed the presence of two spirorchiid species in the Mediterranean basin. Our study presents comparative epidemiological data of spirorchiid infections in loggerhead turtles (Caretta caretta) stranded during an eight-year period from Adriatic and Tyrrhenian Seas, and the first report of Neospirorchis Neogen-11 in a green turtle (Chelonia mydas). METHODS: We screened a total of 319 carcasses of loggerhead turtles stranded from January 2011 to December 2018 along the Tyrrhenian coast (n = 111) and the north-western Adriatic coast (n = 208) of Italy using traditional (copromicroscopy and histopathology) and molecular assays. Three green turtles from the Tyrrhenian coast were also included in the study. RESULTS: A total of 56 (17.5%) loggerhead turtles and one green turtle (33.3%) were found to be infected with spirorchiid flukes. Amplification, sequencing of the ITS2 region of the ribosomal RNA gene cluster and BLAST analysis confirmed the presence of Hapalotrema mistroides and Neospirorchis Neogen-11 in 51 (16.0%) and 24 (7.5%) loggerhead turtles, respectively, and Neospirorchis Neogen-11 in an infected green turtle. Differences in prevalence of infection between the two sampling areas were found. CONCLUSIONS: The risk of spirorchiid infection in the Tyrrhenian Sea is lower than in the Adriatic Sea and in general the risk of infection in the Mediterranean is lower than in other geographical locations. Differences in the prevalence of infection between the two sampling areas were related to the differences of regional habitats supporting different abundance of spirorchiid intermediate hosts. A systematic monitoring to evaluate the progress of the infection is recommended, as well as studies on the occurrence and distribution of spirorchiid species from other Mediterranean areas.


Asunto(s)
Trematodos , Infecciones por Trematodos/epidemiología , Tortugas/parasitología , Animales , Genes de Helminto , Mar Mediterráneo/epidemiología , Patología Molecular , Prevalencia , ARN de Helminto/genética , Trematodos/clasificación , Trematodos/aislamiento & purificación
20.
Eur J Cancer ; 127: 41-51, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31982633

RESUMEN

BACKGROUND: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses. METHODS: A specialized physician screened results from molecular analyses for potential biomarkers, irrespective of the diagnostic modality. Best available evidence was retrieved and categorized through establishment of an in-house database and interrogation of publicly available databases. Annotated biomarkers were ranked using predefined evidence levels and subsequently discussed at a molecular tumour board (MTB), which generated treatment recommendations. Subsequent translation into patient treatment and clinical outcomes were followed up. RESULTS: One hundred patients were discussed in the MTB between January 2016 and May 2017. Molecular data were obtained for 70 of 100 patients (50 whole exome/RNA sequencing, 18 panel sequencing, 2 immunohistochemistry (IHC)/microsatellite instability analysis). The MTB generated a median of two treatment recommendations each for 63 patients. Thirty-nine patients were treated: 6 partial responses and 12 stable diseases were achieved as best responses. Genetic counselling for germline events was recommended for seven patients. CONCLUSION: The development of an evidence-based workflow allowed for the clinical interpretation of complex molecular data and facilitated the translation of personalized treatment strategies into routine clinical care. The high number of treatment recommendations in patients with comprehensive genomic data and promising responses in patients treated with combination therapy warrant larger clinical studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Técnicas de Apoyo para la Decisión , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Patología Molecular/estadística & datos numéricos , Medicina de Precisión , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/patología , Pronóstico , Adulto Joven
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