Dual excitation spectral autofluorescence lifetime and reflectance imaging for fast macroscopic characterization of tissues.

Advancements in optical imaging techniques have revolutionized the field of biomedical research, allowing for the comprehensive characterization of tissues and their underlying biological processes. Yet, there is still a lack of tools to provide quantitative and objective characterization of tissues that can aid clinical assessment in vivo to enhance diagnostic and therapeutic interventions. Here, we present a clinically viable fiber-based imaging system combining time-resolved spectrofluorimetry and reflectance spectroscopy to achieve fast multiparametric macroscopic characterization of tissues. An essential feature of the setup is its ability to perform dual wavelength excitation in combination with recording time-resolved fluorescence data in several spectral intervals. Initial validation of this bimodal system was carried out in freshly resected human colorectal cancer specimens, where we demonstrated the ability of the system to differentiate normal from malignant tissues based on their autofluorescence and reflectance properties. To further highlight the complementarity of autofluorescence and reflectance measurements and demonstrate viability in a clinically relevant scenario, we also collected in vivo data from the skin of a volunteer. Altogether, integration of these modalities in a single platform can offer multidimensional characterization of tissues, thus facilitating a deeper understanding of biological processes and potentially advancing diagnostic and therapeutic approaches in various medical applications.

Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos / Lynch syndrome: impact of the characterization of families based on genetic studies

El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes) MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p <0.01), que las 27 sin mutaciones. La implementación de estudios genéticos permitió caracterizar variables demográficas en base a la identificación de mutaciones germinales asociadas al síndrome de Lynch, identificándose dos grupos diferenciados por la edad de afectación y la incidencia de tumores extracolónicos (AU)

The aim of this study was to characterize demographically and molecularly families diagnosed with Lynch syndrome based on genetic studies. Families with a genetic study performed between 1996 and 2017 (sequencing and/or determination of large rearrangements of a mismatch repair gene at least) were selected from the prospective database REM-CCR of Hospital Italiano de Buenos Aires (Clinical trials. Gov NCT02781337). Fifty families fulfilled Amsterdam criteria were analyzed. Pathogenic variants were found in 23 out of 50 (46%) families, being 21 pathogenic and 2 likely pathogenic. The 28.6% of the pathogenic variants were originally described in this series. Among them, the variant c.1911del in MSH2 in a family with breast cancer aggregation and a founder MLH1 mutation from Piedmont, Italy (c.2252_2253del) were identified. Affected genes include MSH2 (13 variants), MLH1 (9 variants), PMS2 (1 variant). Mutations detection rates was 46%. Those families with an identified mutation (n=23) had a lower median age of cancer onset (46 vs. 50 years, p=0.02) and a higher incidence of extra-colorectal tumors (90.5% vs. 45.8%, p<0.01) than those without identified mutations (n=27). The implementation of genetic studies allowed characterizing demographic variables based on the identification of germline mutations associated with Lynch syndrome. Two groups, Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos 3 differentiated by the age of cancer onset and the incidence of extracolonic tumors were characterized (AU)