Identification of novel biomarkers in the early diagnosis of malignant melanoma by untargeted liquid chromatography coupled to high-resolution mass spectrometry-based metabolomics: a pilot study.

BACKGROUND: Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. OBJECTIVES: To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. METHODS: In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. RESULTS: We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. CONCLUSIONS: These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.

Melanoma is a type of skin cancer that can be deadly if it is not detected at an early stage. Unfortunately, the early detection of melanoma is challenging. Our team has developed a model that could be used to predict whether a person has stage I malignant melanoma based on blood serum analysis. The model was trained on data from a group of people with melanoma and it was found to be accurate in predicting melanoma at an early stage. This means that the model could be used to identify people who have skin cancer before it progresses and becomes more complicated to treat. Although the researchers recommend that further studies are conducted to validate the model in a larger population of people, this research could help with the early diagnosis of melanoma and work toward improving survival rates.

Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer.

PURPOSE: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. EXPERIMENTAL DESIGN: We analyzed tumor samples from 58 patients with ES-SCLC enrolled in two multicenter single-arm phase IIIb studies evaluating frontline chemoimmunotherapy in Spain: n = 32 from the IMfirst trial and n = 26 from the CANTABRICO trial. We used the GeoMx Digital Spatial Profiler system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). RESULTS: Subtype distribution was found to be similar between bothcohorts, except for SCLC-P, which was not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple coexisting transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity was not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ≥12 months) contained an IFNγ-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. CONCLUSIONS: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Preexisting IFNγ-driven immunity and mitochondrial metabolism seem to be correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.

Contacto piel a piel inmediato: efecto sobre el estado de ansiedad y depresión materna posparto y sobre la adaptabilidad neonatal hacia la lactancia materna precoz / Early skin to skin contac: effect on mother`s anxiety and depression levels after delivery and on early neonatal adaptation to early breastfeeding

Objetivo: Demostrar el efecto del contacto piel a piel inmediato sobre los niveles de ansiedad y depresión materna a las 2 y 48 horas posparto; así como sobre la adaptación neonatal hacia la lactancia materna inmediata y sobre los niveles de satisfacción materna sobre el parto en sí. Material y métodos: Se realizó un estudio prospectivo, randomizado, a doble ciego (ensayo clínico) comparando dos grupos formados de manera aleatoria: grupo de estudio (CPPI) n=38 y grupo de control n =41. El grupo de estudio fue beneficiado con el contacto piel a piel inmediato de 30 minutos de duración. Se aplicaron las siguientes escalas a las 2 y 48 horas posparto: Escala hospitalaria para la ansiedad y depresión (HAD) y escala de Hamilton para la ansiedad. A las dos horas de vida los recién nacidos fueron puestos sobre el pecho materno, observándose cuántos de ellos lograron éxito en la lactancia materna inmediata. Se interrogó a las madres sobre la percepción y satisfacción hacia la experiencia del parto en si. Resultados: Los niveles de ansiedad y depresión materna fueron menores en el grupo de estudio (CPPI) a las 48 horas posparto comparado con los del grupo de control (p menor 0,0001), tanto en sus puntajes absolutos como el valorarlos según los grados del trastorno estudiado; mientras que a las 2 horas posparto no se halló diferencia significativa. Los recién nacidos del grupo de estudio lograron mayor éxito en la lactancia materna inmediata versus los del grupo de control (29 de 38 versus 12 de 41, p menor 0,0001). El grado de satisfacción sobre la percepción materna del parto fue mayor en el grupo de estudio (p menor que 0,0001).

Granuloma inguinal (Donovanosis) de la encía y regiones submandibulares / Granuloma inguinale (Donovanosis) of the gingiva and submandibular regions

El granuloma inguinal (Donovanosis) de la cavidad oral es muy raro, sin embargo representa la manifestación extragenital mas frecuente de esta infección producida por la bacteria gram negativa Calymmatobacterium granulomatis. Se describe un caso de donovanosis gingival en un hombre homosexual de 19 años de edad. Las lesiones gingivales se presentaron como úlceras microgranulomatosas combinadas con zonas esponjosas. El paciente también tenía lesiones en las regiones submandibulares y perianal. El diagnóstico se estableció por biopsia gingival. En este tejido, las secciones teñidas con hematoxilina - eosina mostraron una marcada reacción granulomatosa compuesta por histiocitos, mezclados con abundante cantidad de neutrófilos y pocas células plasmática. Los cuerpos de Donovan fueron identificados usando la coloración de Warthin-Starry. Se discute el diagnóstico clínico diferencial así como el cuadro histopatológico. Considerando el comportamiento sexual del paciente se sugiere que el compromiso gingival y submaxilar probablemente representaban múltiples sitios primarios de infección por C.granulomatis. Sin embargo, la autoinoculación no puede ser descartada. Donovanosis debe ser considerado en el diagnóstico diferencial de lesiones granulomatosas que afectan la mucosa oral, particularmente cuando se presentan en pacientes promiscuos.