Prevalence and Distribution of MUTYH Pathogenic Variants, Is There a Relation with an Increased Risk of Breast Cancer?

BACKGROUND: MUTYH has been implicated in hereditary colonic polyposis and colorectal carcinoma. However, there are conflicting data refgarding its relationship to hereditary breast cancer. Therefore, we aimed to assess if MUTYH mutations contribute to breast cancer susceptibility. METHODS: We retrospectively reviewed 3598 patients evaluated from June 2018 to June 2023 at the Hereditary Cancer Unit of La Paz University Hospital, focusing on those with detected MUTYH variants. RESULTS: Variants of MUTYH were detected in 56 patients (1.6%, 95%CI: 1.2-2.0). Of the 766 patients with breast cancer, 14 patients were carriers of MUTYH mutations (1.8%, 95%CI: 0.5-3.0). The prevalence of MUTYH mutation was significantly higher in the subpopulation with colonic polyposis (11.3% vs. 1.1%, p < 0.00001, OR = 11.2, 95%CI: 6.2-22.3). However, there was no significant difference in the prevalence within the subpopulation with breast cancer (1.8% vs. 1.5%, p = 0.49, OR = 1.2, 95%CI: 0.7-2.3). CONCLUSION: In our population, we could not establish a relationship between MUTYH and breast cancer. These findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in breast cancer risk.

Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study

Background Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. Methods We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). Results Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. Conclusions In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype (AU)

Efficacy of second and third lines of treatment in advanced soft tissue sarcomas: a real-world study.

BACKGROUND: Soft tissue sarcomas (STSs) are an uncommon and heterogeneous group of tumours. Several drugs and combinations have been used in clinical practice as second-line (2L) and third-line (3L) treatment. The growth modulation index (GMI) has previously been used as an exploratory efficacy endpoint of drug activity and represents an intra-patient comparison. METHODS: We performed a real-world retrospective study including all patients with advanced STS who had received at least 2 different lines of treatment for advanced disease between 2010 and 2020 at a single institution. The objective was to study the efficacy of both 2L and 3L treatments, analysing the time to progression (TTP) and the GMI (defined as the ratio of TTP between 2 consecutive lines of therapy). RESULTS: Eighty-one patients were included. The median TTP after 2L and 3L treatment was 3.16 and 3.06 months, and the median GMI was 0.81 and 0.74, respectively. The regimens most frequently used in both treatments were trabectedin, gemcitabine-dacarbazine, gemcitabine-docetaxel, pazopanib and ifosfamide. The median TTP by each of these regimens was 2.80, 2.23, 2.83, 4.10, and 5.00 months, and the median GMI was 0.78, 0.73, 0.67, 1.08, and 0.94, respectively. In terms of histotype, we highlight the activity (GMI > 1.33) of gemcitabine-dacarbazine in undifferentiated pleomorphic sarcoma (UPS) and in leiomyosarcoma, pazopanib in UPS, and ifosfamide in synovial sarcoma. CONCLUSIONS: In our cohort, regimens commonly used after first-line STS treatment showed only slight differences in efficacy, although we found significant activity of specific regimens by histotype.

MiRNAs in renal cell carcinoma

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer. (AU)

MiRNAs in renal cell carcinoma.

MicroRNAs (miRNAs) are small RNA sequences that act as post-transcriptional regulatory genes to control many cellular processes through pairing bases with a complementary messenger RNA (mRNA). A single miRNA molecule can regulate more than 200 different transcripts and the same mRNA can be regulated by multiple miRNAs. In this review, we highlight the importance of miRNAs and collect the existing evidence on their relationship with kidney cancer.

Safety and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer and hepatitis B or hepatitis C infection.

OBJECTIVES: The safety and efficacy of immunotherapy among patients with history of hepatitis B (HBV) or hepatitis C virus (HCV) infection and non-small cell lung cancer (NSCLC) remains unclear as this population has traditionally been excluded from clinical trials with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: We retrospectively evaluated treatment toxicities and clinical outcomes in nineteen patients with NSCLC and history of past or chronic HBV (16 cases, two of these had HCV co-infection) or chronic HCV infection (five cases), who received a programmed death-1 (PD-1) pathway inhibitor. RESULTS: The overall response rate to immunotherapy was 35 %, and the median progression-free survival was 4.5 months. After ICI initiation, increases in liver function tests (LFTs) from baseline were infrequent and mild, and no patients experienced grade 3 or 4 hepatic immune-related adverse events or required ICI discontinuation or corticosteroid administration for management of hepatic toxicity. There were no significant changes in viral load or cases of HBV reactivation or HCV flare while on ICI therapy. CONCLUSION: In this case series, treatment with immunotherapy in patients with NSCLC and past or chronic viral hepatitis appears to be safe, and responses to ICIs can be durable in this population. Additional studies are needed in larger cohorts of patients to determine the safety of immunotherapy in patients with chronic viral infections.

Mortalidad en el traumatismo potencialmente grave atendido en un servicio de urgencias de tercer nivel. Evaluación de la escala pronóstico de mortalidad GAP / Mortality in patients with potentially severe trauma in a tertiary care hospital emergency department and evaluation of risk prediction with the GAP prognostic scale

Objetivo: Describir la mortalidad de los pacientes atendidos con traumatismos potencialmente graves (TPG) y la correlación de dicha mortalidad con la escala GAP (Glasgow coma scale, Age, and systolic bloob Pressure). Métodos: Estudio observacional retrospectivo con inclusión de todos los pacientes atendidos en urgencias durante 15 meses con TPG. Se registraron variables epidemiológicas, mecanismo lesional, tipo de traslado, necesidad de intubación orotraqueal extrahospitalaria, consumo de tóxicos, índice de comorbilidad de Charlson (ICC), variables incluidas en la escala de GAP, el destino tras la asistencia en urgencias y al final del episodio y la mortalidad. Resultados: Se incluyeron 864 pacientes. La mortalidad fue mayor en pacientes mayores [57,9 (26,6) vs 41,1 (17,4), p < 0,05] y con mayor puntuación en el ICC [3,3 (2,9) vs 0,9 (1,7)]. La precipitación fue el tipo de accidente con mayor mortalidad (p < 0,001). No hubo asociación entre tóxicos y mortalidad. En los fallecidos tuvieron menor puntuación enla escala del coma de Glasgow [9,1 (5,3) vs 14,8 (1,2), p < 0,001], como la presión arterial sistólica [113,8 (19,8) vs 131,3 (20,7) mmHg, p = 0,012] y la diastólica [60,1 (16,8) vs 77,7 (11,7) mmHg, p = 0,002]. La puntuación en la escala GAP fue menor en los fallecidos frente a los supervivientes [5,1 (4,8) vs 22,6 (1,7), p < 0,001]. En el análisis multivariantese mantuvieron significativos el ICC (OR: 0,704; IC 95%: 0,52-0,96) y la escala GAP (OR: 1,8; IC 95%: 1,45-2,20). Conclusiones: La mortalidad de nuestra serie de pacientes es baja en relación a lo publicado con anterioridad. El GAP es útil como escala pronóstica de mortalidad en nuestra cohorte de pacientes (AU)

Objective: To assess mortality in patients with potentially severe injuries and explore the correlation between mortality and the score on the GAP scale (Glasgow Coma Scale, age, and systolic blood pressure). Methods: Retrospective observational study of all patients with potentially severe injuries treated in an emergency department (ED) over a period of 15 months. We recorded epidemiologic variables, cause of injury, type of transport, need for prehospital orotracheal intubation, substance abuse, Charlson Comorbidity Index (CCI), variables for the GAP prognostic score, destination on discharge from the ED and at the end of the episode, and mortality. Results: Data for 864 patients entered the final analysis. Mortality was higher in older patients (mean [SD] age, 57.9 [26.6] vs 41.1 [17.4], P< 05) and those with a higher mean CCI (3.3 [2.9] vs 0.9 [1.7]). Accident type was a precipitating factor associated with mortality (P< 001), but substance abuse was unrelated. Patients who died had lower mean Glasgow scores (9.1 [5.3] vs 14.8 [1.2], P< 001) and lower mean systolic and diastolic pressures (respectively, 113.8 [19.8] vs 131.3 [20.7] mm Hg, P=.012, and 60.1 [16.8] vs 77.7 [11.7] mm Hg, P=.002). Patients who died also had lower mean GAP scores than survivors (15.1 [4.8] vs 22.6 [1.7], P< 001). Risk factors that remained significant in the multivariate analysis were CCI (odds ratio [OR], 0.704; 95% CI, 0.52-0.96) and GAP score (OR, 1.8; 95% CI, 1.45-2.20). Conclusions: Mortality in our patient series was lower than rates in previously published reports. The GAP score was a useful tool for predicting mortality in the series we studied (AU)

[Mortality in patients with potentially severe trauma in a tertiary care hospital emergency department and evaluation of risk prediction with the GAP prognostic scale]. / Mortalidad en el traumatismo potencialmente grave atendido en un servicio de urgencias de tercer nivel. Evaluación de la escala pronóstico de mortalidad GAP.

OBJECTIVES: To assess mortality in patients with potentially severe injuries and explore the correlation between mortality and the score on the GAP scale (Glasgow Coma Scale, age, and systolic blood pressure). MATERIAL AND METHODS: Retrospective observational study of all patients with potentially severe injuries treated in an emergency department (ED) over a period of 15 months. We recorded epidemiologic variables, cause of injury, type of transport, need for prehospital orotracheal intubation, substance abuse, Charlson Comorbidity Index (CCI), variables for the GAP prognostic score, destination on discharge from the ED and at the end of the episode, and mortality. RESULTS: Data for 864 patients entered the final analysis. Mortality was higher in older patients (mean [SD] age, 57.9 [26.6] vs 41.1 [17.4], P<.05) and those with a higher mean CCI (3.3 [2.9] vs 0.9 [1.7]). Accident type was a precipitating factor associated with mortality (P<.001), but substance abuse was unrelated. Patients who died had lower mean Glasgow scores (9.1 [5.3] vs 14.8 [1.2], P<.001) and lower mean systolic and diastolic pressures (respectively, 113.8 [19.8] vs 131.3 [20.7] mm Hg, P=.012, and 60.1 [16.8] vs 77.7 [11.7] mm Hg, P=.002). Patients who died also had lower mean GAP scores than survivors (15.1 [4.8] vs 22.6 [1.7], P<.001). Risk factors that remained significant in the multivariate analysis were CCI (odds ratio [OR], 0.704; 95% CI, 0.52-0.96) and GAP score (OR, 1.8; 95% CI, 1.45-2.20). CONCLUSION: Mortality in our patient series was lower than rates in previously published reports. The GAP score was a useful tool for predicting mortality in the series we studied.

OBJETIVO: Describir la mortalidad de los pacientes atendidos con traumatismos potencialmente graves (TPG) y la correlación de dicha mortalidad con la escala GAP (Glasgow coma scale, Age, and systolic bloob Pressure). METODO: Estudio observacional retrospectivo con inclusión de todos los pacientes atendidos en urgencias durante 15 meses con TPG. Se registraron variables epidemiológicas, mecanismo lesional, tipo de traslado, necesidad de intubación orotraqueal extrahospitalaria, consumo de tóxicos, índice de comorbilidad de Charlson (ICC), variables incluidas en la escala de GAP, el destino tras la asistencia en urgencias y al final del episodio y la mortalidad. RESULTADOS: Se incluyeron 864 pacientes. La mortalidad fue mayor en pacientes mayores [57,9 (26,6) vs 41,1 (17,4), p < 0,05] y con mayor puntuación en el ICC [3,3 (2,9) vs 0,9 (1,7)]. La precipitación fue el tipo de accidente con mayor mortalidad (p < 0,001). No hubo asociación entre tóxicos y mortalidad. En los fallecidos tuvieron menor puntuación en la escala del coma de Glasgow [9,1 (5,3) vs 14,8 (1,2), p < 0,001], como la presión arterial sistólica [113,8 (19,8) vs 131,3 (20,7) mmHg, p = 0,012] y la diastólica [60,1 (16,8) vs 77,7 (11,7) mmHg, p = 0,002]. La puntuación en la escala GAP fue menor en los fallecidos frente a los supervivientes [5,1 (4,8) vs 22,6 (1,7), p < 0,001]. En el análisis multivariable se mantuvieron significativos el ICC (OR: 0,704; IC 95%: 0,52-0,96) y la escala GAP (OR: 1,8; IC 95%: 1,45-2,20). CONCLUSIONES: La mortalidad de nuestra serie de pacientes es baja en relación a lo publicado con anterioridad. El GAP es útil como escala pronóstica de mortalidad en nuestra cohorte de pacientes.