Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

7th Drug hypersensitivity meeting: part two

No abstract availabl

Solid pseudopapillary tumors of the pancreas: diagnosis and curative treatment

Objetivos: dar a conocer a través de una serie de casos clínicos una entidad poco frecuente, con una presentación clínica y unos hallazgos radiológicos concretos, que permiten establecer un diagnóstico y un tratamiento que será en la mayoría de los casos curativo. Pacientes y métodos: se realizó un estudio descriptivo y retrospectivo de los casos diagnosticados y tratados quirúrgicamente en una Unidad Pancreático-Biliar de un hospital universitario, durante el periodo comprendo entre marzo de 1999 y septiembre de 2005. Resultados: la incidencia fue de 6 pacientes mujeres, con una edad media de 33,5 años (rango 11-72). La clínica más común fue la de dolor y masa abdominal palpable. La tomografía computerizada fue diagnóstica en tres de las pacientes, en las tres restantes se estableció el diagnóstico diferencial con el tumor neuroendocrino. El tratamiento quirúrgico fue individualizado a cada paciente según los hallazgos y las imágenes visualizadas en la tomografía computerizada. El estudio anatomopatológico confirmó el diagnóstico de presunción, informándose de un caso de carcinoma sólido-pseudopapilar de páncreas. La estancia hospitalaria fue de 18,16 días (rango 8-30). Mortalidad de 0%. En el seguimiento con una media de 46,3 meses (rango 12-76), no existen recidivas. Conclusiones: la presencia en una mujer joven de una lesión voluminosa en el páncreas, debe hacernos pensar en el tumor sólido pseudopapilar. Debido a su bajo potencial de malignidad y a la existencia de unos patrones radiológicos concretos, su diagnóstico debe ser preciso, ya que el tratamiento quirúrgico radical es curativo

A Cohort of Patients with COVID-19 in a Major Teaching Hospital in Europe

BACKGROUND: Since the confirmation of the first patient infected with SARS-CoV-2 in Spain in January 2020, the epidemic has grown rapidly, with the greatest impact on the region of Madrid. This article describes the first 2226 adult patients with COVID-19, consecutively admitted to La Paz University Hospital in Madrid. METHODS: Our cohort included all patients consecutively hospitalized who had a final outcome (death or discharge) in a 1286-bed hospital of Madrid (Spain) from 25 February (first case admitted) to 19 April 2020. The data were manually entered into an electronic case report form, which was monitored prior to the analysis. RESULTS: We consecutively included 2226 adult patients admitted to the hospital who either died (460) or were discharged (1766). The patients’ median age was 61 years, and 51.8% were women. The most common comorbidity was arterial hypertension (41.3%), and the most common symptom on admission was fever (71.2%). The median time from disease onset to hospital admission was 6 days. The overall mortality was 20.7% and was higher in men (26.6% vs. 15.1%). Seventy-five patients with a final outcome were transferred to the intensive care unit (ICU) (3.4%). Most patients admitted to the ICU were men, and the median age was 64 years. Baseline laboratory values on admission were consistent with an impaired immune-inflammatory profile. CONCLUSIONS: We provide a description of the first large cohort of hospitalized patients with COVID-19 in Europe. Advanced age, male sex, the presence of comorbidities and abnormal laboratory values were more common among the patients with fatal outcomes

Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis

International audienceSimple Summary The features of preoperative systemic anticancer therapy associated with best outcomes after resection of initially-irresectable liver metastases from colorectal cancer are yet to be identified. We harnessed data from a prospective international surgical database (LiverMetSurvey) to explore the duration and modalities of preoperative systemic anticancer therapy associated with longer overall survival in this clinical setting. Our study included 2793 patients having undergone liver surgery after preoperative systemic anticancer treatment for initially irresectable disease. We found that short (<7 or <13 cycles in 1st or 2nd line, respectively) duration was associated with longer survival outcomes, independently from other prognostic factors. Conversely, all the comparisons between different conventional active regimens displayed similar results. Our findings support the recommended onco-surgical approach of aiming at performing liver surgery as soon as technically feasible after response to preoperative systemic anticancer therapy in hepatic metastases from colorectal cancer, initially not amenable to surgery. The results of this study also suggest that, provided the systemic anticancer therapy regimen is active, the choice of the drugs used bears overall little if any impact on the outcomes. Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes. Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes