Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis.
We ...aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19). Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19).
5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women. The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%). In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2<92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered.
In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.
ObjectiveToxic thyroid adenoma (TA) is a common cause of hyperthyroidism. Mutations in the TSH receptor (TSHR) gene, and less frequently in the adenylate cyclase-stimulating G alpha protein (GNAS) ...gene, are well established causes of TA in Europe. However, genetic causes of TA remain unknown in a small percentage of cases. We report the first study to investigate mutations in TSHR, GNAS, protein kinase, cAMP-dependent, regulatory, type I alpha (PRKAR1A) and RAS genes, in a large series of TA from Galicia, an iodine-deficient region in NW Spain.Design and methodsEighty-five TA samples were obtained surgically from 77 hyperthyroid patients, operated on for treatment of non-autoimmune toxic nodular goitre. After DNA extraction, all coding exons of TSHR, GNAS and PRKAR1A genes, and exons 2 and 3 of HRAS, KRAS and NRAS were amplified by PCR and sequenced. Previously unreported mutants were cloned in expression vectors and their basal constitutive activities were determined by quantification of cAMP response element (CRE)-luciferase activity in CO7 cells transfected with wild-type and mutant plasmids.ResultsTSHR gene mutations were found in 52 (61.2%) samples, GNAS gene mutations in 4 (4.71%) samples and no PRKAR1A or RAS mutations were found. Only three previously unreported mutations were found, two affecting the TSHR, A623F and I635V, and one affecting the G-protein α-subunit (Gsα), L203P. All mutant proteins showed higher CRE-luciferase activity than their wild-type counterparts.ConclusionsTA in a hyperthyroid population living in Galicia, a Spanish iodine-deficient region, harbours elevated frequencies of TSHR and GNAS mutations activating the cAMP pathway. However, the genetic cause of TA was undetermined in 34% of the TA samples.
Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis.
We ...aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19).
Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19).
5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65–82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women.
The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%).
In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85–6.58), heart disease (2.32, 1.47–3.66), liver disease (4.69, 1.94–11.62), partial dependence (2.41, 1.34–4.33), total dependence (7.21, 2.60–21.82), fatigue (1.84, 1.16–2.93), arthromialgias (0.45, 0.26–0.78), SatO2<92% (4.58, 2.97–7.17), elevated LDH (2.61, 1.51–4.69) and abnormal decreased Blood Pressure (3.57, 1.81–7.15). Analitical parameters are also significant altered.
In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.
Trabajos previos parecen coincidir en la mayor mortalidad de los pacientes con cáncer y COVID-19. La identificación de posibles factores pronósticos en el momento del ingreso podría ayudar a identificar a los pacientes con mal pronóstico.
Nos propusimos explorar las características y la evolución de los pacientes con cáncer y COVID-19 ingresados en un registro internacional multicéntrico (HOPE COVID-19).
Nuestro objetivo principal es definir aquellas características que nos permitan identificar a los pacientes con cáncer de peor pronóstico (mortalidad en los 30 días siguientes al diagnóstico de COVID-19).
En este registro se ha recogido a 5.838 pacientes, de los cuales 770 tenían cáncer entre sus antecedentes. La mortalidad hospitalaria alcanzó a 258 pacientes (33,51%). La mediana fue de 75 años (65-82). En cuanto a la distribución por sexo, el 34,55% de los pacientes eran mujeres (266/770).
La distribución por tipo de cáncer: genitourinario 238/745 (31,95%), digestivo 124/745 (16,54%) y hematológico 95/745 (12,75%).
En el análisis de regresión multivariante, los factores que se asocian de forma independiente con la mortalidad al ingreso son: insuficiencia renal (OR 3,45; IC 97,5%: 1,85-6,58), cardiopatía (2,32; 1,47-3,66), hepatopatía (4,69; 1,94-11,62), dependencia parcial (2,41; 1,34-4,33), dependencia total (7,21; 2,60-21,82), fatiga (1,84, 1;16-2,93), artromialgias (0,45; 0,26-0,78), SatO2 <92% (4,58; 2,97-7,17), LDH elevada (2,61; 1,51-4,69) y disminución anormal de la presión arterial (3,57; 1,81-7,15). Los parámetros analíticos también están significativamente alterados.
En los pacientes con cáncer del registro HOPE, la mortalidad a los 30 días por cualquier causa es elevada y se asocia a factores clínicos fácilmente identificables a su llegada al hospital. La identificación de estos pacientes puede ayudar a iniciar tratamientos más intensivos desde el principio y evaluar el pronóstico de estos pacientes.
Abstract
Aim: To analyze correlation between tumor subtypes obtained by expression profiling and by miR profiling in colon cancer and to identify miR targets in the colon tumors. Novel tumor subtypes ...have been identified in colon cancer with different clinical behavior. A gene signature associated with high-stroma recognized poor outcome patients (1). A similar classification associated high-stroma-subtype to an EMT-subtype and to a diferent response to cemotherapy treatment (2,3).
Methods: mRNA and miR expression profiling were analyzed in 88 colorectal tumors (24 Dukes A, 26 B, 19 C, 19 D) using gene expression and miR microarrays. Hierarchical clustering was used to uncover tumor subtypes TALASSO software (http://talasso.cnb.csic.es) was used to find miR targets and their correlation wth mRNA expression. Pathways analysis was carried out using GeneCodis software (http://genecodis.cnb.csic.es).
Results: There was a clear association of the tumor subtyes obtained by expression profiling wih the tumor subtypes obtained by miR profiling (p < 0.001). Stroma (p < 0.001) and BRAF mutations (p = 0.024) were also associated to the miR pofiling classificaton. 788 genes showed a significant (p < 0.05) interaction with specific miRs. Pathways jointly regulated by mRNAs and miRs showed differences between tumor subtypes. Relevant KEGG and Panther pathways identified were related to ECM-receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, integrin sigaling and inflammation mediated by chemokine and cytokine signaling pahways as well as WNT and TGFbeta signaling pathways.
Conclusions: 1. There is a clear correlation of tumor classification obtained by expression profiling and by miR profiling 2. Stromal genes and BRAF mutations are asociated to both classifications 3. Pathways related to extracellular matrix and inflamation are implicated References 1-Perez-Villamil et al. BMC Cancer 2012 12:260 2- Schlicker A et al. BMC Medical Genomics 2012 5:66 3- Roepman P et al.Int J Cancer 2013 134:552.
Disclosure: All authors have declared no conflicts of interest.
The incidence of cystic fibrosis (CF) and the frequency of the variants reported for CFTR depend on the population; furthermore, CF symptomatology is characterized by obstructive lung disease and ...pancreatic insufficiency among other symptoms, which are reliant on the individual's genotype. The Ecuadorian population is a mixture of Native Americans, Europeans, and Africans. That population admixture could be the reason for the new mutations reported in a previous study by Ruiz et al. (2019). A panel of 46 Ancestry Informative Markers was used to estimate the ancestral proportions of each available sample (12 samples in total). As a result, the Native American ancestry proportion was the most prevalent in almost all individuals, except for three patients from Guayaquil with the mutation c.757G>A:p.Gly253Arg; c.1352G>T:p.Gly451Val who had the highest European composition.
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