Are Comorbidities Associated With Overall Survival in Patients With Oral Squamous Cell Carcinoma?

Purpose: Oral squamous cell carcinoma (OSCC) is a highly prevalent type of immunogenic cancer with a low survival rate in patients with comorbidities owing to toxic habits. Materials and Methods: A retrospective cohort study was conducted of patients with resectable OSCC at a tertiary Spanish hospital from 2011 to 2014. The primary predictor variables were comorbidity and immune biomarkers. Comorbidity was assessed using the Adult Comorbidity Evaluation–27 (ACE-27) and scored from 1 to 3 (mild to severe decompensation, respectively). The immune biomarkers were neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The primary outcome variable was 5-year overall survival (OS). Other study variables were stage, margin, and neck management. Receiver operating characteristic curves were built for each ratio. For the survey of immune biomarkers, area under the curve was computed to determine cutoff points and investigate their association with OS. Kaplan-Meier estimates of survival and Cox proportional hazards models were used for longitudinal analysis. Results: Overall 215 patients were identified (median age, 67 yr; range, 32 to 96 yr; median follow-up, 31 months; range, 7 to 78 months); 159 patients had at least 1 comorbid condition. Results showed that a severe comorbidity (according to the ACE-27) increased the risk of death by 4 times in patients with OSCC regardless of stage. NLR, dNLR, LMR, and PLR were associated with OS in the univariate study. Cutoff points to predict increased mortality were 3, 1.9, 2.6, and 66 for NLR, dNLR, LMR, and PLR, respectively. Age, comorbidity, stage, margins, and management of the neck were important independent predictors of decreased OS in OSCC. PLR was marginally associated with OS in the multivariate model. Conclusion: These results suggest that comorbidity and NLR, dNLR, LMR, and PLR are associated with 5-year OS in patients with resectable OSCC

Population-based incidence of lymphoid neoplasms : Twenty years of epidemiological data in the Girona province, Spain

Background: The aim of this study was to describe incidence patterns of lymphoid neoplasms in the Girona province (Spain) (1996-2015), and to predict the number of cases in Spain during 2020. Methods: Data were extracted from the Girona cancer registry. Incident cases were classified using the ICD-O-3, third revision, and grouped according to the WHO 2008 classification scheme. Age-adjusted incidence rates to the European standard population (ASRE) were estimated and incidence trends were modeled using Joinpoint. Results: 4367 lymphoid neoplasms were diagnosed in the Girona province. The ASRE for overall lymphoma was 37.1 (95% CI: 36.0; 38.2), with a marked male predominance in almost all subtypes. During 1996-2015, incidence trends remained stable for broader lymphoma categories. According to our predictions, 17,950 new cases of LNs will be diagnosed in Spain in 2020. Conclusions: This 'real-world' data will provide valuable information to better inform etiological hypotheses and plan future health-care services

Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (J(OH)-, mmol/L/min), measured in primary cultured hepatocytes from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 +/- 0.3 vs. 3.1 +/- 0.2, p<0.005). cAMP-stimulated AE2 activity, however, was not different between SHAM and BDL groups (3.7 +/- 0.3 vs. 3.5 +/- 0.3), suggesting that cAMP stimulated insertion into the canalicular membrane of AE2-containing intracellular vesicles, that had remained abnormally internalized after BDL. In conclusion, our results point to the existence of a novel adaptive mechanism in cholestasis aimed to reduce biliary pressure, in which AE2 internalization in hepatocytes might result in decreased canalicular HCO3- output and decreased bile flow.This work was supported by grants from Spanish Carlos III Health Institute (ISCIII) [J. M. Banales (FIS PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129) cofinanced by "Fondo Europeo de Desarrollo Regional" (FEDER); "Instituto de Salud Carlos III" [CIBERehd: J. M. Banales], Spain; BIOEF (Basque Foundation for Innovation and Health Research: EiTB Maratoia BIO15/CA/016/BD to J. M. Banales), Department of Health of the Basque Country (J. M. Banales: 2017111010) and Euskadi RIS3 (J. M. Banales: 2016222001, 2017222014, 2018222029). "Fundacion Cientifica de la Asociacion Espanola Contra el Cancer" (AECC Scientific Foundation, to J. M. Banales). F. A. Crocenzi was recipient of a Young Investigator Scholarship from Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Argentina. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Alternative polyadenylation and salicylic acid modulate root responses to low nitrogen availability

Nitrogen (N) is probably the most important macronutrient and its scarcity limits plant growth, development and fitness. N starvation response has been largely studied by transcriptomic analyses, but little is known about the role of alternative polyadenylation (APA) in such response. In this work, we show that N starvation modifies poly(A) usage in a large number of transcripts, some of them mediated by FIP1, a component of the polyadenylation machinery. Interestingly, the number of mRNAs isoforms with poly(A) tags located in protein-coding regions or 5 '-UTRs significantly increases in response to N starvation. The set of genes affected by APA in response to N deficiency is enriched in N-metabolism, oxidation-reduction processes, response to stresses, and hormone responses, among others. A hormone profile analysis shows that the levels of salicylic acid (SA), a phytohormone that reduces nitrate accumulation and root growth, increase significantly upon N starvation. Meta-analyses of APA-affected and fip1-2-deregulated genes indicate a connection between the nitrogen starvation response and salicylic acid (SA) signaling. Genetic analyses show that SA may be important for preventing the overgrowth of the root system in low N environments. This work provides new insights on how plants interconnect different pathways, such as defense-related hormonal signaling and the regulation of genomic information by APA, to fine-tune the response to low N availability

Linezolid-induced lactic acidosis in two liver transplant patients with the mitochondrial DNA A2706G polymorphism

Mitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism

Conceptual Graphs Based Information Retrieval in HealthAgents

This paper focuses on the problem of representing, in a meaningful way, the knowledge involved in the HealthAgents project. Our work is motivated by the complexity of representing Electronic Health-care Records in a consistent manner. We present HADOM (HealthAgents Domain Ontology) which conceptualises the required HealthAgents information and propose describing the sources knowledge by the means of Conceptual Graphs (CGs). This allows to build upon the existing ontology permitting for modularity and °exibility. The novelty of our approach lies in the ease with which CGs can be placed above other formalisms and their potential for optimised querying and retrieval

Metagenes Associated with Survival in Non-Small Cell Lung Cancer

NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most