The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

Mental health and COVID-19 in a general population cohort in Spain (COVICAT study).

PURPOSE: Mental health conditions may affect outcome of COVID-19 disease, while exposure to stressors during the pandemic may impact mental health. The purpose of this study was to examine these factors in relation to ocurrence of depression and anxiety after the first outbreak in Spain. METHODS: We contacted 9515 participants from a population-based cohort study in Catalonia between May and October 2020. We drew blood samples to establish infection to the virus. Pre-pandemic mental health conditions were confirmed through Electronic Health Registries. We used the Hospital Anxiety and Depression Scale to assess severe depression and anxiety post-pandemic. Exposure to proximal, financial and wider environment stressors during the lockdown were collected. We calculated Relative Risks (RR), adjusting for individual- and contextual covariates. RESULTS: Pre-pandemic mental health disorders were not associated with SARS-CoV-2 infection , but were associated with severity of COVID-19 disease. People with pre-existing mental health disorders showed higher prevalence of severe depression (25.4%) and anxiety (37.8%) than those without prior mental disorders (4.9% and 10.1%). Living alone was a strong predictor of severe depression among mental health patients (RR = 1.6, 95% CI 1.2-2.2). Among those without prior mental health disorders, post-lockdown depression and anxiety were associated with household interpersonal conflicts (RR = 2.6, 95% CI 2.1-3.1; RR = 2.1, 95% CI 1.9-2.4) and financial instability (RR = 2.2, 95% CI 1.8-2.9; 1.9, 95% CI 1.6-2.2). CONCLUSIONS: The COVID-19 pandemic and the lockdown were associated with increased post-lockdown depression and anxiety. Patients with pre-existing mental health conditions are a vulnerable group for severe COVID-19 disease.

A multi-technique approach to understanding delithiation damage in LiCoO2 thin films.

We report on the delithiation of LiCoO2 thin films using oxalic acid (C2H2O4) with the goal of understanding the structural degradation of an insertion oxide associated with Li chemical extraction. Using a multi-technique approach that includes synchrotron radiation X-ray diffraction, scanning electron microscopy, micro Raman spectroscopy, photoelectron spectroscopy and conductive atomic force microscopy we reveal the balance between selective Li extraction and structural damage. We identify three different delithiation regimes, related to surface processes, bulk delithiation and damage generation. We find that only a fraction of the grains is affected by the delithiation process, which may create local inhomogeneities. However, the bulk delithiation regime is effective to delithiate the LCO film. All experimental evidence collected indicates that the delithiation process in this regime mimics the behavior of LCO upon electrochemical delithiation. We discard the formation of Co oxalate during the chemical extraction process. In conclusion, the chemical route to Li extraction provides additional opportunities to investigate delithiation while avoiding the complications associated with electrolyte breakdown and simplifying in-situ measurements.

SEOM clinical guidelines for pancreatic and biliary tract cancer (2020)

Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3–4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC (AU)

SEOM clinical guidelines for pancreatic and biliary tract cancer (2020).

Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3-4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.

A Novel Computerized Cognitive Stress Test to Detect Mild Cognitive Impairment.

BACKGROUND: The Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) is a novel and increasingly employed instrument that has outperformed widely used cognitive measures as an early correlate of elevated brain amyloid and neurodegeneration in prodromal Alzheimer's Disease (AD). The LASSI-L has distinguished those with amnestic mild cognitive impairment (aMCI) and high amyloid load from aMCI attributable to other non-AD conditions. The authors designed and implemented a web-based brief computerized version of the instrument, the LASSI-BC, to improve standardized administration, facilitate scoring accuracy, real-time data entry, and increase the accessibility of the measure. OBJECTIVE: The psychometric properties and clinical utility of the brief computerized version of the LASSI-L was evaluated, together with its ability to differentiate older adults who are cognitively normal (CN) from those with amnestic Mild Cognitive Impairment (aMCI). METHODS: After undergoing a comprehensive uniform clinical and neuropsychological evaluation using traditional measures, older adults were classified as cognitively normal or diagnosed with aMCI. All participants were administered the LASSI-BC, a computerized version of the LASSI-L. Test-retest and discriminant validity was assessed for each LASSI-BC subscale. RESULTS: LASSI-BC subscales demonstrated high test-retest reliability, and discriminant validity was attained. CONCLUSIONS: The LASSI-BC, a brief computerized version of the LASSI-L is a valid and useful cognitive tool for the detection of aMCI among older adults.

Amnestic Mild Cognitive Impairment is Characterized by the Inability to Recover from Proactive Semantic Interference across Multiple Learning Trials.

BACKGROUND: Difficulties in inhibition and self-monitoring are early features of incipient Alzheimer's disease and may manifest as susceptibility to proactive semantic interference. However, due to limitations of traditional memory assessment paradigms, recovery from interference effects following repeated learning opportunities has not been explored. OBJECTIVE: This study employed a novel computerized list learning test consisting of repeated learning trials to assess recovery from proactive and retroactive semantic interference. DESIGN: The design was cross-sectional. SETTING: Participants were recruited from the community as part of a longitudinal study on normal and abnormal aging. PARTICIPANTS: The sample consisted of 46 cognitively normal individuals and 30 participants with amnestic mild cognitive impairment. MEASUREMENTS: Participants were administered the Cognitive Stress Test and traditional neuropsychological measures. Step-wise logistic regression was applied to determine which Cognitive Stress Test measures best discriminated between diagnostic groups. This was followed by receiver operating characteristic analyses. RESULTS: Cued A3 recall, Cued B3 recall and Cued B2 intrusions were all independent predictors of diagnostic status. The overall predictive utility of the model yielded 75.9% sensitivity, 91.1% specificity, and an overall correct classification rate of 85.1%. When these variables were jointly entered into receiver operating characteristic analyses, the area under the curve was .923 (p<.001). CONCLUSIONS: This novel paradigm's use of repeated learning trials offers a unique opportunity to assess recovery from proactive and retroactive semantic interference. Participants with mild cognitive impairment exhibited a continued failure to recover from proactive interference that could not be explained by mere learning deficits.

Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population.

Multimorbidity is an emerging topic in public health policy because of its increasing prevalence and socio-economic impact. However, the age- and gender-dependent trends of disease associations at fine resolution, and the underlying genetic factors, remain incompletely understood. Here, by analyzing disease networks from electronic medical records of primary health care, we identify key conditions and shared genetic factors influencing multimorbidity. Three types of diseases are outlined: "central", which include chronic and non-chronic conditions, have higher cumulative risks of disease associations; "community roots" have lower cumulative risks, but inform on continuing clustered disease associations with age; and "seeds of bursts", which most are chronic, reveal outbreaks of disease associations leading to multimorbidity. The diseases with a major impact on multimorbidity are caused by genes that occupy central positions in the network of human disease genes. Alteration of lipid metabolism connects breast cancer, diabetic neuropathy and nutritional anemia. Evaluation of key disease associations by a genome-wide association study identifies shared genetic factors and further supports causal commonalities between nervous system diseases and nutritional anemias. This study also reveals many shared genetic signals with other diseases. Collectively, our results depict novel population-based multimorbidity patterns, identify key diseases within them, and highlight pleiotropy influencing multimorbidity.

SEOM clinical guideline on unknown primary cancer (2017)

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors (AU)

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SEOM clinical guideline on unknown primary cancer (2017).

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors.

Biomarkers in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice (AU)

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Biomarkers in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is currently the third most frequent form of malignancy. The role of biomarkers in the diagnostic and therapeutic strategy of cancer is constantly expanding. Translational research is already changing paradigms in tumours encompassing from early diagnosis to precision medicine in advanced disease. Nomenclature for molecular subtypes of tumours is gradually gaining acceptance and there are growing expectations it will further go from the bench to the bedside. However, the clinical relevance of biomarkers in PDAC is still far behind the relevance of biomarkers in other solid tumours. This article is part of a wider project (GALLgo) involving over forty specialists devoted to the multidisciplinary management of PDAC which concluded in recommendations based on scientific evidence. The aim of the present article is to review the diagnostic, prognostic and predictive biomarkers, either in localised or advanced disease, which have been lately subjected to study and analysis and others currently available for PDAC in order to give strength-graded recommendations linked to quality of evidence that can be used as guidelines in routine clinical practice.

Activity of weekly paclitaxel-cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors.

BACKGROUND: Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs). METHODS: Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2). RESULTS: 148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31-11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88-8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS. CONCLUSIONS: WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS.

Detección de cortisol salival nocturno en una muestra de sujetos de Santiago de Chile, mediante la técnica deelectroquimioluminicencia / Night salivary cortisol measurement in a sample of volunteers from Santiago using an electroquimioluminicence technique

Cortisol is a glucocorticoid hormone with circadian cycle, it shows high levels in the morning and lower in the night. The salivary cortisol is the biologically active fraction and night measurement has been very useful for improving the diagnosis of Cushing’s syndrome, an endocrine disorder characterized by high levels of cortisol and loss of their circadian cycle. A disadvantage of this measurement is the establishment of reference ranges, which depends on the population and technique. Therefore the night salivary cortisol values were determined in a sample of 75 healthy volunteers, aged 18-75 years old. Each volunteer collects two samples in consecutive days and these samples were analyzed by electrochemiluminescence. The average of night salivary cortisol of volunteers was 0.165 +/- 0.059 ug/dL with a range from 0.082 to 0.352 ug/dL and no significant differences were found between two samples of cortisol in day 1 and 2. Our results suggest that the proposed cut-off limit 0.32 ug/dL between patients with and without Cushing Syndrome would be suitable for this technique and in our population.

Queratoplastia endotelial automatizada con pelado de membrana de Descemet (DSAEK). Revisión sistemática sobre efectividad y seguridad / Descemet's stripping automated endothelial keratoplasty (DEAEK). Systematic review of clinical-effectiveness and safety

OBJETIVOS: Realizar una revisión sistemática sobre la eficacia/efectividad, seguridad y costes de la queratoplastia endotelial automatizada con pelado de la membrana de Descemet (DSAEK) en pacientes con fracaso endotelial corneal. MÉTODO: Búsqueda exhaustiva de la bibliografía en las principales bases de datos biomédicas entre enero y mayo de 2012. RESULTADOS: De 485 artículos localizados se incluyeron 16 series de casos y un estudio de coste-efectividad. Se observó una mejoría tras la intervención en la agudeza visual corregida y sin corregir, alcanzándose valores de 0,6 a 0,8 y de 0,5 respectivamente. El astigmatismo no fue significativo en relación con los valores basales. Las principales complicaciones fueron la dislocación-desprendimiento del injerto (1,5-23%), el fracaso primario (0-12%) y el rechazo endotelial (0,8-8,5%). CONCLUSIONES: En la distrofia de Fuchs y en la queratopatía bullosa, la DSAEK mejora la agudeza visual corregida y sin corregir en relación con los valores preintervención. El astigmatismo originado tras la DSAEK no fue significativo. Las complicaciones más importantes están relacionadas con la viabilidad del injerto, siendo la más frecuente la dislocación-desprendimiento y en menor medida el rechazo endotelial. Los estudios que evalúan la DSAEK son series de casos, en su mayoría retrospectivas. La calidad de este tipo de trabajos no es elevada y presenta limitaciones

OBJECTIVE: To conduct a systematic review of the efficacy/effectiveness, safety and cost of Descemet's stripping automated endothelial keratoplasty (DSAEK) technique in patients with corneal endothelial failure. METHODS: Comprehensive literature search conducted in the main biomedical databases from January-May 2012. RESULTS: Following a critical perusal of the total of 485 abstracts retrieved, 16 case series and one economic evaluation study were included. Corrected distance visual acuity and uncorrected distance visual acuity improved after treatment with DSAEK, attaining values of 0.6 to 0.8 and 0.5 respectively. The degree of post-DSAEK astigmatism was not significant with respect to baseline values. The main complications were graft dislocation-detachment (1.5-23%), primary failure (0-12%) and endothelial rejection (0.8-8.5%). CONCLUSIONS: In Fuchs' dystrophy and bullous keratopathy, data on the effectiveness of DSAEK indicate post-intervention improvement in uncorrected and corrected distance visual acuity. Astigmatism arising after DSAEK was not significant. The most significant post-DSAEK complications are linked to the viability of the graft, with the most frequent complications being dislocation-detachment and, to a lesser extent, endothelial rejection. The studies that assess DSAEK are case series, and for the most part retrospective. The quality of this type of studies is both low and limited

[Descemet's stripping automated endothelial keratoplasty (DEAEK). Systematic review of clinical-effectiveness and safety]. / Queratoplastia endotelial automatizada con pelado de membrana de Descemet (DSAEK). Revisión sistemática sobre efectividad y seguridad.

OBJECTIVE: To conduct a systematic review of the efficacy/effectiveness, safety and cost of Descemet's stripping automated endothelial keratoplasty (DSAEK) technique in patients with corneal endothelial failure. METHODS: Comprehensive literature search conducted in the main biomedical databases from January-May 2012. RESULTS: Following a critical perusal of the total of 485 abstracts retrieved, 16 case series and one economic evaluation study were included. Corrected distance visual acuity and uncorrected distance visual acuity improved after treatment with DSAEK, attaining values of 0.6 to 0.8 and 0.5 respectively. The degree of post-DSAEK astigmatism was not significant with respect to baseline values. The main complications were graft dislocation-detachment (1.5-23%), primary failure (0-12%) and endothelial rejection (0.8-8.5%). CONCLUSIONS: In Fuchs' dystrophy and bullous keratopathy, data on the effectiveness of DSAEK indicate post-intervention improvement in uncorrected and corrected distance visual acuity. Astigmatism arising after DSAEK was not significant. The most significant post-DSAEK complications are linked to the viability of the graft, with the most frequent complications being dislocation-detachment and, to a lesser extent, endothelial rejection. The studies that assess DSAEK are case series, and for the most part retrospective. The quality of this type of studies is both low and limited.

Large negative thermal expansion of the Co subnetwork measured by EXAFS in highly disordered Nd1-xCox thin films with perpendicular magnetic anisotropy.

We have measured a negative thermal expansion (NTE) of the Co subnetwork in amorphous Nd1-xCox (0.78 < x < 0.84) thin films of the order of 1% in volume using linearly polarized EXAFS spectroscopy at RT and 10 K. The expansion, which is anisotropic, is uncorrelated with the perpendicular magnetic anisotropy (PMA) observed in all the films, but correlated with the method used to deposit them. The atomic environments of the Nd atoms resulted in such a strong disorder that Nd-Nd and Nd-Co environments were invisible to EXAFS, and only Co-Co atomic environments were detected. The information on the Nd subnetwork was obtained through its magnetic moment measured by XMCD. These measurements demonstrate an increasing interaction of neodymium atoms with their particular local crystal field as the temperature decreased, suggesting possible structural modifications at their sites. Since the magnetic moment of the cobalt subnetwork remains essentially constant with the temperature, it is proposed that its detected NTE may be caused by the mechanical response of the amorphous network to structural transformations at the Nd sites. These results support that the PMA in RE-TM alloys is localized at the RE sites. The complete absence of EXAFS oscillations in the Nd L3 EXAFS spectra is remarkable: it means that the coherence length of the photoemitted electrons in disordered matter can be strongly reduced from that expected by atomic calculations to the point of being less than first neighbor distances, which is contrary to the common belief that first neighbors are always visible by EXAFS.

Topological defects and misfit strain in magnetic stripe domains of lateral multilayers with perpendicular magnetic anisotropy.

Stripe domains are studied in perpendicular magnetic anisotropy films nanostructured with a periodic thickness modulation that induces the lateral modulation of both stripe periods and in-plane magnetization. The resulting system is the 2D equivalent of a strained superlattice with properties controlled by interfacial misfit strain within the magnetic stripe structure and shape anisotropy. This allows us to observe, experimentally for the first time, the continuous structural transformation of a grain boundary in this 2D magnetic crystal in the whole angular range. The magnetization reversal process can be tailored through the effect of misfit strain due to the coupling between disclinations in the magnetic stripe pattern and domain walls in the in-plane magnetization configuration.

Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC).

Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies and a new generation of tyrosine kinase inhibitors, have been shown in phase II trials to be safe and effective in the treatment of advanced hepatocellular carcinoma. Several currently active phase III trials are testing these drugs, both in first- and second-line settings. Strategies to overcome primary and acquired resistance to antiangiogenic therapy are urgently needed. Novel biomarkers may help in improving the efficacy of drugs targeting angiogenesis.