Targeted transcriptomic analysis of pancreatic adenocarcinoma in EUS-FNA samples by NanoString technology.

Background: Integration of transcriptomic testing into EUS-FNA samples is a growing need for precision oncology in pancreatic ductal adenocarcinoma (PDAC). The NanoString platform is suitable for transcriptome profiling in low yield RNA samples. Methods: Inclusion of patients that underwent EUS-FNA cytological diagnosis of pancreatic ductal adenocarcinoma using 19G and/or 22G needles and subsequent surgical resection. Formalin-fixed, paraffin-embedded (FFPE) cytological and surgical samples underwent RNA extraction and transcriptomic analysis using a custom 52-gene NanoString panel of stromal PDAC features. Cell type abundance was quantified in FFPE specimens and correlated. Results: 18 PDAC patients were included. Mean EUS-FNA passes was 2 + 0.7. All FFPE passed the RNA quality control for genomic analysis. Hierarchical clustering on the global gene expression data showed that genes were differentially expressed between EUS and surgical samples. A more enriched cancer-associated fibroblasts and epithelial-mesenchymal transition transcriptomic profile was observed across surgical specimens whereas immunological biomarkers were more represented in EUS-FNA samples. Cytological examination confirmed a scanty representation of CAF and more immunological cell abundance in cytological samples in comparison to surgical specimens. Conclusion: Targeted transcriptomic NanoString profiling of PDAC samples obtained by EUS-FNA is a feasible approach for pre-surgical molecular analysis although stromal CAF/EMT mRNA biomarkers are underrepresented.

Telemedicine and intraductal papillary mucinous neoplasms: Analysis of a new follow-up strategy during COVID-19 outbreak.

BACKGROUND: The Coronavirus pandemic outbreak in 2019 and the saturation of healthcare system led to an increased use of digital tools for surveillance. In this study we described our experience using telemedicine to follow-up on patients with intraductal papillary mucinous neoplasms during the COVID-19 era and analyze those factors associated to patients' satisfaction. METHODS: This 1-year retrospective observational study enrolled patients with intraductal papillary mucinous neoplasms followed-up by telemedicine during COVID-19 outbreak. Patients with high-risk features needing on-site physical examination or declining remote follow-up were excluded. A 13-question survey was conducted; demographic, geographic, and employment information was collected. Univariate and multivariate analyses were performed to evaluate those factors associated to patients' satisfaction. RESULTS: Out of 287, a total of 177 patients with intraductal papillary mucinous neoplasms were included: the mean age was 69 (44-87) years and the male/female ratio was 0.78. A total of 80 (45.2%) patients had previously experienced abdominal pain. Most patients (85.3%) were satisfied with telemedicine: at univariate analysis, age ≥70 years (P = .007), retirement (P = .001), and absence of previous abdominal pain (P = .05) were significantly associated with patient satisfaction. At multivariate analysis, the absence of previous abdominal pain was the only factor independently associated with patient satisfaction (odds ratio 5.964, 95% confidence interval 2.21-16.11, P < .001). CONCLUSION: Telemedicine allows a new follow-up strategy that can be used in selected patients with intraductal papillary mucinous neoplasms. The absence of previous abdominal pain is associated with patient satisfaction during follow-up. Further studies are needed to evaluate safety of remote follow-up in patients with intraductal papillary mucinous neoplasms.

Procedures and recommended times in the care process of the patient with pancreatic cancer: PAN-TIME consensus between scientific societies

Purpose. Pancreatic cancer (PC) is a disease with bad prognosis. It is usually diagnosed at advanced stages and its treatment is complex. The aim of this consensus document was to provide recommendations by experts that would ameliorate PC diagnosis, reduce the time to treatment, and optimize PC management by interdisciplinary teams. Methods. As a consensus method, we followed the modified Delphi methodology. A scientific committee of experts provided 40 statements that were submitted in two rounds to a panel of 87 specialists of 12 scientific societies. Results. Agreement was reached for 39 of the 40 proposed statements (97.5%). Conclusions. Although a screening of the asymptomatic population is not a feasible option, special attention to potential symptoms during primary care could ameliorate early diagnostic. It is especially important to decrease the period until diagnostic tests are performed. This consensus could improve survival in PC patients by decreasing the time to diagnose and time to treatment and by the implementation of multidisciplinary teams (AU)

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Procedures and recommended times in the care process of the patient with pancreatic cancer: PAN-TIME consensus between scientific societies.

PURPOSE: Pancreatic cancer (PC) is a disease with bad prognosis. It is usually diagnosed at advanced stages and its treatment is complex. The aim of this consensus document was to provide recommendations by experts that would ameliorate PC diagnosis, reduce the time to treatment, and optimize PC management by interdisciplinary teams. METHODS: As a consensus method, we followed the modified Delphi methodology. A scientific committee of experts provided 40 statements that were submitted in two rounds to a panel of 87 specialists of 12 scientific societies. RESULTS: Agreement was reached for 39 of the 40 proposed statements (97.5%). CONCLUSIONS: Although a screening of the asymptomatic population is not a feasible option, special attention to potential symptoms during primary care could ameliorate early diagnostic. It is especially important to decrease the period until diagnostic tests are performed. This consensus could improve survival in PC patients by decreasing the time to diagnose and time to treatment and by the implementation of multidisciplinary teams.

Chronic diarrhoea: Definition, classification and diagnosis / Diarrea crónica: definición, clasificación y diagnóstico

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

La diarrea crónica es un síntoma de presentación frecuente, tanto en las consultas de medicina de familia como en las de digestivo. Se estima que >5% de la población sufre diarrea crónica y que cerca del 40% de estos sujetos son mayores de 60 años. El clínico se enfrenta con frecuencia a la necesidad de decidir cuál es el mejor enfoque diagnóstico de estos pacientes y elegir entre las múltiples pruebas diagnósticas existentes. En 2014 la Societat Catalana de Digestologia creó un grupo de trabajo con el objetivo principal de crear algoritmos diagnósticos en base a la práctica clínica y evaluar las pruebas diagnósticas disponibles y la evidencia científica para su utilización. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Se han establecido 28 recomendaciones y 6 algoritmos diagnósticos. Se describen los criterios de derivación desde medicina primaria a digestivo de un paciente con diarrea crónica.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

ZEB1 represses E-cadherin and induces an EMT by recruiting the SWI/SNF chromatin-remodeling protein BRG1.

Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadherin gene at the transcriptional level. In this study, we show that ZEB1 interacts with the SWI/SNF chromatin-remodeling protein BRG1 to regulate E-cadherin independently of CtBP, its traditional co-repressor. Blocking the interaction between ZEB1 and BRG1 induces expression of E-cadherin and downregulation of the mesenchymal marker vimentin. ZEB1 and BRG1 colocalize in E-cadherin-negative cells from cancer lines and in the stroma of normal colon. Colocalization of ZEB1 and BRG1 in epithelial cells is only found in those de-differentiated cells characterized by nuclear beta-catenin staining at the invasive edge of the tumor. Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.

Shock séptico por Streptococcus bovis en paciente en hemodiálisis / No disponible

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Abnormal ERPs and high frequency bands power in multiple sclerosis.

Event-related potentials (ERPs) and power spectral density (PSD) were registered during an auditory-oddball paradigm in 11 MS patients. These patients showed a decrease in the amplitude of P2 and N2 components and a delayed P3 latency compared to control subjects suggesting that the attentional orienting mechanism in the auditory modality is affected in MS. The PSD analysis showed that MS patients exhibited an increased power in beta and gamma bands. The combined analysis of frequency and time domain suggested diverse phenomena that occurred in the MS patient group related with the EEG background or the motivational status.

Alternate response preparation in a visuomotor serial task.

The preparation of a particular motor pattern is related to the information available that enables the actor to predict the correct response to a forthcoming stimulus. In many situations, however, prediction is not possible. In such cases, the individual can guess the probable parameters of the next stimulus. The authors attempted to establish the bias in the motor intention for movement and its interaction with a possible memory trace of the stimulus-response mapping produced by the preceding stimulus. Two letters were presented bilaterally, and participants (N=21) had to discriminate the target letter and respond with the compatible hand. The present findings support the existence of a memory trace of the previous stimulus-response mapping.

Gender differences in event-related potentials during visual-spatial attention.

The aim of present work is to test possible gender differences in the ERPs to the standards during the performance of a visual-spatial attention task. The sample: 20 subjects (10 women) aged 18-24. Electrodes: F3, F4, C3, C4, P3, P4, T5, T6, O1, O2. ANOVA tests were computed with the following factors: attention, gender, visual field, hemisphere, and electrodes. Results showed that men presented higher amplitudes in P1 and in P3b than did women, and women presented higher amplitudes in the temporal N1 than did men. For the P3, the amplitude in frontal-central regions for the attended condition was higher in men than in women, and men presented a gender-specific right frontal functional asymmetry that was not present in women. Since these components are related with the modulation of visual processing by the effect of spatial attention, the intra- and inter-gender differences obtained suggest possible differences in the processing of visual information in both genders. However, the fact that the brain generators could have a different orientation is also a possible explanation for the differences obtained in the ERPs in both genders.

Further improvements in the application of high-performance liquid chromatography, capillary electrophoresis and capillary electrochromatography to the analysis of algal toxins in the aquatic environment.

The presence of algal toxins in the aquatic environment represents an important socioeconomic concern in many places worldwide, due to the toxicity that these compounds can induce in seafood or freshwater organisms at very low levels. Several analytical alternatives have been proposed over the last years for the control of these contaminants, which acute or chronic toxicity requires low detection levels and demands for the search of sensitive methods for their detection and determination. HPLC has been widely used for this purpose, although several alternatives such as CE or capillary electrochromatography (CEC) are being lately developed with this aim. In this work we report on the application of improved HPLC, as well as CE and CEC, for the analysis of diarrhetic shellfish poisoning toxins, amnesic shellfish poisoning (ASP) toxins and microcystins (MCs) present in different matrices such as water, shellfish or algae. Improvements in sample preparation for increasing sensitivity and selectivity are also shown. While UV and fluorimetric detection are the detection methods generally used, mass spectrometric detection was also applied for ASP toxins and MCs, especially for confirmatory purposes. From the results obtained it can be concluded that both HPLC and CE offer a good potential for a sensitive and selective determination of these algal toxins in such complex matrices. The results obtained for CEC allow also to conclude that this technique can result in a promising technique for such application.

Sensory and motor attentional modulation during the manual gap effect in humans: a high-density ERP study.

The present study investigated reaction time (RT) and event-related potential (ERP) differences between gap and step conditions using visual stimulation and manual responses. RTs during the gap condition were facilitated with respect to those of the step condition. The ERPs, which were obtained from electrodes placed at 58 scalp sites, showed differences when the gap and step conditions were compared for the following components: an early positive component centred at the vertex, an enhanced P1 component, a frontal negativity, a negative lateralized motor potential, and an increased P3. All these results suggest that the facilitation induced by the gap is mediated by a modulation of the neural circuits involved in sensory, motor, and cognitive functions.

[Temporal spectral evolution of electroencephalogram. Methodology and applications]. / Dinámica temporal de la frecuencia del electroencefalograma. Metodología y aplicaciones.

INTRODUCTION: The event related potentials (ERPs) allow to study the evolution of the cerebral electric activity related with the diverse sensorial, motors and cognitive processes. However, the ERPs and the spectral analyses based in Fast Fourier Transform, are not able to show the variations along the time of the spectral content of the electroencephalogram (EEG). OBJECTIVE: The present work will show the necessary methodology to obtain the temporal dynamics of the frequency (TSE) in the EEG, a technique described by Salmelin and Hari (1994) that allows the analysis of the modulations of any spectral band along the time. SUBJECTS AND METHODS: The presented data correspond to the electroencephalographic registration of 20 human subjects during an experiment of visual spatial attention. RESULTS: The modulations of the ERPs differ of the observed by the spectral techniques in latency and topography. Likewise, comparing different spectral techniques is proven that the TSE allows to define with more temporal precision the variations on the spectral content. CONCLUSION: The application of the TSE technique to the same EEG signal that is used for obtaining the ERPs, allows the inclusion of the variable time in the spectral analysis of the EEG, what can be crucial to understand the physiological bases of some neuropathologies.

Temporal evolution of alpha and beta bands during visual spatial attention.

Event-related potentials (ERPs) are an electrophysiological index of various cognitive processes such as attention. However, this kind of analysis does not allow observation of differences in the spectral content taking place during a sensory, cognitive or motor task. The goal of the present work was to compute the temporal dynamics of EEG oscillations using a technique called temporal spectral evolution (TSE). The electroencephalogram (EEG) was recorded during the presentation of flashed stimuli that were randomly presented to the left or right visual field. Subjects were asked to pay attention, alternately in different blocks of trials, to the left or to the right to detect an infrequent target. The results showed a decrease in the alpha band in a time window of 375-500 ms and an increase in the beta band at 500-875 ms after stimulus onset, for both attended and unattended stimuli. Statistical analysis showed that the decrease in alpha and the increase in beta were more marked during the attentional condition. In conclusion, these results demonstrate that the decrease in alpha band and the increase in beta band are electrophysiological markers of visual spatial attention.