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.

The PiCT® test is a reliable alternative to the activated partial thromboplastin time in unfractionated heparin therapy management: results from a multicenter study.

Essentials Activated partial thromboplastin time (APTT) or anti-Xa tests are used to monitor heparin. Prothrombinase-induced Clotting Time (PiCT) was compared to APTT in a clinical study. PiCT shows higher correlation to anti-Xa than APTT does and is more comparable between centers. PiCT demonstrates significantly higher accuracy and reliability than APTT in heparin monitoring. SUMMARY: Background Unfractionated heparin (UFH) is still a commonly used anticoagulant for prevention and treatment of thromboembolism in a variety of situations. Increasingly, chromogenic anti-Xa assays are used for UFH monitoring given the high variability of the activated partial thromboplastin time (APTT) in this setting. On the other hand, and despite the known variability, the APTT test remains the most frequently used monitoring tool in UFH therapy because of its broad availability, lower costs and wide acceptance. Various guidelines continue to recommend the use of the APTT as an anti-Xa surrogate, but this approach remains controversial. Objective To assess the prothrombinase-induced clotting time (PiCT® ) test, reported in seconds, as an alternative to the APTT in the management of UFH-mediated anticoagulation. Methods Plasma samples from patients receiving UFH were obtained in three different centers in the USA and Europe. Samples were analyzed for PiCT, APTT and anti-Xa activities with conditions set to allow comparability. Target-ranges in seconds for PiCT and APTT were established for a UFH concentration of 0.3-0.7 IU mL-1 , derived from anti-Xa results as suggested by the ACCP guidelines. Results PiCT demonstrated better correlation with anti-Xa IU mL-1 than APTT, higher ability to identify samples within target range and, importantly, comparable target-ranges between different centers. Conclusion Accuracy and reliability of PiCT are significantly better than those of APTT in monitoring UFH for anticoagulant therapy.

The uncalibrated prothrombinase-induced clotting time test. Equally convenient but more precise than the aPTT for monitoring of unfractionated heparin.

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT's dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit®PiCT®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.

Risk factors for advanced lesions undetected at prior colonoscopy: not always poor preparation.

BACKGROUND AND STUDY AIM: Colonoscopy is regarded as the gold standard for diagnosis of colonic lesions. However, adenoma miss rates in tandem colonoscopy studies vary from 2 % to 26 %. We aimed to investigate the rates of advanced neoplasia in patients with a prior normal colonoscopy in an outpatient endoscopy unit. METHODS: Review of reports for colonoscopies performed in our Endoscopy Unit from 2000 to 2005. Undetected lesions were defined as advanced adenoma or colorectal cancer (CRC) not reported in a colonoscopy performed in the previous 2 or 3 years, respectively. Patients with hereditary nonpolyposis CRC (HNPCC) and familial adenomatous polyposis (FAP) were excluded. RESULTS: Between 2002 and 2005, 795 patients were diagnosed with at least one advanced adenoma and 386 with CRC. Among these, 107/795 patients (13.5 %) had advanced adenoma that had been undetected in a previous colonoscopy (39 % [53/135 lesions] in the right colon); 92/107 (86 %) had an undetected advanced adenoma ≥ 10 mm. Previously undetected CRCs were found in 27/386 patients (6.7 %), located in the left colon in 21/27 (78 %); in 7 the area had not been reached in the previous colonoscopy. Risk factors for undetected advanced adenoma were advanced age, male gender, the presence of another advanced adenoma at first colonoscopy, and history of advanced neoplasia. CONCLUSIONS: Failure to detect advanced neoplasia is common in a community-based endoscopy facility. Previously undetected advanced lesions are more frequently found in the left colon and rectum. Risk factors for non-detection of advanced adenoma are similar to those for advanced neoplasia recurrence. Lowering non-detection rates is crucial for correct follow-up recommendations. Patients should be aware of rates of detection of advanced neoplasia after previous normal colonoscopic findings.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity.

BACKGROUND: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity. METHODS: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology. RESULTS: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis. CONCLUSIONS: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

Aceleración secular de peso, talla e IMC. Estudios españoles transversales y longitudinales de crecimiento 2008 / Secular acceleration of weight, height and BMI. Cross-sectional and longitudinal Spanish studies on growth 2008

En España recientemente han finalizado estudios de crecimiento transversales que permiten evaluar la antropometría neonatal de recién nacidos prematuros y a término, y el crecimiento postnatal de niños y adolescentes. Además, disonemos de estudios longitudinales que permiten evaluar el crecimiento puberal diferenciado para cada grupo madurador. El peso y longitud al nacer fueron evaluados (1999-2002) en 9.362 recién nacidos, 26-42 semanas de edad gestacional, observándose dimorfismo sexual y un incremento en ambos parámetros respecto a estudios previos (1987-1992) particularmente en el grupo de recién nacidos pretérmino. El peso, talla e IMC fueron evaluados (2000-2004) en 32.064 niños y adolescentes (16.607 varones y 15.457 mujeres) de 0-24 años de edad, observándose aceleración secular en los tres parámetros respecto a estudios realizados hace 20 años. El incremento ponderal fue excesivo respecto al de talla, para los valores del IMC superiores al percentil 50. El estudio longitudinal (458 sujetos: 223 varones,235 mujeres, nacidos entre 1978 y 1982) permitió obtener patrones de crecimiento y de maduración puberal diferenciados para cada uno de los cinco grupos maduradores. La talla adulta en ambos estudios, es similar a la reportada en estudios europeos y americanos, aunque inferior a la alemana, sueca y holandesa. En varones el IMC fue superior al observado en países europeos y próximos al reportado en EE.UU. En mujeres el IMC fue similar al de países europeos e inferior al reportado en EE.UU (AU)

Cross-sectional and longitudinal growth studies have recently been conducted in Spain. Between 1999 and 2002, weight and vertex-heel length were evaluated in 9,362 new-borns (4,884 males, 4,478 females), 26-42 weeks of gestational age. Age increase in these values compared with previous Spanish studies (1987-1992) and sexual dimorphism were observed. Between 2000 and 204, height, weight and body mass index were evaluated in 32,064 subjects 816,607 males, 15,457 females) from birth to adulthood. A secular trend of growth was observed compared to data obtained 20 years ago, with a higher increase in BMI values above the 50 th percentile. A longitudinal growth study of 458 healthy subjects (223 boys, 235 girls) born between 1978 and 1982 yielded pubertal growth and maturity standards for each of the five pubertal maturity groups. Adult height was similar to that reported by European and American studies, but lower than that reported for German, Swedish and Netherlands populations. In males, BMI was higher than in other European population and near to the USA population. In females, BMI was similar to European populations and lower than in the USA population (AU)

Síndrome compartimental crónico por ejercicio con denervación glútea bilateral / Chronic compartment syndrome due to exercise with bilateral gluteal denervation

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Asbetosis pulmonar / No disponible

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Spanish growth studies 2008. New anthropometric standards.

Cross-sectional and longitudinal growth studies have recently been conducted in Spain. These studies have allowed neonatal anthropometry in premature and term neonates and postnatal growth in children and adolescents to be evaluated. Moreover, a longitudinal study that allows pubertal growth to be evaluated for distinct groups according to maturation has also been published. Between 1999 and 2002, birth weight and vertex-heel length were evaluated in 9,362 newborns (4,884 boys and 4,478 girls), with a gestational age of 26-42 weeks. An increase in these values compared with previous Spanish studies (1987-1992) and sexual dimorphism were observed. Between 2000 and 2004, height, weight and body mass index (BMI) were evaluated in 32,064 individuals (16,607 males, 15,457 females) aged 0-24 years. An increasing secular trend was observed compared with data obtained 20 years previously. Increases in BMI exceeded those in height for BMI values above the 50th percentile. A longitudinal growth study of 458 healthy individuals (223 boys, 235 girls) born between 1978 and 1982 yielded pubertal growth and maturity standards for each of the five pubertal maturity groups. In addition, data on skinfolds, bone mass and intellectual development from birth to adulthood were also provided. Adult height in both studies was similar to that reported by European and American studies, but was lower than that reported for German, Swedish and Dutch populations. In males, BMI was higher than in other European populations and was close to that of the US population. In females, BMI was similar to that in European populations and was lower than that in the US population.

Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett's oesophagus.

BACKGROUND: There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO). AIM: To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO. METHODS: A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student-t test and the U-Mann-Whitney test were used for quantitative and ordinal variables. RESULTS: Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed. CONCLUSIONS: The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis.

Investigación translacional en patología digestiva: del laboratorio a la clínica y viceversa beneficiario: el paciente / No disponible

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Estudio preliminar de mutaciones germinales en el gen MYH en población aragonesa con cáncer de colon / No disponible

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Age related differences in the strategies used by middle aged adults to solve a block design task.

In the present study, it was proposed to investigate the effects of aging on the strategies used to solve a block design task and to establish whether these strategies may be associated with differential patterns of ability. Two groups of subjects, 30 young adults (aged 20-35 years) and 30 middle-aged adults (aged 45-60 years) were set a computer version of the Kohs task and a battery of tests. An age-related decrease in fluid intelligence (Gf) and visual-spatial ability (Gv) was observed, along with the fact that most of the older subjects used a global strategy rather than a synthetic one. On the other hand, while continuing to use strategies of the analytic type, the older subjects looked more frequently at the model and scored high on crystallized intelligence (Gc). These findings are discussed from two different points of view: the theory of hierarchical stimuli and the hypothesis that metacognitive ability, which is thought to rely on Gc, may increase with age, and thus compensate for the loss of Gf and Gv.

Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis.

BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available.

Hiperplasia suprarrenal congénita: diagnóstico, tratamiento y evolución a largo plazo / Congenital adrenal hyperplasia: diagnosis, treatment and long-term outcome

La hiperplasia suprarrenal congénita incluye los trastornos hereditarios de la síntesis suprarrenal del cortisol. Se conoce 5 formas clínicas, el déficit de 21 hidroxilasa es la forma más frecuente. El déficit de 21 hidroxilasa se puede categorizar clínicamente en formas clásicas (pérdida salina y virilizante simple) y formas no clásicas (sintomáticas y asintomáticas/crípticas). El presente trabajo revisa los aspectos diagnósticos y terapéuticos de la hiperplasia suprarrenal congénita, con especial referencia al déficit de 21 hidroxilasa y su evolución a largo plazo. Durante los últimos 30 años se han producido avances importantes, tanto diagnósticos como terapéuticos, que han permitido disminuir notablemente la morbimortalidad y posibilitar que los pacientes alcancen la edad adulta. El tratamiento persigue disminuir la secreción de corticotropina (ACTH) y el hiperandrogenismo suprarrenal subyacente, y reemplazar lo más fisiológicamente posible el déficit de glucocorticoides y mineralocorticoides. El tratamiento clínico con frecuencia se ve complicado por fases de hiperandrogenismo inadecuadamente controlado y/o hipercortisolismo iatrogénico. En la evolución a largo plazo, estos pacientes pueden presentar una serie de complicaciones entre las que se incluyen baja talla, obesidad, disminución de la densidad mineral ósea, disfunción gonadal, infertilidad y disfunción psicosexual en las mujeres. En la actualidad existen nuevas pautas terapéuticas en fase de investigación entre las que se incluyen el uso de antiandrógenos, inhibidores de la síntesis de estrógenos y la adrenalectomía (AU)

COX-2 and colorectal cancer.

Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.

Basal ganglia and supplementary motor area subtend duration perception: an fMRI study.

Brain imaging studies on duration perception usually report the activation of a network that includes the frontal and mesiofrontal cortex (supplementary motor area, SMA), parietal cortex, and subcortical areas (basal ganglia, thalamus, and cerebellum). To address the question of the specific involvement of these structures in temporal processing, we contrasted two visual discrimination tasks in which the relevant stimulus dimension was either its intensity or its duration. Eleven adults had to indicate (by pressing one of two keys) whether they thought the duration or the intensity of a light (LED) was equal to (right hand) or different from (left hand) that of a previously presented standard. In a control task, subjects had to press one of the two keys at random. A similar broad network was observed in both the duration-minus-control and intensity-minus-control comparisons. The intensity-minus-duration comparison pointed out activation in areas known to participate in cognitive operations on visual stimuli: right occipital gyrus, fusiform gyri, hippocampus, precuneus, and intraparietal sulcus. In contrast, the duration-minus-intensity comparison indicated activation of a complex network that included the basal ganglia, SMA, ventrolateral prefrontal cortex, inferior parietal cortex, and temporal cortex. These structures form several subnetworks, each possibly in charge of specific time-coding operations in humans. The SMA and basal ganglia may be implicated in the time-keeping mechanism, and the frontal-parietal areas may be involved in the attentional and mnemonic operations required for encoding and retrieving duration information.