Early evolutionary divergence between papillary and anaplastic thyroid cancers.

Background: Papillary thyroid cancer (PTC) is the most common thyroid carcinoma and exhibits an almost uniformly good prognosis, while anaplastic thyroid cancer (ATC) is less frequent and is one of the most aggressive cancers usually resistant to conventional treatment. Current hypothesis posits that ATC derives from PTC through the progressive acquisition of a discrete number of genomic alterations and implies that the mutational landscape of ATC resembles that of PTC. However, the clinical behaviour of ATC and PTC is radically different. We decided to address the disconnection between the clinical behaviour of ATC and PTC and the proposed model of the progressive development of ATC from PTC. Patients and methods: We carried out exome sequencing of DNA from 14 ATC specimens including three cases of concomitant ATC and PTC as well as their corresponding normal DNA from 14 patients. The sequencing results were validated using droplet digital PCR. We carried out immunohistochemistry and immunofluorescence studies of the concomitant ATC and PTC cases. In addition, we integrated our sequencing results with the existing TCGA data. Results: Most of the somatic mutations identified in the ATC component differed from the ones in PTC in the cases of concomitant ATC and PTC. The trunks of the phylogenetic trees representing the somatic mutations were short with long branches. In one case of concomitant PTC and ATC specimens, we observed an infiltration of PTC cells within the ATC component. Moreover, we integrated our results with data obtained from TCGA and observed that the most frequent mutations found in ATC presented high cancer cell fraction values and were significantly different from the PTC ones. Conclusion: ATC diverge from PTC early in tumour development and both tumour types evolve independently. Our work allows the understanding of the relationship between ATC and PTC facilitating the clinical management of these malignancies.

Determination of soluble ultra-trace metals and metalloids in rainwater and atmospheric deposition fluxes: a 2-year survey and assessment.

The present work investigates the relationships between composition of rainwater and dry deposition fluxes by trace metals and metalloids. A modification in automatic "wet-only" and "dry-only" samplers was applied, which allowed the collection and conservation of samples separately. ICP-MS technique was used for the determination of analytes in samples. Concentrations of soluble elements in rainwater were measured directly in filtered samples. A sequential acid treatment with nitric, hydrofluoric and finally perchloric acids was used to measure the total contents of metals and metalloids in coarse particles. Variation between periods of heavy and light rains was assessed. Almost all of the metals and metalloids - B, Tl, Th, U, Al, Cs, Be, Ti and others - studied in dry deposition showed important decreases in concentrations (40-92%) during periods of heavy rainfall. Most of these metals and metalloids - As, Cr, Co, Ni - presented their highest levels (53-90%) in heavy rainfall periods in rainwater samples. Sources were identified in both types of samples collected using a new chemometric tool (SPCA). Urban traffic, surrounding contaminated soils and local anthropogenic sources were identified for rainwater samples. Natural and contaminated soils and general anthropogenic emissions were the sources identified for dry deposition fluxes.

Rediscovering contact inhibition in the embryo.

The cellular reaction called contact inhibition of locomotion was initially characterised by Michael Abercrombie more than 60 years ago. In his most general definition, it is defined as the stopping of the continued locomotion of a cell in the direction which has produced a collision with another cell. This deceptively simple response has been widely studied in vitro in a number of cell types over the years, yet it is still often misunderstood by the scientific community. Abercrombie spent much of his life studying the failure of the response shown by cancer cell types and how this might lead to malignant invasion of normal tissue. However, since Abercrombie's time, a role for this response in living organisms has been left to the realm of speculation. Here, we discuss the history of contact inhibition research, clarify some of the misconceptions about the response and reclaim misused terminology. We will also highlight our recent work, which for the first time elucidates a functional role for contact inhibition in vivo during embryogenesis.

Short-term outcome of psychogenic non-epileptic seizures after communication of the diagnosis.

We previously described a communication strategy for the delivery of the diagnosis of psychogenic non-epileptic seizures (PNES) that was acceptable and effective at communicating the psychological cause of PNES. This prospective multicenter study describes the short-term seizure and psychosocial outcomes after the communication of the diagnosis and with no additional treatment. Participants completed self-report measures at baseline, two and six months after the diagnosis (seizure frequency, HRQoL, health care utilization, activity levels, symptom attributions and levels of functioning). Thirty-six participants completed the self-report questionnaires. A further eight provided seizure frequency data. After six months, the median seizure frequency had dropped from 10 to 7.5 per month (p=0.9), 7/44 participants (16%) were seizure-free, and an additional 10/44 (23%) showed greater than 50% improvement in seizure frequency. Baseline questionnaire measures demonstrated high levels of impairment, which had not improved at follow-up. The lack of change in self-report measures illustrates the need for further interventions in this patient group.

Attention deficit hyperactivity disorder increases the risk of having abnormal eating behaviours in obese adults.

OBJECTIVE: To determine the rate of abnormal eating behaviours in obese adult patients with attention deficit hyperactivity disorder (ADHD) in comparison with obese adult patients without ADHD. METHOD: This case-control study includes: obese adult patients defined by a body mass index (BMI) ≥30 kg/m², screening positive in the adult ADHD self-report scale-V1.1. (ASRS-V1.1), attending the Nutrition Section, as cases; and obese adult patients screening negative, as controls. Weight, height and BMI were determined in all the participants. The rate of abnormal eating behaviours was determined using an eating pattern questionnaire. RESULTS: Forty-five out of 51 (88.2%) cases vs 127 out of 179 (70.9%) controls had abnormal eating behaviours (p=0.01). Eating between-meal snacks was found in 39 (76.5%) cases vs 107 (59.8%) controls (p=0.03), going on binge eating episodes in 28 (54.9%) vs 42 (23.5%) (p=0.00), waking up at night to eat in 11 (21.6%) vs 16 (8.9%) (p=0.01), eating large amounts of food in 13 (25.5%) vs 38 (21.2%) (p=0.52), and eating in secret in 11 (21.6%) vs 16 (8.9%) (p=0.01), respectively. CONCLUSION: This is the first study that determines the rate of these abnormal eating behaviours in obese adult patients with ADHD in comparison with obese adult patients without ADHD. A high rate of abnormal eating behaviours was observed in obese patients with ADHD. Our results suggest that ADHD is a risk factor for the development of these abnormal eating behaviours, which may be contributing factors of obesity and the unsuccessful treatment of obese patients.

Triple terapia en diabetes tipo 2: revisión sistemática de la evidencia disponible / Triple therapy in type 2 diabetes: systematic review of the available evidence

Las guías terapéuticas actuales difieren en las recomendaciones para la triple terapia cuando no se consiguen los objetivos con el tratamiento combinado dedos agentes orales. También difieren en el tipo de asociación y en la denominación de triple terapia. En el presente trabajo se realiza una revisión de la evidencia científica existente para determinar si la triple terapia es eficaz y segura, así como la asociación más favorable en el paciente con diabetes tipo 2. Revisando los estudios disponibles, se observa que la triple terapia mejora el control glucémico. Sin embargo, los ensayos clínicos aleatorizados disponibles en general no exceden el año de seguimiento, y no ofrecen datos sobre variables finales como morbilidad y mortalidad. En consecuencia, hasta el momento el beneficio a largo plazo y la seguridad de una triple terapia no están demostrados. En conclusión, con los datos disponibles actualmente no hay razón para retrasar la introducción de la insulina en el tratamiento de los pacientes con diabetes tipo 2 tras el fracaso de una terapia combinada doble, excepto en los casos de resistencia de los pacientes al inicio de la insulinización(AU)

Current guidelines differ in their recommendations for triple therapy when targets are not achieved with a combined treatment of two oral agents. In addition, they diverge also in the type of association and the name given for the triple therapy. In the present manuscript we review the available scientific evidence to determine whether triple therapy is effective and safe, as well as themore favorable association in patients with type 2 diabetes. Reviewing available literature, we have noticed that triple therapy improves glycemic control. However, available randomized control trials do not extend more than one year of follow-up and they don’t have data over endpoint variables as morbidity and mortality. Therefore, the long-term safety of triple therapy has not been demonstrated until now. In conclusion, with the currently available data there is no reason to delay introduction of insulin in the treatment of patients with type 2diabetes after failure of dual combination therapy, except in cases of patients’ resistance to initiate insulin therapy(AU)

Organising pneumonia - the experience of an outpatient clinic of a central hospital.

AIM: to characterise outpatients of a Portuguese central hospital diagnosed with organising pneumonia (OP) and compare results with current literature. METHODS: medical processes with diagnosis of OP were retrospectively studied as to demographics, aetiology, clinical and radiological features, average time until and date of diagnosis, laboratory and histological changes, treatment and relapse. Results - thirteen patients with a mean follow -up of 171.6 weeks (max 334 and min 28 weeks) were evaluated. Nine of these patients (70%) had cryptogenic OP (COP) while 30% had secondary OP (SOP), two with rheumatoid arthritis, one with dermatomyositis and another undergoing radiotherapy for breast cancer. Mean age was 55.6 (+ -15.3 years), 92% female, 77% were non -smokers. Average time until diagnosis was 77.2 weeks (min 3 and max 432 weeks). Symptoms at presentation were tiredness (92%), cough (85%), fever (65%), shortness of breath (54%), thoracic pain (23%) and weight loss (23%). At the time of diagnosis, the mean erythrocyte sedimentation rate was 70mm (max 170mm and min 16mm). C -reactive protein level was increased in eight patients. Significant leucocytosis was absent. Chest X -ray and chest CT scan showed bilateral distribution in 12 patients (92%). Consolidation with an air bronchogram was present in 12 patients and in four (31%), consolidation was migratory. Four patients (30%) underwent transbronchial pulmonary biopsy, all uncharacteristic and eight patients surgical pulmonary biopsy, four showed histological confirmation of SOP. Corticosteroids were started in 11 patients and average treatment was 61.6 weeks (16-288 weeks). 15% (2/13) had spontaneous resolution. Four patients (31%) relapsed, one of them five times. Two patients are dependent on a low dose of corticosteroids, one due to underlying disease and another due to multiple relapses. Therapy of relapse was corticosteroids alone in minimum effective dosage or associated to azathioprine or ciclosporin. DISCUSSION AND CONCLUSION: such a high incidence in females (92%) may be explained by the limited sample of patients. In 70% of the patients diagnosis were established by clinical and radiology criteria. Mean time to diagnosis was very variable which suggests that in some cases the disease was not diagnosed and treated as another interstitial lung disease or as recurrent pneumonia. Most patients (53.8%) had a favourable clinical course after treatment with corticosteroids with a very low number of relapses (30.8%), much lower than described by other authors (60%). Only in experienced centres should the diagnosis of OP established by clinical and radiological criteria.

[Epipericardial fat necrosis - Case report]. / Enfarte da gordura epipericárdica - A propósito de um caso clínico.

Epipericardial fat necrosis is an uncommon benign entity of unknown cause, with only 20 cases reported in the English-language literature. It should be remembered as a possible diagnosis in a person who presents with acute pleuritic chest pain and paracardiac density or pleural effusion on chest radiography (X-ray). The computed tomography (CT) or surgical approach allows the final diagnosis and characterization. The authors describe a case of a 48-year-old woman, admitted to our department because of complaints of fatigue, cough and sudden pleuritic pain on thoracic left side. The chest X-ray showed mild/moderate left pleural effusion and CT scan revealed local slight thickening of pericardium and epipericardial fat, surrounded by thick rim of higher density in the left cardiophrenic space. This made the diagnosis of epipericardial fat necrosis. During hospitalization the patient remained stable and was discharged home with symptomatic relieve therapy. Because of benign, self-limited nature of this entity, only conservative treatment is indicated.

Manifestaciones adrenérgicas de los tumores del tejido cromafín extraadrenal / High percentage of adrenergic symtoms in extraadrenal chromaffin toumors

ResumenEstudio descriptivo retrospectivo de 14 pacientes con un diagnóstico histológico de paraganglioma (PGL) recogidos en el Hospital Universitario de Vigo, Pontevedra, durante los últimos 25 años. Hemos analizado las características clínicas y la evolución de esta serie de enfermos.ResultadosLa forma de presentación de los 14 pacientes fue por efecto masa en 10, clínica adrenérgica en 3 e incidental en uno. Algunos enfermos con PGL simpáticos (PGLS) (6/9) y PGL parasimpáticos (PGLPS) (2/5) presentaron clínica de hiperproducción adrenérgica antes del diagnóstico. La determinación de catecolaminas urinarias fue positiva en los 4 enfermos con PGLPS en quienes se determinó. El tamaño tumoral medio fue de 37,8±18,9mm, sin diferencias entre los PGLS y los PGLPS. Dos PGLS fueron malignos. La evolución resultó favorable en 11 pacientes, 2 pacientes con PGLS fallecieron y el tumor de un paciente con PGLPS intracraneal no se pudo extirpar en su totalidad.ConclusionesLos PGL se presentan con frecuencia clínica adrenérgica secundaria a la producción de catecolaminas. Las características de estos tumores aconsejan un estudio detallado en un ámbito especializado antes de la cirugía(AU)

AbstractDescriptive retrospective study of 14 patients with paragangliomas (PGL) attended in the University Hospital of Vigo (Pontevedra) during the last 25 years to evaluating their characteristics and neuroendocrine potential.Results71.4% were diagnosed due to mass tumoral effect, 21.4% due to adrenergic symptoms and 7.1% incidentally. Regarding to symptoms and signs 66.7% of PGL Simpatic (PGLS) and 40% of PGL Parasimpatic (PGLPS) presented adrenergic symptoms. Urine catecholamine analysis was carried out to 4 PGLS and high levels were found in all patients. The tumoral size reached a mean value of 37.8±18.9mm, there were not differences found between both types of tumors. Inmunohistoquimia showed positive Chromogranine A stain in all patients. Two PGLS were maligns. Eleven patients had positive outcome, 2 PGLS died, and 1 PGLPS remains not cured.ConclusionsHigh percentage of patients had clinical manifestations related to catecholamine hyperproduction. We believe that due to the risk related to surgical treatment, malignance, multiple location and family associations, it would be advisable to carry out a complete examination prior to surgery(AU)

[High percentage of adrenergic symptoms in extraadrenal chromaffin tumors]. / Manifestaciones adrenérgicas de los tumores del tejido cromafín extraadrenal.

UNLABELLED: Descriptive retrospective study of 14 patients with paragangliomas (PGL) attended in the University Hospital of Vigo (Pontevedra) during the last 25 years to evaluating their characteristics and neuroendocrine potential. RESULTS: 71.4% were diagnosed due to mass tumoral effect, 21.4% due to adrenergic symptoms and 7.1% incidentally. Regarding to symptoms and signs 66.7% of PGL Simpatic (PGLS) and 40% of PGL Parasimpatic (PGLPS) presented adrenergic symptoms. Urine catecholamine analysis was carried out to 4 PGLS and high levels were found in all patients. The tumoral size reached a mean value of 37.8+/-18.9 mm, there were not differences found between both types of tumors. Inmunohistoquimia showed positive Chromogranine A stain in all patients. Two PGLS were maligns. Eleven patients had positive outcome, 2 PGLS died, and 1 PGLPS remains not cured. CONCLUSIONS: High percentage of patients had clinical manifestations related to catecholamine hyperproduction. We believe that due to the risk related to surgical treatment, malignance, multiple location and family associations, it would be advisable to carry out a complete examination prior to surgery.

Enfermedad de Behçet asociada a déficit de corticotropina / Behçet disease with isolated acth deficiency

Presentamos un paciente con enfermedad de Behçet de larga evolución, con predominio de manifestaciones neurológicas, que ingresó por insuficiencia suprarrenal, en el que se demostró déficit aislado de corticotropina (DAACTH). El DAACTH es una característica típica de las hipofisitis y se ha descrito en asociación con múltiples enfermedades autoinmunitarias; sin embargo, la afección hipotálamo-hipofisaria en la enfermedad de Behçet es excepcional. Revisamos los casos publicados y los posibles mecanismos patogénicos de esta asociación hasta ahora no descrita (AU)

We report a case of a patient with longstanding Behçet disease, with neurological symptoms predominantly, who became hospitalized for adrenal insufficiency, caused by isolated deficiency of corticotropin (DAACTH). DAACTH is a typical characteristic of hypophysitis, reported in association with many autoimmune diseases. Nevertheless, hypothalamic-pituitary injury in Behçet disease is exceptional. We review the literature and possible mechanisms of this association until now not reported (AU)

[Rate of undernutrition and response to specific nutritional therapy in Crohn's disease]. / Tasa de desnutrición y respuesta al tratamiento nutricional específico en la enfermedad de Crohn.

OBJECTIVES: to determine the rate of malnutrition in patients with Crohn's disease in our area (Substudy A). We assess in long-term the response of malnourished patients to treatment of nutritional supplement with TGF-beta2 (Substudy B). SUBJECTS: ninety-eight (51% females) patients with Crohn's disease without selection, ages: 39.2 +/- 15.19 years, range: 18-81 years were included in Substudy A. In Substudy B thirty-nine malnourished patients (52% females) were included with an average age of 36.41 +/- 5.2 years and range: 19-45 (Substudy B). METHODS: the design of the Substudy A was an observational and cross sectional study. Whereas, the Substudy B was a longitudinal, open intervention study with active (historical) control. The variables were anthropometric parameters, electrical bioimpedance, biochemical measures, index of disease activity, subjective global assessment and the kind of treatment that every patient has received. MAIN RESULTS: the malnutrition rate was 52%, being the most frequent the caloric malnutrition, followed by mixed malnutrition. Thirty four per cent of the patients had iron deficiency. Twelve months of nutritional therapy with supplement specifically enriched in TGF-beta2 improved the evolution of the disease determined by a decrease in CDAI. CONCLUSIONS: The rate of malnutrition was similar to that of previous studies realized in Spain. Our study confirms the high rate of iron deficiency that the patients suffer with Crohn's disease. The response to the treatment is favorable, especially regarding the natural history of the disease.

[Relapsing pleural effusion and gastric polyposis: a case report]. / Derrame pleural recidivante e polipose gástrica - Caso clínico.

The authors present the case of a lymphoproliferative disorder (LPD) with pleuro-pulmonary involvement. It was a very aggressive primary gastric lymphoma of the MALT subtype, diagnosed in an 86-year-old woman admitted in Pulmonology ward at our Hospital with pleural effusion. Helicobacter pylori search was negative, what is infrequent. The disease was already disseminated at the time of the diagnosis and did not respond to various treatment modalities, what is also an uncommon finding. Clinical presentation, diagnosis and management of this disease are reviewed, pointing out its unique features and comparing the particular aspects of this case with the published literature. The authors stress that LPD is an important diagnosis to be held in mind in the case of a pleural effusion of unknown aetiology.

Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease.

Large chromosomal regions can be suppressed in cancer cells as denoted by hypermethylation of neighbouring CpG islands and downregulation of most genes within the region. We have analysed the extent and prevalence of long-range epigenetic silencing at 2q14.2 (the first and best characterised example of coordinated epigenetic remodelling) and investigated its possible applicability as a non-invasive diagnostic marker of human colorectal cancer using different approaches and biological samples. Hypermethylation of at least one of the CpG islands analysed (EN1, SCTR, INHBB) occurred in most carcinomas (90%), with EN1 methylated in 73 and 40% of carcinomas and adenomas, respectively. Gene suppression was a common phenomenon in all the tumours analysed and affected both methylated and unmethylated genes. Detection of methylated EN1 using bisulfite treatment and melting curve (MC) analysis from stool DNA in patients and controls resulted in a predictive capacity of, 44% sensitivity in positive patients (27% of overall sensitivity) and 97% specificity. We conclude that epigenetic suppression along 2q14.2 is common to most colorectal cancers and the presence of a methylated EN1 CpG island in stool DNA might be used as biomarker of neoplastic disease.

Four years' follow up at a smoking cessation clinic.

UNLABELLED: Smoking is an important cause of pulmonary pathology and this addiction can be regarded as a chronic, recurrent disease. The benefits of smoking cessation are unquestionable and all physicians should become more active and assertive in recommending it. AIM: To characterise the population seeking medical support for smoking cessation and understand why some successfully stop smoking and others do not. MATERIAL AND METHODS: Retrospective analysis of medical records of outpatients in follow-up between January 2003 and June 2006. Age, gender, age at smoking initiation, smoking burden (number of pack-years), associated diseases, degree of dependence (Fagerström test for nicotine addiction), prior attempts at and motivation for smoking cessation, need for cognitive/behavioural support and success and abandonment rates were evaluated. RESULTS: Five hundred and twenty six patients were studied, 50% male with an average age of 45.5+/-11.4 years. Almost half (43.1 %; n=227) of the patients started smoking before the age of 15. Average smoking burden was 35.8+/-20 pack-years although 21.4% (n=113) smoked more than 50 pack-years. Respiratory disease was present in 52.1% (COPD, 39.9% and others, 12.2%) and cardiovascular disease in 14.6% of the patients. In 46% of patients (n=242) a relevant psychiatric disorder was identified; depression (21.4%), anxiety disorder (19.4%), other dependencies (2.1%) bipolar disorder (1.5%) and schizophrenia (0.6%). The evaluation of degree of addiction revealed maximum level in 69.7% of the patients (n=380). Many patients (72.2%; n=380) reported prior attempts to quit smoking. The strongest reasons for giving up smoking were concern over health (83.5%), financial issues (8.2%) and search for better quality of life (5.7%). Most patients (81.7%; n=430) had undergone nicotine replacement therapy; skin patches (53.3%), chewing gum (1.1%) or both (45.6%). Psychopharmacological treatment included administration of sedative-hypnotics (86.5%), bupropion hydrochloride (2.3%) and antidepressants (0.6%). Seventy six patients (14%) benefited from cognitive/ behavioural support. Two hundred and twenty three patients (42.4%) were successful in giving up smoking while 219 (41.6%) abandoned follow up, the majority after the first appointment. Most patients that abandoned follow up reported lack of motivation and the price of therapy. CONCLUSIONS: The population under study had a high rate of psychiatric disorders and a high level of dependence and lack of motivation that might justify the drop-out rate. Successful treatment was associated with close follow up, behavioural support and pharmacological therapy.

[Whole lung lavage - Report of four cases of alveolar proteinosis]. / Lavagem pulmonar total - A propósito de quatro casos de proteinose alveolar.

Whole lung lavage is a technique that was developed in the 1960s with the purpose of removing lipoproteinaceous material that accumulates in the bronchi of patients with alveolar proteinosis, leading to clinical and functional improvement. There has been an evolution in the technique; initially it was performed under local anesthesia to each segment of the lung and currently it is performed under general anesthesia sequentially to both lungs. This review describes the whole lung lavage, its major indication, alveolar proteinosis and some data on the experience of our hospital.

[High frequency of non-specific eating disorders in obese persons]. / Alta frecuencia de trastornos de la conducta alimentaria inespecíficos en personas obesas.

OBJECTIVES: Determine frequency of Eating Disorders and Non-Specific Eating Disorders and pathological behaviour in obese patients. SUBJECTS AND METHODS: The study includes fifty-four obese patients (BMI > or = 30) consecutively attended at the Nutrition Section of the University Hospital of Vigo. Aged 37.5 +/- 11.1. Range 18-58, 45 female and 9 male. CONTROL GROUP: 15 adult normal-weight subjects (11 female, 4 male), aged 35,3 +/- 9,2 años. Frequency of Eating Disorders was determined by a lifestyle clinical interview and the following questionnaires: Eating Attitudes Test 26 (EAT26), Bulimic Investigatory Test Edimburgh (BITE) and Questionnaire Eating Weight Patterns Revised (QEWP-R). RESULTS: Twelve out of 54 (20.6%) patients showed Pathological Behavior, while 5 (4.1%) and 3 (2.5%) had Non- Specific Eating Disorders and Classic Eating Disorders respectively, whereas in the control group non subjects showed psychological anomalies. When we divided obese patients by the degree of obesity, differences in the frequencies of the Eating Disorders was no observed. CONCLUSIONS: In our obese patients, Pathological Behavior was the most frequent finding followed for Non-Specific Eating Disorders and Classic Eating Disorders.