Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 312
Filtrar
Más filtros

Colección Oncologia Uruguay
Intervalo de año de publicación
1.
Dis Esophagus ; 35(11)2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-35641160

RESUMEN

The present study aims to compare the effectiveness of surgical and medical therapy in reducing the risk of cancer in Barrett's esophagus in a long-term evaluation. A prospective cohort was designed that compared Barrett's esophagus patients submitted to medical treatment with omeprazole or laparoscopic Nissen fundoplication. The groups were compared using propensity score matching paired by Barrett's esophagus length. A total of 398 patients met inclusion criteria. There were 207 patients in the omeprazole group (Group A) and 191 in the total fundoplication group (Group B). After applying the propensity score matching paired by Barrett's esophagus length, the groups were 180 (Group A) and 190 (Group B). Median follow-up was 80 months. Group B was significantly superior for controlling GERD symptoms. Group B was more efficient than Group A in promoting Barrett's esophagus regression or blocking its progression. Group B was more efficient than Group A in preventing the development of dysplasia and cancer. Logistic regression was performed for the outcomes of adenocarcinoma and dysplasia. Age and body mass index were used as covariates in the logistic regression models. Even after regression analysis, Group B was still superior to Group A to prevent esophageal adenocarcinoma or dysplasia transformation (odds ratio [OR]: 0.51; 95% confidence interval [CI]: 0.27-0.97, for adenocarcinoma or any dysplasia; and OR: 0.26; 95% CI: 0.08-0.81, for adenocarcinoma or high-grade dysplasia). Surgical treatment is superior to medical management, allowing for better symptom control, less need for reflux medication use, higher regression rate of the columnar epithelium and intestinal metaplasia, and lower risk for progression to dysplasia and cancer.


Asunto(s)
Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Laparoscopía , Humanos , Esófago de Barrett/complicaciones , Esófago de Barrett/tratamiento farmacológico , Esófago de Barrett/cirugía , Fundoplicación , Estudios Prospectivos , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/prevención & control , Neoplasias Esofágicas/diagnóstico , Adenocarcinoma/etiología , Adenocarcinoma/prevención & control , Adenocarcinoma/cirugía , Omeprazol
2.
Rev Med Liege ; 77(7-8): 462-467, 2022 Jul.
Artículo en Francés | MEDLINE | ID: mdl-35924504

RESUMEN

Dermatomyositis is an autoimmune disease mainly characterized by muscle and skin involvement. Its association with cancer is known but the term «paraneoplastic¼ remains debated. We report here the case of a 71-year-old woman with a new diagnosis of dermatomyositis with, at the same time, the discovery of a lung adenocarcinoma. Lung cancer was treated with pembrolizumab, an immune checkpoint inhibitor directed against the "Programmed cell Death protein 1" (PD-1) receptor. Three weeks later, the patient presented a severe flare of dermatomyositis. Administration of intravenous corticosteroids and infliximab were ineffective. Intravenous immunoglobulins were then administered, followed by subcutaneous methotrexate, with a progressive positive evolution. Flares of pre-existing autoimmune diseases are observed under immune check point inhibitors, even when the evolution of the cancer is favourable. These immune-related adverse events are often «mild to moderate¼ and severe immune related side effects are not more frequent when the patient has a pre-existing autoimmune disease. Treatment can be maintained in the majority of cases. However, as demonstrated in this clinical case, although immune checkpoint inhibitors are not contraindicated in autoimmune diseases, the presence of myositis requires special attention given the potential severity of flares.


: La dermatomyosite est une maladie auto-immune principalement caractérisée par une atteinte musculaire et cutanée. Son association avec le cancer est connue, mais le terme «paranéoplasique¼ reste débattu. Nous rapportons ici le cas d'une patiente de 71 ans avec un nouveau diagnostic de dermatomyosite et, au même moment, la découverte d'un adénocarcinome pulmonaire. La néoplasie pulmonaire a été traitée par pembrolizumab, un inhibiteur des points de contrôle immunitaire dirigé contre le récepteur «Programmed cell Death protein 1¼ (PD-1). Trois semaines plus tard, la patiente présentera une poussée sévère de dermatomyosite, ne répondant pas à la corticothérapie intraveineuse ni à l'infliximab. Des immunoglobulines intraveineuses sont alors administrées, suivies de méthotrexate sous-cutané, avec une évolution progressivement positive. On observe des poussées de maladies auto-immunes préexistantes sous inhibiteurs de points de contrôle immunitaire, même quand l'évolution néoplasique est favorable. Ces effets secondaires immuno-induits sont souvent «légers à modérés¼ et on n'observe pas plus de manifestations indésirables «sévères¼ lorsque le patient présente une maladie auto-immune pré-existante. Le traitement peut être maintenu dans la majorité des cas. Toutefois, comme démontré dans ce cas clinique, bien que les inhibiteurs de points de contrôle immunitaire ne soient pas contre-indiqués en cas de maladie auto-immune, la présence d'une myosite nécessite une attention particulière vu la gravité potentielle des poussées.


Asunto(s)
Adenocarcinoma del Pulmón , Antineoplásicos Inmunológicos , Enfermedades Autoinmunes , Dermatomiositis , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/inducido químicamente , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/tratamiento farmacológico , Anciano , Antineoplásicos Inmunológicos/efectos adversos , Enfermedades Autoinmunes/complicaciones , Dermatomiositis/complicaciones , Dermatomiositis/diagnóstico , Dermatomiositis/tratamiento farmacológico , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico
3.
Eur J Neurol ; 28(1): 7-14, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33058321

RESUMEN

BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.


Asunto(s)
COVID-19 , Enfermedades del Sistema Nervioso/terapia , Pandemias , Manejo de Atención al Paciente , Consenso , Técnica Delphi , Guías como Asunto , Humanos , Neurología
4.
Tech Coloproctol ; 25(11): 1199-1207, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34224035

RESUMEN

BACKGROUND: The EndoLuminal Surgical System (ELS) is an emerging non-linear robotic system specifically designed for transanal surgery that allows for excision of colorectal neoplasia and luminal defect closure. METHODS: An evaluation of ELS was conducted by a single surgeon in a preclinical setting at the EndoSurgical Center of Florida in Orlando, between October 1st, 2020 and December 31st, 2020, using porcine colon as a model. Mock lesions measured 2.5 to 3.5 cm were excised partial-thickness. Specimen quality and excision time was assessed and evaluated. RESULTS: Twenty consecutive robotic transanal minimally invasive surgery (TAMIS) operations utilizing the ELS system were successfully performed without fragmentation. The mean and standard deviation procedure time for all 20 cases was 18.41 ± 14.15 min. The latter 10 cases were completed in substantially less time, suggesting that ELS requires at least 10 preclinical cases for a surgeon to become familiar with the technology. A second task, namely suture closure of the partial-thickness defect, was performed in 9 of the 20 cases. Mean time and standard deviation for this task measured 27.89 ± 10.07 min. There were no adverse events. CONCLUSIONS: ELS was successful in performing the tasks of partial-thickness disc excision and closure in a preclinical evaluation. Further study is necessary to determine its clinical applicability.


Asunto(s)
Cirugía Colorrectal , Neoplasias del Recto , Procedimientos Quirúrgicos Robotizados , Cirugía Endoscópica Transanal , Humanos , Recto
5.
Rev Med Liege ; 76(5-6): 419-424, 2021 May.
Artículo en Francés | MEDLINE | ID: mdl-34080374

RESUMEN

Glioblastoma is the most common primary malignant brain tumor. Despite treatments combining excisional surgery, chemotherapy, and radiotherapy, overall survival remains low and the incidence of tumor recurrence remains high. Advances in the understanding of the disease, particularly its molecular biology and the mechanisms of action of systemic and radiotherapeutic treatments, as well as the development of image-guided surgical techniques, offer hope for the control of this hitherto incurable disease.


Le glioblastome est la tumeur cérébrale maligne primitive la plus fréquente. Malgré des traitements combinant la chirurgie d'exérèse, la chimiothérapie et la radiothérapie, la survie globale reste faible avec une incidence élevée de récidive tumorale. Les progrès dans la compréhension de la maladie, et en particulier de la biologie moléculaire et des mécanismes d'action des traitements systémiques et radiothérapeutiques, de même que le développement des techniques chirurgicales guidées par l'image, permettent d'entrevoir un espoir dans le contrôle de cette maladie jusqu'ici incurable.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Biomarcadores de Tumor , Neoplasias Encefálicas/terapia , Metilación de ADN , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Mutación , Recurrencia Local de Neoplasia/genética , Pronóstico
6.
Proc Biol Sci ; 287(1922): 20192862, 2020 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-32156209

RESUMEN

Characterizing functional trait variation and covariation, and its drivers, is critical to understand the response of species to changing environmental conditions. Evolutionary and environmental factors determine how traits vary among and within species at multiple scales. However, disentangling their relative contribution is challenging and a comprehensive trait-environment framework addressing such questions is missing in lichens. We investigated the variation in nine traits related to photosynthetic performance, water use and nutrient acquisition applying phylogenetic comparative analyses in lichen epiphytic communities on beech across Europe. These poikilohydric organisms offer a valuable model owing to their inherent limitations to buffer contrasting environmental conditions. Photobiont type and growth form captured differences in certain physiological traits whose variation was largely determined by evolutionary processes (i.e. phylogenetic history), although the intraspecific component was non-negligible. Seasonal temperature fluctuations also had an impact on trait variation, while nitrogen content depended on photobiont type rather than nitrogen deposition. The inconsistency of trait covariation among and within species prevented establishing major resource use strategies in lichens. However, we did identify a general pattern related to the water-use strategy. Thus, to robustly unveil lichen responses under different climatic scenarios, it is necessary to incorporate both among and within-species trait variation and covariation.


Asunto(s)
Líquenes , Fenotipo , Biodiversidad , Cambio Climático , Europa (Continente) , Nitrógeno , Fotosíntesis , Filogenia
7.
World J Urol ; 38(9): 2115-2122, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31289843

RESUMEN

PURPOSE: This paper explores the feasibility of a new therapy for the treatment of hypospadias patients. Hypospadias is a very common congenital malformation of male genitals, with very high rate of recurrences after surgery. The field of regenerative medicine, which offers innovative solutions for many pathologies, still does not offer reliable solution for this pathology. Here, we propose quality, safety, and clinical feasibility assessment for an oral mucosa advanced therapy medicinal product (ATMP) grown on a biocompatible scaffold for a clinical study on urethral reconstruction of hypospadias patients. METHODS: Urethral and oral mucosal epithelia from donor biopsies were cultivated between two fibrin layers, under clinical-grade conditions for cell and tissue characterization and comparison, aimed at tissue engineering. In addition, single-clone analyses were performed to analyze gene expression profiles of the two epithelia by microarray technology. RESULTS: Oral mucosa appeared suitable for urethral reconstruction. The resulting ATMP was proven to maintain stem cells and regenerative potency. The preclinical safety studies were performed on human tissues to assess abnormalities and tumorigenicity, and confirmed the safety of the ATMP. Finally, the patient selection and the clinical protocol for the upcoming clinical trial were defined. CONCLUSIONS: Against this backdrop, in this paper, we are proposing a new reproducible and reliable ATMP for the treatment of hypospadias.


Asunto(s)
Hipospadias/cirugía , Mucosa Bucal/trasplante , Uretra/cirugía , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Humanos , Técnicas In Vitro , Masculino , Porcinos , Ingeniería de Tejidos , Andamios del Tejido , Procedimientos Quirúrgicos Urológicos Masculinos/métodos
8.
Eur J Neurol ; 27(9): 1727-1737, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32558002

RESUMEN

BACKGROUND AND PURPOSE: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. METHODS: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. RESULTS: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. CONCLUSION: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.


Asunto(s)
Anosmia/etiología , COVID-19/complicaciones , Cefalea/etiología , Mialgia/etiología , Agitación Psicomotora/etiología , Europa (Continente) , Encuestas Epidemiológicas , Humanos , Neurología
9.
Eur J Neurol ; 27(1): 136-143, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31325350

RESUMEN

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.


Asunto(s)
Conducta Alimentaria , Estilo de Vida , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/epidemiología , Adulto , Niño , Bases de Datos Factuales , Femenino , Humanos , Infecciones/complicaciones , Italia/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo
10.
Soft Matter ; 16(44): 10122-10131, 2020 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-32780784

RESUMEN

The aggregation properties of semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for the treatment of type 2 diabetes, have been investigated by spectroscopic techniques (UV-Vis absorption, steady-state and time-resolved fluorescence, and electronic circular dichroism) and molecular dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 µM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by blue luminescence and a ß-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs.


Asunto(s)
Diabetes Mellitus Tipo 2 , Simulación de Dinámica Molecular , Péptidos Similares al Glucagón , Humanos , Péptidos
11.
Support Care Cancer ; 28(12): 5973-5982, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32285261

RESUMEN

PURPOSE: This study aims to explore the relation between the dimension of fear of cancer recurrence (FCR) in haematological cancer patients relapse-free for at least 2 years and socio-demographic, related to the disease, psychological and existential factors. METHODS: A sample of 75 haematological cancer patients agreed to participate in the study through a self-reported online questionnaire (51.9% males). A total of 70.1% had a low recurrence risk. The questionnaire included socio-demographic (gender, age, civil status, level of education and number of children), related to the disease (diagnosis, therapeutic line and years since diagnosis), psychological (anxiety and depression), existential (purpose in life; PIL) factors and Fear of Cancer Recurrence Concerns Inventory (FCRI). Simple and multiple linear regressions were conducted for the analyses, and we performed some preliminary analysis on the reliability of the FCRI. FINDINGS: A total of 53.3% of participants showed clinical levels of FCR on the severity dimension, which was higher than found in previous research in other cancer patients. The coping strategies, triggers, severity and psychological distress dimensions showed higher mean values. Women, patients with indolent non-Hodgkin lymphomas, years since diagnosis, anxiety and purpose in life are significantly related to one or more dimensions of FCRI. IMPLICATIONS: It is important that the clinicians have at their disposal multiple possibilities to help patients cope with haematological cancer. If future research will confirm the results of this study, the negative correlation between FCR and PIL can suggest indications for planning interventions based on a salutogenic approach.


Asunto(s)
Ansiedad/psicología , Existencialismo/psicología , Miedo/psicología , Neoplasias Hematológicas/psicología , Recurrencia Local de Neoplasia/psicología , Adaptación Psicológica , Adulto , Trastornos de Ansiedad/psicología , Femenino , Neoplasias Hematológicas/terapia , Humanos , Masculino , Persona de Mediana Edad , Trastornos Fóbicos/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Adulto Joven
12.
Rev Med Liege ; 75(3): 190-198, 2020 Mar.
Artículo en Francés | MEDLINE | ID: mdl-32157846

RESUMEN

We discuss the diagnostic workup of a 62 year old woman without any significant past medical history. We take this opportunity to point out three aspects : 1. The necessary contextualization of the whole process allowing to avoid unrealistic differentials; 2. The requirement to prioritize the diagnostic tests as a function of their expected contribution to the diagnosis, their invasive characteristic and their availability, including their cost and 3. The evolving character of the diagnostic process that, if needed, has to be reconsidered to integrate the information obtained from the first diagnostic tests and the evolution of the patient.


Nous discutons la démarche sémiologique et diagnostique d'un cas d'ataxie chez une patiente de 62 ans, indemne de tout antécédent médical significatif. A l'occasion de cette vignette diagnostique, nous insistons sur trois aspects : 1. La nécessité de contextualiser la démarche pour éviter d'évoquer des diagnostics différentiels irréalistes; 2. La nécessité de choisir les examens complémentaires pertinents en les hiérarchisant en fonction de la probabilité de contribuer au diagnostic, de leur invasivité et de leur disponibilité, y compris de leur coût et 3. Le caractère évolutif de la démarche diagnostique qu'il faut pouvoir remettre en question au fil des informations que fournissent l'évolution du patient et les résultats des investigations.


Asunto(s)
Accidentes por Caídas , Ataxia , Ataxia/diagnóstico , Ataxia/etiología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad
13.
Dis Esophagus ; 30(10): 1-8, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28859394

RESUMEN

Achalasia of the cardia is associated with an increased risk of esophageal carcinoma. The real burden of achalasia at the malignancy genesis is still a controversial issue. Therefore, there are no generally accepted recommendations on follow-up evaluation for achalasia patients. This study aims to estimate the risk of esophageal adenocarcinoma and squamous cell carcinoma in achalasia patients. We searched for association between carcinoma and esophageal achalasia in databases up to January 2017 to perform a systematic review and meta-analysis. A total of 1,046 studies were identified from search strategy, of which 40 were selected for meta-analysis. A cumulative number of 11,978 esophageal achalasia patients were evaluated. The incidence of squamous cell carcinoma was 312.4 (StDev 429.16) cases per 100,000 patient-years at risk. The incidence of adenocarcinoma was 21.23 (StDev 31.6) cases per 100,000 patient-years at risk. The prevalence for esophageal carcinoma was 28 carcinoma cases in 1,000 esophageal achalasia patients (CI 95% 2, 39). The prevalence for squamous cell carcinoma was 26 cases in 1,000 achalasia patients (CI 95% 18, 39) and for adenocarcinoma was 4 cases in 1,000 achalasia patients (CI 95% 3, 6).The absolute risk increase for squamous cell carcinoma was 308.1 and for adenocarcinoma was 18.03 cases per 100,000 patients per year. To the best of our knowledge, this is the first meta-analysis estimating the burden of achalasia as an esophageal cancer risk factor. The high increased risk rate for cancer in achalasia patients points to a strict endoscopic surveillance for these patients. Also, the increased risk for developing adenocarcinoma in achalasia patients suggests fundoplication after myotomy, to avoid esophageal reflux and Barret esophagus, a known risk factor for adenocarcinoma.


Asunto(s)
Adenocarcinoma/epidemiología , Carcinoma de Células Escamosas/epidemiología , Acalasia del Esófago/epidemiología , Neoplasias Esofágicas/epidemiología , Humanos , Incidencia , Prevalencia , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia
14.
Br J Dermatol ; 175(5): 1030-1037, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27473757

RESUMEN

BACKGROUND: Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease. OBJECTIVES: To obtain information about genetic predisposition to CM in Ticino, the southern region of Switzerland, a zone with moderate-to-high CM incidence. METHODS: We identified germline mutations in highly CM-associated genes (CDKN2A and CDK4) and low/medium-penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first- or second-degree relatives. Healthy blood donors (n = 146) were included as a control group. RESULTS: From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty-six were melanoma-prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83-9·20). At least one MC1R melanoma-associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%). CONCLUSIONS: Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population.


Asunto(s)
Mutación de Línea Germinal/genética , Melanoma/genética , Proteínas de Neoplasias/genética , Neoplasias Cutáneas/genética , Adulto , Edad de Inicio , Quinasa 4 Dependiente de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Femenino , Efecto Fundador , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Melanoma/epidemiología , Factor de Transcripción Asociado a Microftalmía/genética , Persona de Mediana Edad , Linaje , Polimorfismo Genético/genética , Receptor de Melanocortina Tipo 1/genética , Neoplasias Cutáneas/epidemiología , Suiza/epidemiología
15.
Eur J Neurol ; 23(7): 1218-27, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27105632

RESUMEN

BACKGROUND AND PURPOSE: Seizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long-term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance). METHODS: People with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined. RESULTS: In all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person-years. 428 (59%) were seizure-free. The probability of achieving 2-year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2- and 5-year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns. CONCLUSION: The long-term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well-defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enfermedad Crónica , Resistencia a Medicamentos , Femenino , Humanos , Lactante , Italia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Pronóstico , Recurrencia , Inducción de Remisión , Adulto Joven
17.
Br J Cancer ; 112(10): 1717-24, 2015 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-25897673

RESUMEN

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.


Asunto(s)
Androstenos/uso terapéutico , Variaciones en el Número de Copia de ADN , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Receptores Androgénicos/sangre , Esteroide 17-alfa-Hidroxilasa/sangre , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , ADN/genética , Supervivencia sin Enfermedad , Humanos , Calicreínas/sangre , Masculino , Persona de Mediana Edad , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/enzimología , Receptores Androgénicos/genética , Estudios Retrospectivos , Esteroide 17-alfa-Hidroxilasa/genética
18.
Neuropathol Appl Neurobiol ; 41(2): e29-40, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25041908

RESUMEN

AIMS: Human cytomegalovirus (HCMV) is a ubiquitous beta human herpesvirus able to influence infected cell survival and proliferation and to modulate the host immune response. As there is accumulating evidence that HCMV is detected in primary intracranial astrocytic tumours, in this study we looked for the presence of HCMV in intracranial tumours and tried to correlate this eventual presence with the anti-HCMV systemic immunoreactivity and with the detection of HCMV in peripheral blood. METHODS: In this study, we analysed 43 glioblastomas (GBM), 14 oligodendrogliomas (OL) and 20 meningiomas (MG) by immunofluorescence (IF) targeting HCMV immediate early antigen (IE1) and by nested PCR (nPCR) amplifying HCMV glycoprotein B (gB). RESULTS: Detection of IE1 by IF showed the presence of HCMV in 70% of GBM, 57% of OL and 85% of MG, in contrast to gB nPCR, which detected HCMV in only 50% of GBM, 38% of OL and 46% of MG. Unexpectedly, HCMV DNA and antigens were detected within GBM, OL and MG of patients that exhibit negative viral serology. More surprisingly, PCR on the peripheral blood did not detect HCMV in patients with a HCMV-positive tumour. CONCLUSIONS: Our results are in agreement with previous observations demonstrating HCMV in glial tumours and highlight the presence of HCMV in meningiomas. We also showed that anti-HCMV specific systemic immunoreactivity and detection of HCMV in peripheral blood are not predictive of HCMV presence in primary intracranial tumours.


Asunto(s)
Neoplasias Encefálicas/virología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/inmunología , ADN Viral/análisis , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Proteínas Inmediatas-Precoces/análisis , Mediciones Luminiscentes , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Seroepidemiológicos
19.
Acta Neurol Scand ; 132(4): 235-41, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25690532

RESUMEN

OBJECTIVES: Clinical predictors of falls in patients with Parkinson disease (PD) are fairly inaccurate. Stabilometric measures appear useful in investigating the relationship between balance, sensory disturbance, and falls. The aim of the study was to identify the best combination of clinical and stabilometric tests to predict falls prospectively. MATERIALS & METHODS: Fifty-three consecutive subjects with PD or parkinsonisms at risk of falls were included and followed for 6 months. Clinical variables were used as fall predictors: the Unified Parkinson Disease's Rating Scale (motor section) and the Longitudinal Aging study Amsterdam Physical Activity Questionnaire (LAPAQ). Variables from stabilometric platform underwent a principal component analysis. Multivariate logistic models were used to predict fallers using fall status (fallers: 1 + falls; recurrent fallers: 2 + falls) as dependent variable. RESULTS: Seven patients were lost to follow up, leaving 46 evaluable subjects. Of these, 32 (70%) were fallers and 22 (48%) were recurrent fallers. The only variable predicting fallers was the LAPAQ (odd ratio [OR] 0.99 (95% confidence interval [CI] 0.98-1.00); accuracy 71.7%; sensitivity 87.5%; specificity 35.7%). For recurrent fallers, Factor 2 (body sway velocity) (OR 2.37; 95% CI 1.01-5.58) and, in part, LAPAQ (OR 0.99; 95% CI 0.98-1.00) retained significance in the multivariate model, showing an accuracy of 76.9%, a sensitivity of 77.8%, and a specificity of 76.2%. CONCLUSIONS: A combination of clinical and instrumental tools is useful to identify fallers in PD or parkinsonisms. Body sway velocity and ability to perform the activities of daily living are the best predictors of recurrent falls.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Enfermedad de Parkinson/epidemiología , Accidentes por Caídas/prevención & control , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Equilibrio Postural , Factores de Riesgo
20.
Folia Morphol (Warsz) ; 74(1): 33-41, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25792393

RESUMEN

The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA