Statin use and survival in resectable pancreatic cancer: confounders and mechanisms.

A first point regards the possible activity of drugs other than statins, such as aspirin or metformin, against pancreatic cancer. As many patients use a combination of these drugs, one might speculate that the association between simvastatin and overall survival in resected pancreatic cancer patients might also be explained by the concomitant use of aspirin or metformin, or that these drugs might result synergistic, as hypothesized for colorectal cancer (3). We wonder whether the authors had access to data on aspirin or metformin use for their population. A second point regards the very high 45% rate of simvastatin or lovastatin users reported by the authors. This figure is different from that of many European countries, thus possibly limiting the attributable fraction of cases for whom the observed findings can be replicated

The use of complementary and alternative medicine is frequent in patients with pancreatic disorder

BACKGROUND: Herbal remedies and other complementary and alternative medicine (CAM) are used by 30% of the patients with liver and inflammatory bowel diseases. However, there are no data regarding CAM use in patients with pancreatic disorders, including potential pancreatotoxicity. AIM OF THE STUDY: The aim of the study was to assess the prevalence of CAM use in patients with pancreatic disorders and screen for pancreatotoxicity. MATERIALS AND METHODS: This was a cross-sectional survey of consecutive outpatients seen at a Pancreas Center. Data were collected in a specific questionnaire. Descriptive statistics were used to analyze the prevalence and the patterns of CAM use. Characteristics associated with CAM use were analyzed by appropriate statistics. RESULTS: Of 108 patients (52% male; mean age, 65±13 years), 47 (43.5%) used CAM. The use of CAM was more frequent among patients with previous acute pancreatitis (47%). Reported reasons for the use of CAM were to help standard therapies and for an overall better feeling. About 61% of the patients reported advantages with treatment. As compared with nonusers, CAM users were more often female (55% vs. 42%), with a higher school degree (43% vs. 36%), more frequently performing physical activity (51% vs. 41%), and reporting anxiety (45% vs. 31%). However, none of these differences were statistically significant. Three patients with previous acute pancreatitis reported the use of Serenoa repens that is potentially pancreatotoxic. DISCUSSION: The rate of CAM use in patients with pancreatic disorders is similar to those reported for other digestive diseases. CAM use seems to be more frequent in women with a higher education level and a "healthier lifestyle." Patients might not be aware of the potential pancreatotoxicity of CAM, which should be carefully considered by physician

Modulation of PKM alternative splicing by PTBP1 promotes gemcitabine resistance in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first-line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing (AS) of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence-free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favor the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, upregulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to upregulation of PTBP1 and modulation of PKM AS in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.Oncogene advance online publication, 3 August 2015; doi:10.1038/onc.2015.270

Rascacielos a la italiana. Construcción de gran altura en los años cincuenta y sesenta

In the fifties and sixties, while Italian engineering was receiving important international awards, the theme of the tall building attracted the attention of the best architects. They made it a field of design experimentation, immediately sensing how the strategic use of the structure could revolutionize the already stereotyped image of the all-steel and glass towers proposed by the International Style. Gio Ponti, Luigi Moretti and the BBPR thus created formidable partnerships with Pier Luigi Nervi and Arturo Danusso, the most active engineers in the field of skyscraper design. The result was at least three masterpieces, among the works created in those years: the Velasca tower and the Pirelli skyscraper in Milan and the Stock Exchange tower in Montreal, which, at the time of its completion, also marked the record for the highest reinforced concrete building in the world.En los años cincuenta y sesenta del siglo XX, mientras la ingeniería italiana recibía importantes premios internacionales, el diseño de los edificios en altura atraía la atención de los mejores arquitectos. Estos entendieron inmediatamente lo mucho que el empleo estratégico de la estructura habría podido revolucionar la ya de por sí estereotipada imagen de la torre de acero y vidrio propuesta por el Estilo Internacional, y lo convirtieron en un campo de experimentación. De esta forma Gio Ponti, Luigi Moretti y la BBPR desarrollaron extraordinarias colaboraciones con Pier Luigi Nervi y Arturo Danusso, los ingenieros más activos en el campo del diseño de rascacielos. De entre los proyectos realizados en esos años, este proceso de colaboración dió como resultado a al menos tres obras maestras: la torre Velasca, el rascacielos Pirelli y la torre de la Bolsa de Valores de Montreal. Esta última, en el momento de su finalización, además significó el récord del edificio de hormigón armado más alto del mundo

Epidemiology, clinical features and treatment of chronic pancreatitis. current knowledge and future perspectives [Epidemiologia, clinica e terapia medica della pancreatite cronica: evidenze attuali e sviluppi per il futuro]

La pancreatite cronica è una patologia dal complesso inquadramento sia dal punto di vista epidemiologico, con dati incerti sull’esatta prevalenza, sia dell’eziologia, a volte non individuabile e per la quale si sta delineando sempre più la rilevanza delle forme post-pancreatite acuta, con il fumo come fattore di rischio spesso sottovalutato rispetto all’alcol. La pancreatite cronica si associa ad aumento della mortalità e morbilità, legate soprattutto a patologie extrapancreatiche. L’eventuale presenza di insufficienza esocrina o endocrina pancreatica può essere, inoltre, alla base di complicanze anche gravi e spesso non prevenute per tempo. I deficit vitaminici e di micro- e macronutrienti vanno attentamente ricercati e corretti; questo sarà inoltre fondamentale per evitare complicanze quali l’osteoporosi. Il dolore è il sintomo più rilevante, ha una patogenesi complessa, legata non solo a fattori ostruttivi e meccanici o alla flogosi, ma anche un’alterazione cronica del processo di adattamento al dolore a livello del sistema nervoso centrale. Anche per questo la terapia del dolore è spesso inefficace. La chirurgia derivativa è indicata nelle forme con ostruzione duttale con risultati che sembrano superiori a quelli dell’endoscopia, e quella resettiva in quelle associate a massa infiammatoria. Una nuova frontiera è rappresentata poi dalla pancreasectomia totale con trapianto di insule, che offre ottimi risultati in termini di controllo del dolore con possibilità di evitare il diabete in una buona percentuale di pazienti. Questa rassegna discute tali “hot topics” racchiudendo sia le evidenze più recenti sull’argomento sia una riflessione su come evolveranno le nostre conoscenze su tale patologia.Chronic pancreatitis is a complex disease both for the epidemiology, with uncertain data on the exact prevalence, but also for the etiology, often not identified and for whom, compared to the past, post acute pancreatitis forms are showing a high impact; also smoking is an etiological factor often underestimated compared to alcohol. Chronic pancreatitis is associated with high mortality and morbidity, mostly due to extrapancreatic diseases. The eventual occurrence of exocrine or endocrine pancreatic insufficiency can lead to complications, often serious and not prevented in time. It is, in fact, well known how this can cause micro or macronutrient and vitamin deficit which, if not screened and corrected, can cause complications such as osteoporosis. Abdominal pain is the most relevant symptom, with a complex pathogenesis, due not only to obstructive or mechanical factors or inflammation, but also to a chronic alteration of the adaptation process of pain in the central nervous system. Also for this reason, therapies are often not effective. Derivative surgery is indicated in obstructive forms, with results superior to those of endoscopy, while resective surgery is indicated when an inflammatory mass is present. A new opportunity is total pancreatectomy with islet autotransplantation, which offers excellent results in terms of pain relief and possibility to avoid diabetes in a high percentage of patients. This review will discuss these hot topics comprehending both most recent evidence and a view on how our knowledge on this disease will change in the upcoming years

Common features between neoplastic and preneoplastic lesions of the biliary tract and the pancreas

The bile duct system and pancreas show many similarities due to their anatomical proximity and common embryological origin. Consequently, preneoplastic and neoplastic lesions of the bile duct and pancreas share analogies in terms of molecular, histological and pathophysiological features. Intraepithelial neoplasms are reported in biliary tract, as biliary intraepithelial neoplasm (BilIN), and in pancreas, as pancreatic intraepithelial neoplasm (PanIN). Both can evolve to invasive carcinomas, respectively cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary neoplasms arise in biliary tract and pancreas. Intraductal papillary neoplasm of the biliary tract (IPNB) share common histologic and phenotypic features such as pancreatobiliary, gastric, intestinal and oncocytic types, and biological behavior with the pancreatic counterpart, the intraductal papillary mucinous neoplasm of the pancreas (IPMN). All these neoplastic lesions exhibit similar immunohistochemical phenotypes, suggesting a common carcinogenic process. Indeed, CCA and PDAC display similar clinic-pathological features as growth pattern, poor response to conventional chemotherapy and radiotherapy and, as a consequence, an unfavorable prognosis. The objective of this review is to discuss similarities and differences between the neoplastic lesions of the pancreas and biliary tract with potential implications on a common origin from similar stem/progenitor cells

The mediterranean diet slows down the progression of aging and helps to prevent the onset of frailty: A narrative review

The aging population is rapidly increasing all over the world. This results in significant implications for the planning and provision of health and social care. Aging is physiologically characterized by a decrease in lean mass, bone mineral density and, to a lesser extent, fat mass. The onset of sarcopenia leads to weakness and a further decrease in physical activity. An insufficient protein intake, which we often observe in patients of advanced age, certainly accelerates the progression of sarcopenia. In addition, many other factors (e.g., insulin resistance, impaired protein digestion and absorption of amino acids) reduce the stimulation of muscle protein synthesis in the elderly, even if the protein intake is adequate. Inadequate intake of foods can also cause micronutrient deficiencies that contribute to the development of frailty. We know that a healthy eating style in middle age predisposes to so-called “healthy and successful” aging, which is the condition of the absence of serious chronic diseases or of an important decline in cognitive or physical functions, or mental health. The Mediterranean diet is recognized to be a “healthy food” dietary pattern; high adherence to this dietary pattern is associated with a lower incidence of chronic diseases and lower physical impairment in old age. The aim of our review was to analyze observational studies (cohort and case–control studies) that investigated the effects of following a healthy diet, and especially the effect of adherence to a Mediterranean diet (MD), on the progression of aging and on onset of frailty

Investigation of a passive control system for limiting cavitation inside turbomachinery under different operating conditions

Abstract Herein, a new passive control system for limiting cavitation inside turbomachinery has been applied to a NACA0009 hydrofoil. The basic idea is to introduce slots nearby its leading edge, connecting pressure and suction sides of the hydrofoil, in order to increase locally the pressure on its suction side and to prevent cavitation from developing. The cavitating flow developed around a two-dimensional hydrofoil is here considered since it is an archetype of cavitation nearby the leading edges of the impeller vanes. Thus, the flow field developed at the leading edge of both the original and modified hydrofoil has been studied at different angles of attack in order to reproduce a wide range of operating conditions that occur inside turbomachinery. Eventually, a comparison of their performance in terms of polars (C L and C D ) and vapour volume fractions (α v ) is performed