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1.
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2.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3.
  • Proletov, Ian, et al. (författare)
  • Primary and secondary glomerulonephritides 1.
  • 2014
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 29 Suppl 3:May, s. 186-200
  • Tidskriftsartikel (refereegranskat)
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4.
  • Scandale, Walter, et al. (författare)
  • Apparatus to study crystal channeling and volume reflection phenomena at the SPS H8 beamline
  • 2008
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 79:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A high performance apparatus has been designed and built by the H8-RD22 collaboration for the study of channeling and volume reflection phenomena in the interaction of 400 GeVc protons with bent silicon crystals, during the 2006 data taking in the external beamline H8 of the CERN SPS. High-quality silicon short crystals were bent by either anticlastic or quasimosaic effects. Alignment with the highly parallel (8 μrad divergence) proton beam was guaranteed through a submicroradian goniometric system equipped with both rotational and translational stages. Particle tracking was possible by a series of silicon microstrip detectors with high-resolution and a parallel plate gas chamber, triggered by various scintillating detectors located along the beamline. Experimental observation of volume reflection with 400 GeVc protons proved true with a deflection angle of (10.4±0.5) μrad with respect to the unperturbed beam, with a silicon crystal whose (111) planes were parallel to the beam. © 2008 American Institute of Physics.
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5.
  • Scandale, Walter, et al. (författare)
  • Deflection of 400GeV/c proton beam with bent silicon crystals at the CERN Super Proton Synchrotron
  • 2008
  • Ingår i: Physical Review Special Topics - Accelerators and Beams. - 1098-4402. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents a detailed study of the deflection phenomena of a 400GeV/c proton beam impinging on a new generation of bent silicon crystals; the tests have been performed at the CERN Super Proton Synchrotron H8 beam line. Channeling and volume reflection angles are measured with an extremely precise goniometer and with high resolution silicon microstrip detectors. Volume reflection has been observed and measured for the first time at this energy, with a single-pass efficiency as large as 98%, in good agreement with the simulation results. This efficiency makes volume reflection a possible candidate for collimation with bent crystals at the CERN Large Hadron Collider. © 2008 The American Physical Society.
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6.
  • Scandale, Walter, et al. (författare)
  • Double volume reflection of a proton beam by a sequence of two bent crystals
  • 2008
  • Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 658:4, s. 109-111
  • Tidskriftsartikel (refereegranskat)abstract
    • The doubling of the angle of beam deflection due to volume reflection of protons by a sequence of two bent silicon crystals was experimentally observed at the 400 GeV proton beam of the CERN SPS. A similar sequence of short bent crystals can be used as an efficient primary collimator for the Large Hadron Collider.
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9.
  • Archibugi, Livia, et al. (författare)
  • Gynecological and reproductive factors and the risk of pancreatic cancer : A case-control study
  • 2020
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 20:6, s. 1149-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: /Objectives: Pancreatic ductal adenocarcinoma (PDAC) has a higher incidence in men compared to women, although the difference in known risk factors cannot explain this disparity completely. Reproductive and hormonal factors have been demonstrated in pre-clinical studies to influence pancreatic carcinogenesis, but the few published data on the topic are inconsistent. The aim was to investigate the role of reproductive and hormonal factors on PDAC occurrence in women.METHODS: We conducted a unicenter case-control study; PDAC cases were matched to controls by age with a 1:2 ratio. Risk factors were screened through questionnaires about gynecologic and medical history. Comparisons were made using Chi-square and Fisher's exact tests where appropriate for categorical variables and Student's t-test for continuous variables. Logistic regression was used to calculate Odds Ratios (ORs) and their 95% confidence intervals (CI). Multivariable logistic regression models were adjusted for potential confounders.RESULTS: 253 PDAC and 506 matched controls were enrolled. At logistic regression multivariable analysis adjusted for confounding factors, older age at menopause (OR:0.95 per year; 95% CI:0.91-0.98; p = 0.007), use of Oral Contraceptives (OR:0.52; 95% CI:0.30-0.89; p = 0.018), use of Hormonal Replacement Therapy (OR:0.31; 95% CI:0.15-0.64; p = 0.001), and having had two children (OR:0.57; 95% CI:0.38-0.84; p = 0.005) were significant, independent protective factors for the onset of PDAC.CONCLUSIONS: These data confirm some previous findings on menopause age and number of births while, to our knowledge, this is the first study to show a protective effect of HRT and OC use. The results collectively support the hypothesis that exposure to estrogens plays a protective role towards PDAC.
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10.
  • Baloch, Ramen Munir, et al. (författare)
  • Indoor air pollution, physical and comfort parameters related to schoolchildren's health : Data from the European SINPHONIE study
  • 2020
  • Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 739
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial knowledge is available on the association of the indoor school environment and its effect among schoolchildren. In the same context, the SINPHONIE (School indoor pollution and health: Observatory network in Europe) conducted a study to collect data and determine the distribution of several indoor air pollutants (IAPs), physical and thermal parameters and their association with eye, skin, upper-, lower respiratory and systemic disorder symptoms during the previous three months. Finally, data from 115 schools in 54 European cities from 23 countries were collected and included 5175 schoolchildren using a harmonized and standardized protocol. The association between exposures and the health outcomes were examined using logistic regression models on the environmental stressors assessed in classroom while adjusting for several confounding factors; a VOC (volatile organic compound) score defined as the sum of the number of pollutants to which the children were highly exposed (concentration > median of the distribution) in classroom was also introduced to evaluate the mul tiexposu re - outcome association. Schoolchildren while adjusting for several confounding factors. Schoolchildren exposed to above or equal median concentration of PM2.5, benzene, limonene, ozone and radon were at significantly higher odds of suffering from upper, lower airways, eye and systemic disorders. Increased odds were also observed for any symptom (sick school syndrome) among schoolchildren exposed to concentrations of limonene and ozone above median values. Furthermore, the risks for upper and lower airways and systemic disorders significantly increased with the VOCs score. Results also showed that increased ventilation rate was significantly associated with decreased odds of suffering from eye and skin disorders whereas similar association was observed between temperature and upper airways symptoms. The present study provides evidence that exposure to IAPs in schools is associated with various health problems in children. Further investigations are needed to confirm our findings. (C) 2020 Elsevier B.V. All rights reserved.
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11.
  • Cameli, Matteo, et al. (författare)
  • ACUTE HF score, a multiparametric prognostic tool for acute heart failure : A real-life study
  • 2019
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 296, s. 103-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Acute heart failure (AHF) is the first cause of hospitalization for over-65 individuals, associated with high mortality and readmission rate. The aim of this study was to assess the prognostic value of a multiparametric score combining clinical, biochemical and echocardiographic indexes in AHF for clinical practice.Methods: 830 patients hospitalized for AHF were enrolled. Exclusion criteria were: active neoplasms; previous heart transplantation or left ventricular assist device implantation. Different variables were analyzed: etiology of AHF, clinical and biochemical data, lung congestion on chest-X ray, echocardiographic parameters and administered therapy. The endpoints were: all-cause mortality at 30 days, 6 months and 5 years and the duration of hospitalization.Results: 771 patients met eligibility criteria. Using the univariate and multivariate analysis the indexes with the best correlation with outcome were discretized and used to create the ACUTE HF score, computed as: 1.4*[serum creatinine>2 mg/dl] + 0.8*[ejection fraction<30] + 0.7*[age > 76] + 0.7*[prior hospitalization for AHF] + 0.9*[prior stroke/transient ischemic attack] + 0.5*[more than moderate mitral regurgitation] + 0.8*[use of non-invasive ventilation] and used to divide patients into 3 groups according to the risk of 6-months mortality. With the receiver operating curves and Kaplan-Meier analysis, this score proved to have a high predictive power for mortality at 30 days, 6 months and 5 years from hospitalization, and for event-free survival rates, providing a risk stratification capability superior to that of single variables.Conclusions: The ACUTE HF score could be a complete and useful tool for assessing prognosis of AHF patients. It could represent a step in the long standardization pathway of prognostic protocols for AHF.
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12.
  • Cameli, Matteo, et al. (författare)
  • Safe performance of echocardiography during the COVID-19 pandemic : a practical guide
  • 2020
  • Ingår i: Reviews in Cardiovascular Medicine. - : IMR Press. - 1530-6550 .- 2153-8174. ; 21:2, s. 217-223
  • Forskningsöversikt (refereegranskat)abstract
    • Coronavirus disease-2019 (COVID-19) outbreak has become a worldwide healthcare emergency, with continuously growing number of infected subjects. Considering the easy virus spread through respiratory droplets produced with cough, sneezes or spit or through close contact with infected people or surfaces, healthcare workers are further exposed to COVID-19. Particularly, echocardiography remains an essential diagnostic service which, due to the close contact with patients during the exam, provides echocardiographers high-risk of contagion. Therefore, the common modalities of performing echocardiography should be improved in this scenario, avoiding performing unnecessary exams, using the appropriate personal protective equipment depending on patients' status and location, optimizing time-effectiveness of the echocardiographic study and accurately sanitizing the environment and devices after each exam. This paper aims to provide a simple guide for the clinicians to balance between providing the best care to each patient and protecting themselves and other patients from the spread of the virus. It also proposes the use of the mnemonic PREVENT to resume the crucial indications to be followed for the execution of appropriate echocardiographic examination during the COVID-19 pandemic.
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13.
  • Cárdenas-Jaén, Karina, et al. (författare)
  • Chronic use of statins and acetylsalicylic acid and incidence of post-endoscopic retrograde cholangiopancreatography acute pancreatitis : A multicenter, prospective, cohort study
  • 2021
  • Ingår i: Digestive Endoscopy. - : Wiley-Blackwell. - 0915-5635 .- 1443-1661. ; 33:4, s. 639-647
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Post-endoscopic retrograde cholangiopancreatography (ERCP) acute pancreatitis (PEP) is a frequent complication of this endoscopic procedure. Chronic statin intake has been linked to lower incidence and severity of acute pancreatitis (AP). Periprocedural rectal administration of non-steroidal anti-inflammatory drugs is protective against PEP, but the role of chronic acetylsalicylic acid (ASA) treatment is unclear. We aimed to investigate whether statins and chronic ASA intake are associated with lower risk of PEP.METHODS: An international, multicenter, prospective cohort study. Consecutive patients undergoing ERCP in seven European centers were included. Patients were followed-up to detect those with PEP. Multivariate analysis by means of binary logistic regression was performed, and adjusted odds ratios (aORs) were calculated.RESULTS: A total of 1150 patients were included, and 70 (6.1%) patients developed PEP. Among statins users, 8.1% developed PEP vs. 5.4% among non-users (P = 0.09). Multivariate analysis showed no association between statin use and PEP incidence (aOR 1.68 (95% CI 0.94-2.99, P = 0.08)). Statin use had no effect on severity of PEP, being mild in 92.0% of statin users vs. 82.2% in non-statin users (P = 0.31). Chronic ASA use was not associated with PEP either (aOR 1.02 (95% CI 0.49-2.13), P = 0.96). Abuse of alcohol and previous endoscopic biliary sphincterotomy were protective factors against PEP, while >1 pancreatic guidewire passage, normal bilirubin values, and duration of the procedure >20 minutes, were risk factors.CONCLUSIONS: The use of statins or ASA is not associated with a lower risk or a milder course of PEP.
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14.
  • Clark, Andrew G., et al. (författare)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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15.
  • Crippa, Stefano, et al. (författare)
  • A tug-of-war in intraductal papillary mucinous neoplasms management : Comparison between 2017 International and 2018 European guidelines
  • 2021
  • Ingår i: Digestive and Liver Disease. - : Elsevier. - 1590-8658 .- 1878-3562. ; 53:8, s. 998-1003
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: 2017 International and 2018 European guidelines are the most recent guidelines for intraductal papillary mucinous neoplasms management.AIM: to evaluate the diagnostic accuracy of these guidelines in identifying malignant IPMN.METHODS: data from resected patients with IPMN were collected in two referral centers. Features of risk associated to cancerous degeneration described in International and European guidelines were retrospectively applied. Sensitivity, specificity, positive and negative predictive value in detecting malignant disease were calculated.RESULTS: the study includes 627 resected patients. European guidelines suggest resection in any patient with at least one feature of moderate-risk. International guidelines suggest that patients with moderate-risk features undergo endoscopic ultrasound before surgery. European guidelines had a higher sensitivity (99.2% vs. 83%) but a lower positive predictive value (59.5% vs. 65.8%) and Specificity (2% vs. 37.5%). European guidelines detected almost all malignancies, but 40% of resected patients had low-grade dysplasia. 297 patients underwent endoscopic ultrasound before surgery. 31/116 (26.7%) tumors radiologically classified as "worrisome features" were reclassified as "high-risk stigmata" by endoscopic ultrasound and 24/31 were malignant IPMN.CONCLUSIONS: European and International guidelines have a relatively low diagnostic accuracy, being European guidelines more aggressive. Endoscopic ultrasound can improve guidelines accuracy in patients with moderate-risk features.
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16.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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17.
  • Sathyendranath, Shubha, et al. (författare)
  • An Ocean-Colour Time Series for Use in Climate Studies : The Experience of the Ocean-Colour Climate Change Initiative (OC-CCI)
  • 2019
  • Ingår i: Sensors. - : MDPI AG. - 1424-8220. ; 19:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Ocean colour is recognised as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS); and spectrally-resolved water-leaving radiances (or remote-sensing reflectances) in the visible domain, and chlorophyll-a concentration are identified as required ECV products. Time series of the products at the global scale and at high spatial resolution, derived from ocean-colour data, are key to studying the dynamics of phytoplankton at seasonal and inter-annual scales; their role in marine biogeochemistry; the global carbon cycle; the modulation of how phytoplankton distribute solar-induced heat in the upper layers of the ocean; and the response of the marine ecosystem to climate variability and change. However, generating a long time series of these products from ocean-colour data is not a trivial task: algorithms that are best suited for climate studies have to be selected from a number that are available for atmospheric correction of the satellite signal and for retrieval of chlorophyll-a concentration; since satellites have a finite life span, data from multiple sensors have to be merged to create a single time series, and any uncorrected inter-sensor biases could introduce artefacts in the series, e.g., different sensors monitor radiances at different wavebands such that producing a consistent time series of reflectances is not straightforward. Another requirement is that the products have to be validated against in situ observations. Furthermore, the uncertainties in the products have to be quantified, ideally on a pixel-by-pixel basis, to facilitate applications and interpretations that are consistent with the quality of the data. This paper outlines an approach that was adopted for generating an ocean-colour time series for climate studies, using data from the MERIS (MEdium spectral Resolution Imaging Spectrometer) sensor of the European Space Agency; the SeaWiFS (Sea-viewing Wide-Field-of-view Sensor) and MODIS-Aqua (Moderate-resolution Imaging Spectroradiometer-Aqua) sensors from the National Aeronautics and Space Administration (USA); and VIIRS (Visible and Infrared Imaging Radiometer Suite) from the National Oceanic and Atmospheric Administration (USA). The time series now covers the period from late 1997 to end of 2018. To ensure that the products meet, as well as possible, the requirements of the user community, marine-ecosystem modellers, and remote-sensing scientists were consulted at the outset on their immediate and longer-term requirements as well as on their expectations of ocean-colour data for use in climate research. Taking the user requirements into account, a series of objective criteria were established, against which available algorithms for processing ocean-colour data were evaluated and ranked. The algorithms that performed best with respect to the climate user requirements were selected to process data from the satellite sensors. Remote-sensing reflectance data from MODIS-Aqua, MERIS, and VIIRS were band-shifted to match the wavebands of SeaWiFS. Overlapping data were used to correct for mean biases between sensors at every pixel. The remote-sensing reflectance data derived from the sensors were merged, and the selected in-water algorithm was applied to the merged data to generate maps of chlorophyll concentration, inherent optical properties at SeaWiFS wavelengths, and the diffuse attenuation coefficient at 490 nm. The merged products were validated against in situ observations. The uncertainties established on the basis of comparisons with in situ data were combined with an optical classification of the remote-sensing reflectance data using a fuzzy-logic approach, and were used to generate uncertainties (root mean square difference and bias) for each product at each pixel.
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18.
  • Valente, Roberto, et al. (författare)
  • The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up
  • 2022
  • Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 22:4, s. 516-524
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown.AIM: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up.MATERIALS AND METHODS: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts).RESULTS: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT.CONCLUSIONS: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.
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