Publications by authors named "Francesco Salerno"

79 Publications

On the factors influencing the chiroptical response of conjugated polymer thin films.

Chem Commun (Camb) 2021 Sep 28;57(77):9914-9917. Epub 2021 Sep 28.

Chemistry - School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK.

We study the influence of the physical and chemical structure on the chiroptical response of fluorene-based polymeric systems, namely poly(9,9-dioctylfluorene) (PFO) and the donor-acceptor type copolymer poly(9,9-dioctylfluorene--benzothiadiazole) (F8BT). We reveal the significance of electric-magnetic coupling, at both short (molecular-level) and intermediate (delocalised over multiple polymer chains) length scales, on the magnitude of the dissymmetry. These findings provide a framework for the design of new materials with an enhanced chiroptical response.
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http://dx.doi.org/10.1039/d1cc02918eDOI Listing
September 2021

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses.

Results: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Natural optical activity as the origin of the large chiroptical properties in π-conjugated polymer thin films.

Nat Commun 2020 12 1;11(1):6137. Epub 2020 Dec 1.

Centre for Processable Electronics, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.

Polymer thin films that emit and absorb circularly polarised light have been demonstrated with the promise of achieving important technological advances; from efficient, high-performance displays, to 3D imaging and all-organic spintronic devices. However, the origin of the large chiroptical effects in such films has, until now, remained elusive. We investigate the emergence of such phenomena in achiral polymers blended with a chiral small-molecule additive (1-aza[6]helicene) and intrinsically chiral-sidechain polymers using a combination of spectroscopic methods and structural probes. We show that - under conditions relevant for device fabrication - the large chiroptical effects are caused by magneto-electric coupling (natural optical activity), not structural chirality as previously assumed, and may occur because of local order in a cylinder blue phase-type organisation. This disruptive mechanistic insight into chiral polymer thin films will offer new approaches towards chiroptical materials development after almost three decades of research in this area.
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http://dx.doi.org/10.1038/s41467-020-19951-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708482PMC
December 2020

Fullerene Desymmetrization as a Means to Achieve Single-Enantiomer Electron Acceptors with Maximized Chiroptical Responsiveness.

Adv Mater 2021 Jan 23;33(1):e2004115. Epub 2020 Nov 23.

Department of Chemistry and Molecular Sciences Research Hub, Imperial College London, White City Campus, 82 Wood Lane, London, W12 0BZ, UK.

Solubilized fullerene derivatives have revolutionized the development of organic photovoltaic devices, acting as excellent electron acceptors. The addition of solubilizing addends to the fullerene cage results in a large number of isomers, which are generally employed as isomeric mixtures. Moreover, a significant number of these isomers are chiral, which further adds to the isomeric complexity. The opportunities presented by single-isomer, and particularly single-enantiomer, fullerenes in organic electronic materials and devices are poorly understood however. Here, ten pairs of enantiomers are separated from the 19 structural isomers of bis[60]phenyl-C61-butyric acid methyl ester, using them to elucidate important chiroptical relationships and demonstrating their application to a circularly polarized light (CPL)-detecting device. Larger chiroptical responses are found, occurring through the inherent chirality of the fullerene. When used in a single-enantiomer organic field-effect transistor, the potential to discriminate CPL with a fast light response time and with a very high photocurrent dissymmetry factor (g  = 1.27 ± 0.06) is demonstrated. This study thus provides key strategies to design fullerenes with large chiroptical responses for use as chiral components of organic electronic devices. It is anticipated that this data will position chiral fullerenes as an exciting material class for the growing field of chiral electronic technologies.
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http://dx.doi.org/10.1002/adma.202004115DOI Listing
January 2021

Efficacy of Albumin Treatment for Patients with Cirrhosis and Infections Unrelated to Spontaneous Bacterial Peritonitis.

Clin Gastroenterol Hepatol 2020 04 5;18(4):963-973.e14. Epub 2019 Aug 5.

EF Clif, EASL-CLIF Consortium and Grifols Chair, Barcelona, Spain.

Background & Aims: We performed a randomized trial to determine whether albumin should be administered to patients with infections unrelated to spontaneous bacterial peritonitis (SBP).

Methods: We performed a multicenter, open-label trial in which 118 patients with cirrhosis, non-SBP infections, and additional risk factors for poor outcome were randomly assigned to receive antibiotics plus albumin (study group; n = 61) or antibiotics alone (control group; n = 57). The primary outcome was in-hospital mortality; secondary outcomes were effect of albumin on disease course.

Results: There were no significant differences at baseline between groups in results from standard laboratory tests, serum markers of inflammation, circulatory dysfunction, or liver severity scores. However, the combined prevalence of acute on chronic liver failure (ACLF) and kidney dysfunction was significantly higher in the study group (44.3% vs 24.6% in the control group; P = .02), indicating greater baseline overall severity. There was no significant difference in the primary outcome between groups (13.1% in the study group vs 10.5% in the control group; P = .66). Circulatory and renal functions improved in only the study group. A significantly higher proportion of patients in the study group had resolution of ACLF (82.3% vs 33.3% in the control group; P = .03). A significantly lower proportion of patients in the study group developed nosocomial infections (6.6% vs 24.6% in the control group; P = .007).

Conclusions: In a randomized trial of patients with advanced cirrhosis and non-SBP infections, in-hospital mortality was similar between those who received albumin plus antibiotics vs those who received only antibiotics (controls). However, patients given albumin were sicker at baseline and, during the follow-up period, a higher proportion had ACLF resolution and a lower proportion had nosocomial infections. ClinicalTrials.gov no: NCT02034279.
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http://dx.doi.org/10.1016/j.cgh.2019.07.055DOI Listing
April 2020

Inverting the Handedness of Circularly Polarized Luminescence from Light-Emitting Polymers Using Film Thickness.

ACS Nano 2019 Jul 26;13(7):8099-8105. Epub 2019 Jun 26.

Department of Physics and Centre of Plastic Electronics , Imperial College London , South Kensington Campus, London SW7 2AZ , U.K.

The emission of circularly polarized light is central to many applications, including data storage, optical quantum computation, biosensing, environmental monitoring, and display technologies. An emerging method to induce (chiral) circularly polarized (CP) electroluminescence from the active layer of polymer light-emitting diodes (polymer OLEDs; PLEDs) involves blending achiral polymers with chiral small-molecule additives, where the handedness/sign of the CP light is controlled by the absolute stereochemistry of the small molecule. Through the in-depth study of such a system we report an interesting chiroptical property: the ability to tune the sign of CP light as a function of active layer thickness for a fixed enantiomer of the chiral additive. We demonstrate that it is possible to achieve both efficient (4.0 cd/A) and bright (8000 cd/m) CP-PLEDs, with high dissymmetry of emission of both left-handed (LH) and right-handed (RH) light, depending on thickness (thin films, 110 nm: = 0.51, thick films, 160 nm: = -1.05, with the terms "thick" and "thin" representing the upper and lower limits of the thickness regime studied), for the same additive enantiomer. We propose that this arises due to an interplay between localized CP emission originating from molecular chirality and CP light amplification or inversion through a chiral medium. We link morphological, spectroscopic, and electronic characterization in thin films and devices with theoretical studies in an effort to determine the factors that underpin these observations. Through the control of active layer thickness and device architecture, this study provides insights into the mechanisms that result in CP luminescence and high performance from CP-PLEDs, as well as demonstrating new opportunities in CP photonic device design.
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http://dx.doi.org/10.1021/acsnano.9b02940DOI Listing
July 2019

Effects of Albumin Treatment on Systemic and Portal Hemodynamics and Systemic Inflammation in Patients With Decompensated Cirrhosis.

Gastroenterology 2019 07 22;157(1):149-162. Epub 2019 Mar 22.

Department of Gastroenterology, Hospital Ramón y Cajal and CIBERehd, Madrid, Spain.

Background & Aims: We investigated the effect of albumin treatment (20% solution) on hypoalbuminemia, cardiocirculatory dysfunction, portal hypertension, and systemic inflammation in patients with decompensated cirrhosis with and without bacterial infections.

Methods: We performed a prospective study to assess the effects of long-term (12 weeks) treatment with low doses (1 g/kg body weight every 2 weeks) and high doses (1.5 g/kg every week) of albumin on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines, collecting data from 18 patients without bacterial infections (the Pilot-PRECIOSA study). We also assessed the effect of short-term (1 week) treatment with antibiotics alone vs the combination of albumin plus antibiotics (1.5 g/kg on day 1 and 1 g/kg on day 3) on plasma levels of cytokines in biobanked samples from 78 patients with bacterial infections included in a randomized controlled trial (INFECIR-2 study).

Results: Circulatory dysfunction and systemic inflammation were extremely unstable in many patients included in the Pilot-PRECIOSA study; these patients had intense and reversible peaks in plasma levels of renin and interleukin 6. Long-term high-dose albumin, but not low-dose albumin, was associated with normalization of serum level of albumin, improved stability of the circulation and left ventricular function, and reduced plasma levels of cytokines (interleukin 6, granulocyte colony-stimulating factor, interleukin 1 receptor antagonist, and vascular endothelial growth factor) without significant changes in portal pressure. The immune-modulatory effects of albumin observed in the Pilot-PRECIOSA study were confirmed in the INFECIR-2 study. In this study, patients given albumin had significant reductions in plasma levels of cytokines.

Conclusions: In an analysis of data from 2 trials (Pilot-PRECIOSA study and INFECIR-2 study), we found that albumin treatment reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis. These effects might be responsible for the beneficial effects of albumin therapy on outcomes of patients with decompensated cirrhosis. ClinicalTrials.gov, Numbers: NCT00968695 and NCT03451292.
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http://dx.doi.org/10.1053/j.gastro.2019.03.021DOI Listing
July 2019

The influence of nitrogen position on charge carrier mobility in enantiopure aza[6]helicene crystals.

Phys Chem Chem Phys 2019 Feb;21(9):5059-5067

Department of Chemistry, Imperial College London, White City Campus, London W12 0BZ, UK.

The properties of an organic semiconductor are dependent on both the chemical structure of the molecule involved, and how it is arranged in the solid-state. It is challenging to extract the influence of each individual factor, as small changes in the molecular structure often dramatically change the crystal packing and hence solid-state structure. Here, we use calculations to explore the influence of the nitrogen position on the charge mobility of a chiral organic molecule when the crystal packing is kept constant. The transfer integrals for a series of enantiopure aza[6]helicene crystals sharing the same packing were analysed in order to identify the best supramolecular motifs to promote charge carrier mobility. The regioisomers considered differ only in the positioning of the nitrogen atom in the aromatic scaffold. The simulations showed that even this small change in the chemical structure has a strong effect on the charge transport in the crystal, leading to differences in charge mobility of up to one order of magnitude. Some aza[6]helicene isomers that were packed interlocked with each other showed high HOMO-HOMO integrals (up to 70 meV), whilst molecules arranged with translational symmetry generally afforded the highest LUMO-LUMO integrals (40-70 meV). As many of the results are not intuitively obvious, a computational approach provides additional insight into the design of new semiconducting organic materials.
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http://dx.doi.org/10.1039/c8cp07603kDOI Listing
February 2019

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights.

BMC Pulm Med 2018 May 15;18(1):70. Epub 2018 May 15.

Internsive Care Unit, Hospital Morales Meseguer, Múrcia, Spain.

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs.

Methods: A literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017).

Results: In managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out. Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients' therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF.

Conclusions: Despite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients' management, possibly leading to improved outcomes. However, further studies are warranted.
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http://dx.doi.org/10.1186/s12890-018-0643-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952859PMC
May 2018

The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation.

Oncotarget 2017 Dec 8;8(69):113502-113515. Epub 2017 Dec 8.

School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

Clear cell renal cell carcinoma (ccRCC) has a poor prognosis despite novel biological targeted therapies. Tumor aggressiveness and poor survival may correlate with tumor grade at diagnosis and with complex metabolic alterations, also involving glucose and lipid metabolism. However, currently no grade-specific metabolic therapy addresses these alterations. Here we used primary cell cultures from ccRCC of low- and high-grade to investigate the effect on energy state and reduced pyridine nucleotide level, and on viability and proliferation, of specific inhibition of glycolysis with 2-deoxy-D-glucose (2DG), or fatty acid oxidation with Etomoxir. Our primary cultures retained the tissue grade-dependent modulation of lipid and glycogen storage and aerobic glycolysis (Warburg effect). 2DG affected lactate production, energy state and reduced pyridine nucleotide level in high-grade ccRCC cultures, but the energy state only in low-grade. Rather, Etomoxir affected energy state in high-grade and reduced pyridine nucleotide level in low-grade cultures. Energy state and reduced pyridine nucleotide level were evaluated by ATP and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) dye quantification, respectively. 2DG treatment impaired cell proliferation and viability of low-grade ccRCC and normal cortex cultures, whereas Etomoxir showed a cytostatic and cytotoxic effect only in high-grade ccRCC cultures. Our data indicate that in ccRCC the Warburg effect is a grade-dependent feature, and fatty acid oxidation can be activated for different grade-dependent metabolic needs. A possible grade-dependent metabolic therapeutic approach in ccRCC is also highlighted.
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http://dx.doi.org/10.18632/oncotarget.23056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5768342PMC
December 2017

Reply to the diagnostic conundrum of bacterial infections in cirrhotic patients.

Liver Int 2017 09;37(9):1412

Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy.

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http://dx.doi.org/10.1111/liv.13474DOI Listing
September 2017

Antipsychotic prescription and mortality in hospitalized older persons.

Psychogeriatrics 2017 Nov 6;17(6):397-405. Epub 2017 Jun 6.

Bianchi Bonomi Haemophilic and Thrombosis Center, IRCCS Ca' Granda - Policlinico Maggiore Hospital Foundation, Milan, Italy.

Background: Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients.

Methods: We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale.

Results: Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5-9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality.

Conclusion: We found that the prescription of antipsychotic drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short-term antipsychotic prescriptions (for acutely ill patients) may have a different effect than long-term, repeated prescriptions.
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http://dx.doi.org/10.1111/psyg.12263DOI Listing
November 2017

Consensus conference on TIPS management: Techniques, indications, contraindications.

Dig Liver Dis 2017 Feb 29;49(2):121-137. Epub 2016 Oct 29.

Gastroepatologia, AOU Città della Salute e della Scienza, Molinette Hospital, Torino, Italy.

The trans jugular intrahepatic Porto systemic shunt (TIPS) is no longer viewed as a salvage therapy or a bridge to liver transplantation and is currently indicated for a number of conditions related to portal hypertension with positive results in survival. Moreover, the availability of self-expandable polytetrafluoroethylene (PTFE)-covered endoprostheses has dramatically improved the long-term patency of TIPS. However, since the last updated International guidelines have been published (year 2009) new evidence have come, which have open the field to new indications and solved areas of uncertainty. On this basis, the Italian Association of the Study of the Liver (AISF), the Italian College of Interventional Radiology-Italian Society of Medical Radiology (ICIR-SIRM), and the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI) promoted a Consensus Conference on TIPS. Under the auspices of the three scientific societies, the consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Bergamo on June 4th and 5th, 2015. The final statements presented here were graded according to quality of evidence and strength of recommendations and were approved by an independent jury. By highlighting strengths and weaknesses of current indications to TIPS, the recommendations of AISF-ICIR-SIRM-SIAARTI may represent the starting point for further studies.
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http://dx.doi.org/10.1016/j.dld.2016.10.011DOI Listing
February 2017

The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study.

Liver Int 2017 01 22;37(1):71-79. Epub 2016 Jul 22.

Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy.

Background & Aims: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Results: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death.

Conclusions: Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.
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http://dx.doi.org/10.1111/liv.13195DOI Listing
January 2017

E-learning in order to improve drug prescription for hospitalized older patients: a cluster-randomized controlled study.

Br J Clin Pharmacol 2016 07 5;82(1):53-63. Epub 2016 Apr 5.

Laboratory for Quality Assessment of Geriatric Therapies and Services, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.

Aims: The aim of the study was to evaluate the effect of an e-learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients.

Methods: Twenty geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug-drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re-hospitalizations were other secondary outcomes assessed at the 12-month follow-up.

Results: A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87-1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34-1.28) and potentially severe DDI (OR 0.86 95%CI 0.63-1.15) at discharge, nor in mortality rates and incidence of re-hospitalization at 12-month follow-up.

Conclusions: This e-learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population.
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http://dx.doi.org/10.1111/bcp.12922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4917810PMC
July 2016

Obstructive lung function decline and IPF: The dark face of the moon.

Chron Respir Dis 2016 05 1;13(2):204-5. Epub 2016 Feb 1.

Intensive Care and Non Invasive Ventilatory Unit, Hospital Morales Meseguer, Murcia, Spain.

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http://dx.doi.org/10.1177/1479972316628534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734597PMC
May 2016

Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.

BMC Gastroenterol 2015 Nov 25;15:167. Epub 2015 Nov 25.

Hygeia Associates, 17988 Brewer Rd., Grass Valley, California, 95949, USA.

Background: Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes.

Methods: Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose.

Results: Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period.

Conclusions: This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of treatment for type 1 HRS and furnishes guidance for the design of future dose-ranging studies.
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http://dx.doi.org/10.1186/s12876-015-0389-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660686PMC
November 2015

Therapy of the refractory ascites: Total paracentesis vs. TIPS.

Gastroenterol Hepatol 2016 Aug-Sep;39(7):477-80. Epub 2015 Nov 18.

Policlinico IRCCS San Donato, Department of Internal Medicine and Hepatology, University of Milan, Italy. Electronic address:

This revision was aimed to report the evidences on the treatment of patients with cirrhosis and refractory ascites. Mainly, we wished to explore which of the predicting variables could be used to prefer large-volume paracentesis or TIPS.
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http://dx.doi.org/10.1016/j.gastrohep.2015.07.011DOI Listing
December 2017

Gender difference in drug use in hospitalized elderly patients.

Eur J Intern Med 2015 Sep 22;26(7):483-90. Epub 2015 Jul 22.

Scientific Direction, Foundation IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Purpose: The aims of this study were to evaluate whether or not there are gender differences in drug use at hospital admission and prescription at discharge and to evaluate the effect of hospitalization on medication patterns in the elderly.

Method: In-patients aged >65years included in the REPOSI registry during a recruitment period of 3years (2008-2010-2012) were analyzed in order to evaluate drug use at hospital admission and prescription at discharge according to gender.

Results: A total of 3473 patients, 52% women and 48% men, were considered. Polypharmacy (>5 drugs) is more frequent in men both at hospital admission and discharge. At hospital discharge, the number of prescriptions increased in both sexes at all age groups. Neuropsychiatric drugs were significantly more prescribed in women (p<0.0001). At admission men were more likely to be on antiplatelets (41.7% vs 36.7%; p=0.0029), ACE-inhibitors (28.7% vs 24.7%; p=0.0072) and statins (22.9% vs 18.3%; p=0.0008). At discharge, antiplatelets (43.7% vs 37.3%; p=0.0003) and statins (25,2% vs 19.6%; p<0.0001) continued to be prescribed more often in men, while women were given beta-blockers more often than men (21.8% vs 18.9%; p=0.0340). Proton pump inhibitors were the most prescribed drugs regardless of gender. At discharge, the medication pattern did not change according to gender.

Conclusion: Our study showed a gender difference in overall medications pattern in the hospitalized elderly. Hospitalization, while increasing the number of prescriptions, did not change drug distribution by sex.
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http://dx.doi.org/10.1016/j.ejim.2015.07.006DOI Listing
September 2015

Treatment of Spontaneous Bacterial Peritonitis.

Dig Dis 2015 6;33(4):582-5. Epub 2015 Jul 6.

Department of Internal Medicine, Policlinico IRCCS San Donato, University of Milan, San Donato Milanese, Italy.

Spontaneous bacterial peritonitis (SBP) is an infection of patients with cirrhosis and ascites. This peculiarity is due to the frequent intestinal translocation that allows bacteria to cross the intestinal barrier, colonizing the ascitic fluid. In cirrhosis, SBP is inferior only to urinary tract infections. It is prevalently sustained by Gram-negative bacteria such as Escherichia coli and Klebsiella. Risk factors for developing SBP are advanced age, refractory ascites, variceal bleeding, renal failure, low albumin levels (below 2.5 g/ml), bilirubin over 4 mg/dl, Child-Pugh class C and a previous diagnosis of SBP. Thus, this is an indication for a long-term antibiotic prophylaxis with norfloxacin. Renal failure - especially the hepatorenal syndrome - complicates SBP in about 20% of cases independently of the efficacy of the antibiotic therapy. The mortality of these patients is about 90%. Infusion of albumin significantly reduces the incidence of hepatorenal syndrome and consequently the risk of death. Long-term quinolonic prophylaxis as well as increased antibiotic therapies are causing the emergence of multidrug-resistant agents as frequent causes of SBP. In such cases, the antibiotic sensitivity to quinolones is low, and European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam. Collection of blood, urine and ascitic fluid for cultures is important for bacterial recognition, possibly before starting an empirical antibiotic therapy. Indeed, the probability of positive cultures rapidly vanishes when they are performed during already implemented antibiotic administration. It is important to know that a failure of the first-line therapy is associated with an increased probability of death.
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http://dx.doi.org/10.1159/000375358DOI Listing
April 2016

Italian registry of patients with alpha-1 antitrypsin deficiency: general data and quality of life evaluation.

COPD 2015 May;12 Suppl 1:52-7

Centro per la Diagnosi del Deficit Ereditario di Alfa-1 Antitripsina, Laboratorio di Biochimica e Genetica, S. C. Pneumologia, Fondazione IRCCS Policlinico San Matteo, Pavia , Italy.

Alpha1-antitrypsin Deficiency (AATD) is a rare hereditary disorder with an estimated prevalence of about 1/5000 individuals in Italy. Deficient patients are at a higher risk of developing lung emphysema and chronic liver disease. The low estimated prevalence of AATD prompted the establishment of a registry with the aim of learning more about the natural history and the quality of care of these patients. The Italian registry for AATD was established in 1996. In this study, genetic and clinical findings of Italian AATD patients are presented. Moreover, we also evaluated the changes in health-related quality of life (HRQoL) in patients with COPD and AAT deficiency over a three-year period, in relation to augmentation therapy. In a period spanning 18 years (1996-2014) a total of 422 adult subjects with severe AATD were enrolled, namely 258 PI*ZZ, 74 PI*SZ, 4 PI*SS and 86 patients with at least one rare deficient allele. The 21.3% frequency for AATD patients with at least one deficient rare variant is the highest so far recorded in national registries of AATD. The registry data allow a detailed characterization of the natural course of the disease and the level of patient care, as well as confirm the usefulness of early AATD detection.
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http://dx.doi.org/10.3109/15412555.2015.1023393DOI Listing
May 2015

Adherence to antibiotic treatment guidelines and outcomes in the hospitalized elderly with different types of pneumonia.

Eur J Intern Med 2015 Jun 18;26(5):330-7. Epub 2015 Apr 18.

Scientific Direction, IRCCS Ca' Granda Maggiore Hospital Policlinico Foundation, Milan, Italy.

Background: Few studies evaluated the clinical outcomes of Community Acquired Pneumonia (CAP), Hospital-Acquired Pneumonia (HAP) and Health Care-Associated Pneumonia (HCAP) in relation to the adherence of antibiotic treatment to the guidelines of the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) in hospitalized elderly people (65 years or older).

Methods: Data were obtained from REPOSI, a prospective registry held in 87 Italian internal medicine and geriatric wards. Patients with a diagnosis of pneumonia (ICD-9 480-487) or prescribed with an antibiotic for pneumonia as indication were selected. The empirical antibiotic regimen was defined to be adherent to guidelines if concordant with the treatment regimens recommended by IDSA/ATS for CAP, HAP, and HCAP. Outcomes were assessed by logistic regression models.

Results: A diagnosis of pneumonia was made in 317 patients. Only 38.8% of them received an empirical antibiotic regimen that was adherent to guidelines. However, no significant association was found between adherence to guidelines and outcomes. Having HAP, older age, and higher CIRS severity index were the main factors associated with in-hospital mortality.

Conclusions: The adherence to antibiotic treatment guidelines was poor, particularly for HAP and HCAP, suggesting the need for more adherence to the optimal management of antibiotics in the elderly with pneumonia.
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http://dx.doi.org/10.1016/j.ejim.2015.04.002DOI Listing
June 2015

Use of non-selective beta blockers in cirrhosis: the evidence we need before closing (or not) the window.

World J Gastroenterol 2015 Feb;21(8):2265-8

Vincenzo La Mura, Francesco Salerno, U.O. Medicina Interna, IRCCS-San Donato, Dipartimento di Scienze Biomediche per la Salute, Università degli studi di Milano, 20097 Milan, Italy.

Non selective beta blockers (NSBBs) are used in primary and secondary prophylaxis of portal hypertension-related bleeding in patients with cirrhosis. The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venous pressure gradient (HVPG) below 12 mmHg or at least 20% of the basal value. Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up; this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis. Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis. These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs: the "window hypothesis". According with this hypothesis, patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis. Indeed, in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death. Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.
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http://dx.doi.org/10.3748/wjg.v21.i8.2265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342901PMC
February 2015

Coagulation and fibrosis: A potential non-negligible target of statins in chronic hepatitis.

J Hepatol 2015 Jul 26;63(1):277-8. Epub 2015 Feb 26.

Unit of Internal Medicine, IRCCS San Donato, San Donato Milanese (MI), University of Milan, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2015.02.027DOI Listing
July 2015

Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: A randomized trial.

Hepatology 2015 Aug 13;62(2):567-74. Epub 2015 Feb 13.

Department of Medicine, DIMED, Padua, Italy.

Unlabelled: Hepatorenal syndrome (HRS), a serious complication of cirrhosis, is associated with high mortality without treatment. Terlipressin with albumin is effective in the reversal of HRS. Where terlipressin is not available, as in the United States, midodrine and octreotide with albumin are used as an alternative treatment of HRS. The aim was to compare the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of HRS in a randomized controlled trial. Twenty-seven patients were randomized to receive terlipressin with albumin (TERLI group) and 22 to receive midodrine and octreotide plus albumin (MID/OCT group). The TERLI group received terlipressin by intravenous infusion, initially 3 mg/24 hours, progressively increased to 12 mg/24 hours if there was no response. The MID/OCT group received midodrine orally at an initial dose of 7.5 mg thrice daily, with the dose increased to a maximum of 12.5 mg thrice daily, together with octreotide subcutaneously: initial dose 100 μg thrice daily and up to 200 μg thrice daily. Both groups received albumin intravenously 1 g/kg of body weight on day 1 and 20-40 g/day thereafter. There was a significantly higher rate of recovery of renal function in the TERLI group (19/27, 70.4%) compared to the MID/OCT group (6/21, 28.6%), P = 0.01. Improvement in renal function and lower baseline Model for End-Stage Liver Disease score were associated with better survival.

Conclusion: Terlipressin plus albumin is significantly more effective than midodrine and octreotide plus albumin in improving renal function in patients with HRS.
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http://dx.doi.org/10.1002/hep.27709DOI Listing
August 2015

Gout, allopurinol intake and clinical outcomes in the hospitalized multimorbid elderly.

Eur J Intern Med 2014 Nov 22;25(9):847-52. Epub 2014 Oct 22.

Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.

Background: Increased serum uric acid has been considered a cardiovascular risk factor but no study has assessed its relation with hospital mortality or length of stay. On the basis of data obtained from a prospective registry, the prevalence of gout/hyperuricemia and its association with these and other clinical parameters was evaluated in an Italian cohort of elderly patients acutely admitted to internal medicine or geriatric wards.

Methods: While the prevalence of gout was calculated by counting patients with this diagnosis hyperuricemia was inferred in patients taking allopurinol at hospital admission or discharge, on the assumption that this drug was only prescribed owing to the finding of high serum levels of uric acid. A series of clinical and demographic variables were evaluated for their association with gout/hyperuricemia.

Results: Of 1380 patients, 139 (10%) had a diagnosis of gout or were prescribed allopurinol. They had more co-morbidities (7.0 vs 5.6; P<0.0001) and consumed more drugs (6.8 vs 5.0; P<0.0001). The CIRS (co-morbidity index) was worse in these patients (OR 1.28 95% CI 1.15-1.41). Multivariable regression analysis showed that only renal and heart failures were independently associated with gout/allopurinol intake. Moreover, this combined event was associated with an increased risk of adverse events during hospitalization (OR 1.66, 95% CI 1.16-2.36), but not with the risk of re-hospitalization, length of hospital stay or death.

Conclusions: Gout/allopurinol intake has a high prevalence in elderly patients acutely admitted to hospital and are associated with renal and cardiovascular diseases, an increased rate of adverse events and a high degree of drug consumption. In contrast, this finding did not affect the length of hospitalization nor hospital mortality.
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http://dx.doi.org/10.1016/j.ejim.2014.09.019DOI Listing
November 2014

The stigma of low opioid prescription in the hospitalized multimorbid elderly in Italy.

Intern Emerg Med 2015 Apr 24;10(3):305-13. Epub 2014 Sep 24.

Department of Clinical and Experimental Science, University of Brescia Italy, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

The primary aim of this study was to evaluate the prevalence of opioid prescriptions in hospitalized geriatric patients. Other aims were to evaluate factors associated with opioid prescription, and whether or not there was consistency between the presence of pain and prescription. Opioid prescriptions were gathered from the REgistro POliterapie Societa` Italiana di Medicina Interna (REPOSI) data for the years 2008, 2010 and 2012. 1,380 in-patients, 65+ years old, were enrolled in the first registry run, 1,332 in the second and 1,340 in the third. The prevalence of opioid prescription was calculated at hospital admission and discharge. In the third run of the registry, the degree of pain was assessed by means of a numerical scale. The prevalence of patients prescribed with opioids at admission was 3.8% in the first run, 3.6% in the second and 4.1% in the third, whereas at discharge rates were slightly higher (5.8, 5.3, and 6.6%). The most frequently prescribed agents were mild opioids such as codeine and tramadol. The number of total prescribed drugs was positively associated with opioid prescription in the three runs; in the third, dementia and a better functional status were inversely associated with opioid prescription. Finally, as many as 58% of patients with significant pain at discharge were prescribed no analgesic at all. The conservative attitude of Italian physicians to prescribe opioids in elderly patients changed very little between hospital admission and discharge through a period of 5 years. Reasons for such a low opioid prescription should be sought in physicians' and patients' concerns and prejudices.
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http://dx.doi.org/10.1007/s11739-014-1131-2DOI Listing
April 2015

Hepatorenal syndrome type 1 and bacterial infection: a catastrophic association in patients with cirrhosis.

Hepatology 2014 Apr 28;59(4):1239-41. Epub 2014 Feb 28.

Policlinico IRCCS San Donato, Medicina Interna ed Epatologia, Università di Milano, Italy.

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http://dx.doi.org/10.1002/hep.27015DOI Listing
April 2014
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