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1. Budget Impact Analysis of Minimally Invasive versus Open Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Disease: A European Hospital Perspective

Author

Bassani R, Galvain T, Battaglia S, Maheswaran H, Wright G, Kambli A, and Piemontese A

Subjects
spine surgery, incremental cost, budget impact analysis, italy, medical device innovation, health economic model, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract

Roberto Bassani,1 Thibaut Galvain,2 Suzanne Battaglia,3 Hendramoorthy Maheswaran,4 George Wright,5 Ankita Kambli,5 Alessandra Piemontese3 1II Spinal Surgery Unit, IRCCS Galeazzi-Sant’Ambrogio Hospital, Milano, Italy; 2Johnson and Johnson MedTech, Issy-les-Moulineaux, France; 3Johnson and Johnson MedTech, Pomezia, Italy; 4Johnson and Johnson MedTech, London, UK; 5EVERSANA, Burlington, Ontario, CanadaCorrespondence: George Wright, EVERSANA, 113-3228 South Service Road, Burlington, Ontario, L7N 3H8, Canada, Tel +1 513-827-3035, Email george.wright@eversana.comPurpose: When traditional therapies fail to provide relief from debilitating lower back pain, surgeries such as transforaminal lumbar interbody fusion (TLIF) may be required. This budget impact analysis (BIA) compared minimally-invasive (MI)-TLIF versus open (O)-TLIF for single-level fusion from an Italian hospital perspective.Methods: The BIA compared costs of 100 MI-TLIF and 100 O-TLIF procedures from an Italian hospital perspective over a one-year time horizon. The base case included costs for length of hospital stay (LOS), blood loss, and sterilizing surgical trays. The scenario analysis also included operating room (OR) time and complication costs. Base case inputs were from the Miller et al meta-analysis; scenario analysis inputs were from the Hammad et al meta-analysis. The device costs for MI-TLIF and O-TLIF procedures were from Italian tender prices for Viper Prime™ System and Expedium™ Spine System, respectively.Results: Base case deterministic analysis results showed cost savings of € 207,370 for MI-TLIF compared with O-TLIF. MI-TLIF costs were lower for LOS (€ 215,277), transfusion for blood loss (€ 16,881), and surgical tray sterilization (€ 28,232), whereas device costs were lower for O-TLIF (€ 53,020). The probabilistic result was similar, with MI-TLIF resulting in savings of € 211,026 (95% credible interval [CR]: € 208,725 – € 213,327). All 1000 base case probabilistic sensitivity analysis runs were cost saving. Deterministic scenario analysis results showed cost savings of € 166,719 for MI-TLIF. MI-TLIF costs were lower for LOS (€ 190,813), transfusion for blood loss (€ 16,881), surgical tray sterilization (€ 28,232), and complications (€ 2076), whereas O-TLIF costs were lower for OR time (€ 18,263) and devices used (€ 53,020).Conclusion: Despite the increase incremental cost for medical device innovation and OR time, this study demonstrates the economic savings of MI-TLIF compared to O-TLIF from a European hospital perspective. The findings will be useful to policy and hospital decision makers in assessing purchasing, funding and reimbursement decisions.Keywords: spine surgery, incremental cost, budget impact analysis, Italy, medical device innovation, health economic model

Published
2024

2. Preoperative management of children with esophageal atresia: current perspectives

Author

Parolini F, Bulotta AL, Battaglia S, and Alberti D

Subjects
Prenatal diagnosis, Esophageal Atresia, Tracheo-esophageal fistula, Ultrasound Scan, Tracheobronchoscopy, Pediatrics, RJ1-570
Abstract

Filippo Parolini,1 Anna Lavinia Bulotta,1 Sonia Battaglia,1 Daniele Alberti1,2 1Department of Pediatric Surgery, “Spedali Civili” Children’s Hospital, 2Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy Abstract: Esophageal atresia remains one of the most challenging congenital anomalies of the newborn. In recent years, because of the advances in prenatal diagnosis, neonatal critical care, and surgical procedures, overall outcomes have improved substantially, including for premature children. Nowadays, most of the research is focused on medium- and long-term morbidity, with particular reference to respiratory and gastroesophageal problems; the high frequency of late sequelae in esophageal atresia warrants regular and multidisciplinary checkups throughout adulthood. Surprisingly, there are few studies on the impact of prenatal diagnosis and there is continuing debate over the prenatal and preoperative management of these complex patients. In this review, we analyze the literature surrounding current knowledge on the management of newborns affected by esophageal atresia, focusing on prenatal management and preoperative assessment. Keywords: prenatal diagnosis, esophageal atresia, tracheoesophageal fistula, ultrasound scan, tracheobronchoscopy

Published
2017

3. The use of ICS/LABA (extra-fine and non-extra-fine) in elderly asthmatics

Author

Benfante A, Basile M, Battaglia S, Spatafora M, and Scichilone N

Subjects
aging, comorbidity, lung function, inhaled corticosteroids, long-acting beta-2 agonists, asthma treatment., Therapeutics. Pharmacology, RM1-950
Abstract

Alida Benfante, Marco Basile, Salvatore Battaglia, Mario Spatafora, Nicola Scichilone Biomedical Department of Internal and Specialist Medicine, University of Palermo, Palermo, Italy Abstract: Age represents an exclusion criterion in randomized clinical trials designed to test the efficacy and safety of inhaled drugs in asthma. As a consequence, data on efficacy and safety of inhaled corticosteroid (ICS) and long-acting ß2 agonist (LABA) combinations in elderly asthmatics are scanty. Older age is associated with an increased proportion of comorbid conditions; in addition, all organ functions undergo a process of senescence, thus reducing their ability to metabolize the agents. Overall, these age-associated conditions may variably, and often unpredictably, affect the metabolism and excretion of respiratory drugs. However, pharmacological treatment of asthma does not follow specific recommendations in the elderly. In the elderly, the ICS/LABA combinations may carry an increased risk of local indesiderable effects, primarily due to the lack of coordination between activation of the device and inhalation, and systemic adverse events, mainly due to the greater amount of active drug that is available because of the age-associated changes in organ functions as well as drug-to-drug and drug-to-concomitant disease interactions. The extra-fine formulations of ICSs/LABAs, which allow for a more favorable drug deposition in the lungs at a reduced dose, may contribute to overcome this issue. This review revises the efficacy and safety of treatment with ICSs/LABAs, focusing on the main pharmacodynamic and pharmacokinetic properties of the drugs and highlighting the potential risks in the elderly asthmatic population. Keywords: aging, comorbidity, lung function, inhaled corticosteroids, long-acting ß2 agonists, asthma treatment

Published
2016

4. Safety and efficacy of montelukast as adjunctive therapy for treatment of asthma in elderly patients

Author

Scichilone N, Battaglia S, Benfante A, and Bellia V

Subjects
Leukotriene, asthma treatment, airway inflammation, aging, Geriatrics, RC952-954.6
Abstract

Nicola Scichilone, Salvatore Battaglia, Alida Benfante, Vincenzo BelliaDipartimento Biomedico di Medicina Interna e Specialistica, University of Palermo, Palermo, ItalyAbstract: Asthma is a disease of all ages. This assumption has been challenged in the past, because of several cultural and scientific biases. A large body of evidence has accumulated in recent years to confirm that the prevalence of asthma in the most advanced ages is similar to that in younger ages. Asthma in the elderly may show similar functional and clinical characteristics to that occurring in young adults, although the frequent coexistence of comorbid conditions in older patients, together with age-associated changes in the human lung, may lead to more severe forms of the disease. Management of asthma in the elderly follows specific guidelines that apply to all ages, although most behaviors are pure extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. This review focuses specifically on the safety and efficacy of leukotriene modifiers, which represent a valid option in the treatment of allergic asthma, both as an alternative to first-line drugs and as add-on treatment to inhaled corticosteroids. Available studies specifically addressing the role of montelukast in the elderly are scarce; however, leukotriene modifiers have been demonstrated to be safe in this age group, even though cases of acute hepatitis and occurrence of Churg-Strauss syndrome have been described in elderly patients; whether this is associated with age is to be confirmed. Furthermore, leukotriene modifiers provide additional benefit when added to regular maintenance therapy, not differently from young asthmatics. In elderly patients, the simpler route of administration of leukotriene modifiers, compared with the inhaled agents, could represent a more effective strategy in improving the outcomes of asthma therapy, given that unintentional nonadherence with inhalation therapy represents a complex problem that may lead to significant impairment of asthma symptom control.Keywords: leukotriene antagonists, asthma, treatment, airway inflammation, aging

Published
2013

5. Lung penetration and patient adherence considerations in the management of asthma: role of extra fine formulations

Author

Scichilone N, Spatafora M, Battaglia S, Arrigo R, Benfante A, and Bellia V

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Nicola Scichilone, Mario Spatafora, Salvatore Battaglia, Rita Arrigo, Alida Benfante, Vincenzo BelliaDipartimento di Biomedicina e Medicina Interna e Specialistica, Sezione di Pneumologia, University of Palermo, Palermo, ItalyAbstract: The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite® technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment.Keywords: asthma, small airways, inflammation, quality of life, device

Published
2013

6. Diagnosis of airway obstruction in the elderly: contribution of the SARA study

Author

Sorino C, Battaglia S, Scichilone N, Pedone C, Antonelli-Incalzi R, Sherrill D, and Bellia V

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Claudio Sorino,1,2 Salvatore Battaglia,1 Nicola Scichilone,1 Claudio Pedone,3 Raffaele Antonelli-Incalzi,3 Duane Sherrill,4 Vincenzo Bellia11Biomedical Department of Internal and Specialist Medicine, Section of Pulmonology, University of Palermo, Italy; 2Division of Pulmonology, S Anna Hospital, Como, Italy; 3Chair of Geriatrics, University Campus Bio-Medico, Roma, Italy; 4Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USABackground: The choice between lower limit of normal or fixed value of forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) < 0.70 as the criterion for confirming airway obstruction is an open issue. In this study, we compared the criteria of lower limit of normal and fixed FEV1/FVC for diagnosis of airway obstruction, with a focus on healthy elderly people.Methods: We selected 367 healthy nonsmoking subjects aged 65–93 years from 1971 participants in the population-based SARA (Salute Respiratoria nell’Anziano, Italian for “Respiratory Health in the Elderly”) study, analyzed their spirometric data, and tested the relationship between spirometric indices and anthropometric variables. The lower limit of normal for FEV1/FVC was calculated as the fifth percentile of the normal distribution for selected subjects.Results: While FEV1 and FVC decreased significantly with aging, the relationship between FEV1/FVC and age was not statistically significant in men or women. The lower limit of normal for FEV1/FVC was 0.65 in men and 0.67 in women. Fifty-five participants (15%) had FEV1/FVC < 0.70 and would have been inappropriately classified as obstructed according to the Global Initiative for Obstructive Lung Disease, American Thoracic Society/European Respiratory Society, and Canadian guidelines on chronic obstructive pulmonary disease. By applying different FEV1/FVC thresholds for the different age groups, as previously proposed in the literature, (0.70 for 80 years) the percentage of patients classified as obstructed decreased to 6%. No subjects older than 80 years had an FEV1/FVC < 0.60.Conclusion: The present results confirm the inadequacy of FEV1/FVC < 0.70 as a diagnostic criterion for airway obstruction after the age of 65 years. FEV1/FVC < 0.65 and

Published
2012

7. Anti-inflammatory effects of pre-seasonal Th1-adjuvant vaccine to Parietaria judaica in asthmatics

Author

Scichilone N, Minaldi C, Santagata R, Battaglia S, Camarda G, and Bellia V

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Nicola Scichilone, Chiara Minaldi, Roberta Santagata, Salvatore Battaglia, Gaetana Camarda, Vincenzo Bellia Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), Sezione di Pneumologia, University of Palermo, Palermo, ItalyBackground: The ultra-short course pre-seasonal allergy vaccine, containing appropriate allergoids with the adjuvant monophosphoryl lipid A (MPL), may be effective in treating allergic symptoms. Objective: To explore the timing of the immunological responses to the pre-seasonal allergy vaccine.Methods: Four subcutaneous injections of the active product (Pollinex Quattro) were administered to 20 Parietaria-sensitive intermittent asthmatics (M/F: 12/8; age: 48 ± 10 years; FEV1% predicted: 108% ± 12%) during the 6 weeks prior to the start of the pollen season. Exhaled breath condensate (EBC) was collected immediately before the first and immediately after the last injections (t1 and t2), during the pollen season (t3) and after (t4) the pollen season. EBC was analyzed to determine the levels of pH and 8-isoprostane. Ten Parietaria-sensitive asthmatics served as the untreated control group at t1 and t2.Results: Measured pH levels were 7.64 ± 0.33 at t1, 7.67 ± 0.23 at t2, 7.72 ± 0.34 at t3, and 7.82 ± 0.34 at t4 (P = 0.049 vs baseline). 8-isoprostane levels were significantly lower than baseline at each visit (mean difference from baseline, for t2: —0.77 pg, P = 0.031; for t3: —0.92 pg, P = 0.010; for t4: —0.70 pg, P = 0.048). In the control group, pH levels were 7.73 ± 0.26 at baseline and did not change after 6 weeks (7.79 ± 0.25, P = 0.33). Similarly, the concentrations of 8-isoprostane in the control group were not different from those of the study group at baseline (P = 0.86), and the levels remained unchanged after 6 weeks (P = 0.58).Conclusion: These findings show that the ultra-short course of vaccine adjuvated with MPL acutely reduces the degree of airway inflammation, as expressed by markers of oxidative stress, and suggest that this reduction is maintained during and after the pollen season.Keywords: allergen, asthma, immunotherapy, inflammation, pollen, exhaled breath condensate

Published
2011

11. Diagnostic delay in bronchiectasis: an Italian perspective

Author

Chessarí, C, Simonetta, E, Amati, F, Nigro, M, Stainer, A, Sotgiu, G, Puci, M, Gramegna, A, Blasi, F, Morlacchi, L, Buscemi, A, Conio, V, Sanci, V, Corsico, A, Faverio, P, Michalak, W, Luppi, F, Crimi, C, Vancheri, C, Campisi, R, Vulpi, M, Carpagnano, G, Cicchetti, M, Sekretna, K, Scichilone, N, Battaglia, S, Aliberti, S, Morlacchi, LC, Buscemi, AAMD, Corsico, AG, Vulpi, MR, Carpagnano, GE, Chessarí, C, Simonetta, E, Amati, F, Nigro, M, Stainer, A, Sotgiu, G, Puci, M, Gramegna, A, Blasi, F, Morlacchi, L, Buscemi, A, Conio, V, Sanci, V, Corsico, A, Faverio, P, Michalak, W, Luppi, F, Crimi, C, Vancheri, C, Campisi, R, Vulpi, M, Carpagnano, G, Cicchetti, M, Sekretna, K, Scichilone, N, Battaglia, S, Aliberti, S, Morlacchi, LC, Buscemi, AAMD, Corsico, AG, Vulpi, MR, and Carpagnano, GE

Abstract

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Published
2024

12. Identification of a novel score for adherence to the mediterranean diet that is inversely associated with visceral adiposity and cardiovascular risk: The chrono med diet score (CMDS)

Author

De Matteis, C., primary, Crudele, L., additional, Battaglia, S., additional, Loconte, T., additional, Rotondo, A., additional, Gadaleta, R., additional, Piazzolla, G., additional, Suppressa, P., additional, Sabbà, C., additional, Cariello, M., additional, and Moschetta, A., additional

Published
2023
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14. Hybrid mandibular Bologna midline distractor in combination with surgically assisted rapid maxillary expansion for transverse facial expansion: clinical and cephalometric results

Author

Bianchi, A, Seidita, F, Giudice, R, Pironi, M, Battaglia, S, Crimi, S, and Marchetti, C

Subjects
Distraction osteogenesis, Otorhinolaryngology, Palatal expansion technique, Orthodontics, Orthognathic surgical procedures, Surgery, Mandible, Oral Surgery
Abstract

Transverse maxillomandibular hypoplasia can be treated with surgically assisted rapid maxillary expansion (SARME) in association with mandibular symphyseal distraction (MSD). This paper introduces a hybrid mandibular Bologna midline distractor (BMD); the effectiveness of the distractor in combination with SARME for the treatment of transverse skeletal deficiency was evaluated. This two-centre study included 10 patients with a transverse arch width deficit7 mm and dental crowding, in both the maxilla and mandible, treated with SARME and MSD. The study design was partly retrospective (seven patients) and partly prospective (three patients). Frontal and lateral cephalometric analyses, as well as measurements on dental models, were performed at three different times: before treatment, after the distraction, and 6 months after postoperative orthodontic treatment. The cephalometric analyses and measurements on dental impressions confirmed a balanced and stable skeletal and dental mandibular expansion. An average symphyseal expansion of 7.8 mm was obtained, resolving dental crowding without dental extractions. In conclusion, mandibular expansion performed with the BMD in combination with SARME appears to be a viable surgical approach to transverse maxillomandibular hypoplasia. This technique allows the surgeon to obtain a balanced skeletal and dental expansion, with a low level of relapse.

Published
2023

15. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Author

Sonnenkalb, L, Carter, JJ, Spitaleri, A, Iqbal, Z, Hunt, M, Malone, KM, Utpatel, C, Cirillo, DM, Rodrigues, C, Nilgiriwala, KS, Fowler, PW, Merker, M, Niemann, S, Barilar, I, Battaglia, S, Borroni, E, Brandao, AP, Brankin, A, Cabibbe, AM, Carter, J, Claxton, P, Clifton, DA, Cohen, T, Coronel, J, Crook, DW, Dreyer, V, Earle, SG, Escuyer, V, Ferrazoli, L, Fu Gao, G, Gardy, J, Gharbia, S, Ghisi, KT, Ghodousi, A, Gibertoni Cruz, AL, Grandjean, L, Grazian, C, Groenheit, R, Guthrie, JL, He, W, Hoffmann, H, Hoosdally, SJ, Ismail, NA, Jarrett, L, Joseph, L, Jou, R, Kambli, P, Khot, R, Knaggs, J, Koch, A, Kohlerschmidt, D, Kouchaki, S, Lachapelle, AS, Lalvani, A, Grandjean Lapierre, S, Laurenson, IF, Letcher, B, Lin, W-H, Liu, C, Liu, D, Mandal, A, Mansjö, M, Matias, D, Meintjes, G, De Freitas Mendes, F, Mihalic, M, Millard, J, Miotto, P, Mistry, N, Moore, D, Musser, KA, Ngcamu, D, Hoang, NN, Nimmo, C, Okozi, N, Oliveira, RS, Omar, SV, Paton, N, Peto, TEA, Watanabe Pinhata, JM, Plesnik, S, Puyen, ZM, Rabodoarivelo, MS, Rakotosamimanana, N, Rancoita, PMV, Rathod, P, Rodger, G, Rodwell, TC, Roohi, E, Santos-Lazaro, D, Shah, S, Kohl, TA, Smith, G, Solano, W, Supply, P, Surve, U, Tahseen, S, Thuong, NTT, Thwaites, G, Todt, K, Trovato, A, Van Rie, A, Vijay, S, Walker, TM, Walker, SA, Warren, R, Werngren, J, Wijkander, M, Wilkinson, RJ, Wilson, DJ, Wintringer, P, Yu, XX, Yang, Y, Zhao, Y, Yao, S-Y, Zhu, B, and Consortium, Comprehensive Resistance Prediction for Tuberculosis: an International

Subjects
Microbiology (medical), Infectious Diseases, Virology, Microbiology
Abstract

Background Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Published
2023

16. Network meta-analysis of first-line systemic therapies for advanced hepatocellular carcinoma: Who is the winner?

Author

Celsa, C., primary, Cabibbo, G., additional, Rizzo, G.E.M., additional, Giuffrida, P., additional, Enea, M., additional, Di Maria, G., additional, Antonucci, M., additional, Giacchetto, C.M., additional, Rancatore, G., additional, Grassini, M.V., additional, Ciccia, R., additional, Grova, A., additional, Salvato, M., additional, Battaglia, S., additional, Vaccaro, M., additional, and Cammà, C., additional

Published
2023
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17. Serum procalcitonin predicts mortality independently of the presence of ACLF in patients with cirrhosis and ascites hospitalized for suspicious infection and treated with empiric antibiotic therapy

Author

Bianchini, M., primary, Celsa, C., additional, Magro, B., additional, Cavani, G., additional, Giuffrida, P., additional, Battaglia, S., additional, Saltini, D., additional, Zanetto, A., additional, Indulti, F., additional, Guasconi, T., additional, Girardis, M., additional, Calvaruso, V., additional, Fagiuoli, S., additional, Colecchia, A., additional, Villa, E., additional, Cammà, C., additional, and Schepis, F., additional

Published
2023
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18. OC.08.2 NETWORK META-ANALYSIS OF FIRST-LINE SYSTEMIC THERAPIES FOR ADVANCED HEPATOCELLULAR CARCINOMA: WHO IS THE WINNER?

Author

Celsa, C., primary, Cabibbo, G., additional, Rizzo, G.E.M., additional, Giuffrida, P., additional, Di Maria, G., additional, Battaglia, S., additional, Vaccaro, M., additional, Enea, M., additional, Giacchetto, C., additional, Rancatore, G., additional, Grassini, M., additional, Ciccia, R., additional, Grova, A., additional, Salvato, M., additional, and Camma, C., additional

Published
2023
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24. Bedaquiline and clofazimine resistance in Mycobacterium tuberculosis: an in-vitro and in-silico data analysis

Author

Sonnenkalb, Lindsay, Carter, Joshua James, Spitaleri, Andrea, Iqbal, Zamin, Hunt, Martin, Malone, Kerri Marie, Utpatel, Christian, Cirillo, Daniela Maria, Rodrigues, Camilla, Nilgiriwala, Kayzad Soli, Fowler, Philip William, Merker, Matthias, Niemann, Stefan, Consortium, The Comprehensive Resistance Prediction for Tuberculosis: an International, Barilar, I, Battaglia, S, Borroni, E, Brandao, AP, Brankin, A, Cabibbe, AM, Carter, J, Claxton, P, Clifton, DA, Cohen, T, Coronel, J, Crook, DW, Dreyer, V, Earle, SG, Escuyer, V, Ferrazoli, L, Fowler, PW, Gao, G Fu, Gardy, J, Gharbia, S, Ghisi, KT, Ghodousi, A, Cruz, AL Gibertoni, Grandjean, L, Grazian, C, Groenheit, R, Guthrie, JL, He, W, Hoffmann, H, Hoosdally, SJ, Ismail, NA, Jarrett, L, Joseph, L, Jou, R, Kambli, P, Khot, R, Knaggs, J, Koch, A, Kohlerschmidt, D, Kouchaki, S, Lachapelle, AS, Lalvani, A, Lapierre, S Grandjean, Laurenson, IF, Letcher, B, Lin, WH, Liu, C, Liu, D, Malone, KM, Mandal, A, Mansjö, M, Matias, D, Meintjes, G, de Freitas Mendes, F, Mihalic, M, Millard, J, Miotto, P, Mistry, N, Moore, D, Musser, KA, Ngcamu, D, Hoang, NN, Nimmo, C, Okozi, N, Oliveira, RS, Omar, SV, Paton, N, Peto, TE, Pinhata, JM Watanabe, Plesnik, S, Puyen, ZM, Rabodoarivelo, MS, Rakotosamimanana, N, Rancoita, PM, Rathod, P, Rodger, G, Rodwell, TC, Roohi, E, Santos-Lazaro, D, Shah, S, Kohl, TA, Smith, G, Solano, W, Supply, P, Surve, U, Tahseen, S, and Thuong, NTT

Subjects
Model organisms, Human Biology & Physiology, FOS: Clinical medicine, Immunology, Infectious Disease
Abstract

Background: Bedaquiline is a core drug for the treatment of multidrug-resistant tuberculosis; however, the understanding of resistance mechanisms is poor, which is hampering rapid molecular diagnostics. Some bedaquiline-resistant mutants are also cross-resistant to clofazimine. To decipher bedaquiline and clofazimine resistance determinants, we combined experimental evolution, protein modelling, genome sequencing, and phenotypic data. Methods: For this in-vitro and in-silico data analysis, we used a novel in-vitro evolutionary model using subinhibitory drug concentrations to select bedaquiline-resistant and clofazimine-resistant mutants. We determined bedaquiline and clofazimine minimum inhibitory concentrations and did Illumina and PacBio sequencing to characterise selected mutants and establish a mutation catalogue. This catalogue also includes phenotypic and genotypic data of a global collection of more than 14 000 clinical Mycobacterium tuberculosis complex isolates, and publicly available data. We investigated variants implicated in bedaquiline resistance by protein modelling and dynamic simulations. Findings: We discerned 265 genomic variants implicated in bedaquiline resistance, with 250 (94%) variants affecting the transcriptional repressor (Rv0678) of the MmpS5–MmpL5 efflux system. We identified 40 new variants in vitro, and a new bedaquiline resistance mechanism caused by a large-scale genomic rearrangement. Additionally, we identified in vitro 15 (7%) of 208 mutations found in clinical bedaquiline-resistant isolates. From our in-vitro work, we detected 14 (16%) of 88 mutations so far identified as being associated with clofazimine resistance and also seen in clinically resistant strains, and catalogued 35 new mutations. Structural modelling of Rv0678 showed four major mechanisms of bedaquiline resistance: impaired DNA binding, reduction in protein stability, disruption of protein dimerisation, and alteration in affinity for its fatty acid ligand. Interpretation: Our findings advance the understanding of drug resistance mechanisms in M tuberculosis complex strains. We have established an extended mutation catalogue, comprising variants implicated in resistance and susceptibility to bedaquiline and clofazimine. Our data emphasise that genotypic testing can delineate clinical isolates with borderline phenotypes, which is essential for the design of effective treatments. Funding: Leibniz ScienceCampus Evolutionary Medicine of the Lung, Deutsche Forschungsgemeinschaft, Research Training Group 2501 TransEvo, Rhodes Trust, Stanford University Medical Scientist Training Program, National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Bill & Melinda Gates Foundation, Wellcome Trust, and Marie Skłodowska-Curie Actions.

Published
2023
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28. Air pollution exposure and prevalence of chronic respiratory diseases in Italy

Author

Miotti, J, primary, Marchetti, P, additional, Locatelli, F, additional, Antonicelli, L, additional, Baldacci, S, additional, Battaglia, S, additional, Bono, R, additional, Corsico, A, additional, Gariazzo, C, additional, Maio, S, additional, Murgia, N, additional, Pirina, P, additional, Stafoggia, M, additional, Torroni, L, additional, Viegi, G, additional, Verlato, G, additional, and Marcon, A, additional

Published
2022
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30. Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients. risk factors and therapeutic implications

Author

Loffredo L., Vidili G., Sciacqua A., Cogliati C., Di Giulio R., Bernardini S., Ciacci P., Pietrangelo A., Orlando F., Paraninfi A., Boddi M., Di Minno G., Falsetti L., Lodigiani C., Santoliquido A., Ettorre E., Pignatelli P., Arezzo M. F., Gutu E., Harenberg J., Violi F., Casciaro M. A., Morelli S., Accapezzato D., Rossi E., Palumbo I. M., Pannunzio A., Fallarino A., Maggio E., Bocchini V. P., Gioia C., Izzo R., Luongo R., Cosenza M., Bisciglia M. F., Battaglia S., Pirillo L. S., Capozza A., Summa M. L., Armentaro G., Volpentesta M., Rullo R., Baldinia L., Arienti V., Meloni P. L., Sauchella A., Melis S., Berria M., Solinas B., Vilardi L., Sarobba P., Pisanu M., Mangatia P., Cringoli M., Blanca D., Casella F., Vegetti A., Crociani A., Donnarumma E., Pacciani G., Rovereto R., Lunardi S., Tufano A., Pacetti V., Domenicali M., Leopoldo P., Ceci F., Loffredo, L., Vidili, G., Sciacqua, A., Cogliati, C., Di Giulio, R., Bernardini, S., Ciacci, P., Pietrangelo, A., Orlando, F., Paraninfi, A., Boddi, M., Di Minno, G., Falsetti, L., Lodigiani, C., Santoliquido, A., Ettorre, E., Pignatelli, P., Arezzo, M. F., Gutu, E., Harenberg, J., Violi, F., Casciaro, M. A., Morelli, S., Accapezzato, D., Rossi, E., Palumbo, I. M., Pannunzio, A., Fallarino, A., Maggio, E., Bocchini, V. P., Gioia, C., Izzo, R., Luongo, R., Cosenza, M., Bisciglia, M. F., Battaglia, S., Pirillo, L. S., Capozza, A., Summa, M. L., Armentaro, G., Volpentesta, M., Rullo, R., Baldinia, L., Arienti, V., Meloni, P. L., Sauchella, A., Melis, S., Berria, M., Solinas, B., Vilardi, L., Sarobba, P., Pisanu, M., Mangatia, P., Cringoli, M., Blanca, D., Casella, F., Vegetti, A., Crociani, A., Donnarumma, E., Pacciani, G., Rovereto, R., Lunardi, S., Tufano, A., Pacetti, V., Domenicali, M., Leopoldo, P., and Ceci, F.

Subjects
anticoagulants, asymptomatic deep venous thrombosis, compression ultrasound, Anticoagulant, medical patient, Hematology, Asymptomatic deep venous thrombosi, Deep venous thrombosi, deep venous thrombosis
Abstract

Background Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. Patients/Methods In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. Results Of 2,100 patients (1002 females, 998 males, age 71 ± 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6–15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. Conclusions We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission. Trial registration NCT03157843.

Published
2022

31. The CORBEL matrix on informed consent in clinical studies: a multidisciplinary approach of Research Infrastructures Building Enduring Life-science Services

Author

Colombo, C, Mayrhofer, M, Kubiak, C, Battaglia, S, Matei, M, Lavitrano, M, Casati, S, Chico, V, Schluender, I, Carapina, T, Mosconi, P, Colombo C., Mayrhofer M. T., Kubiak C., Battaglia S., Matei M., Lavitrano M., Casati S., Chico V., Schluender I., Carapina T., Mosconi P., Colombo, C, Mayrhofer, M, Kubiak, C, Battaglia, S, Matei, M, Lavitrano, M, Casati, S, Chico, V, Schluender, I, Carapina, T, Mosconi, P, Colombo C., Mayrhofer M. T., Kubiak C., Battaglia S., Matei M., Lavitrano M., Casati S., Chico V., Schluender I., Carapina T., and Mosconi P.

Abstract

Background: Informed consent forms for clinical research are several and variable at international, national and local levels. According to the literature, they are often unclear and poorly understood by participants. Within the H2020 project CORBEL—Coordinated Research Infrastructures Building Enduring Life-science Services—clinical researchers, researchers in ethical, social, and legal issues, experts in planning and management of clinical studies, clinicians, researchers in citizen involvement and public engagement worked together to provide a minimum set of requirements for informed consent in clinical studies. Methods: The template was based on a literature review including systematic reviews and guidelines searched on PubMed, Embase, Cochrane Library, NICE, SIGN, GIN, and Clearinghouse databases, and on comparison of templates gathered through an extensive search on the websites of research institutes, national and international agencies, and international initiatives. We discussed the draft versions step-by-step and then we referred to it as the “matrix” to underline its modular character and indicate that it allows adaptation to the context in which it will be used. The matrix was revised by representatives of two international patient groups. Results: The matrix covers the process of ensuring that the appropriate information, context and setting are provided so that the participant can give truly informed consent. It addresses the key topics and proposes wording on how to clarify the meaning of placebo and of non-inferiority studies, the importance of individual participants’ data sharing, and the impossibility of knowing in advance how the data might be used in future studies. Finally, it presents general suggestions on wording, format, and length of the information sheet. Conclusions: The matrix underlines the importance of improving the process of communication, its proper conditions (space, time, setting), and addresses the participants’ lack of knowled

Published
2021

32. Aspiration Risk Factors, Microbiology, and Empiric Antibiotics for Patients Hospitalized With Community-Acquired Pneumonia

Author

Marin-Corral, J, Pascual-Guardia, S, Amati, F, Aliberti, S, Masclans, J, Soni, N, Rodriguez, A, Sibila, O, Sanz, F, Sotgiu, G, Anzueto, A, Dimakou, K, Petrino, R, van de Garde, E, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Adrian Ceccato, V, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Bashi, J, Dodo, R, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Pefura Yone, E, Mbatchou Ngahane, B, Shen, N, Xu, J, Bustamante Rico, C, Buitrago, R, Pereira Paternina, F, Kayembe Ntumba, J, Carevic, V, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Bouchy Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, Baunbaek-knudsen, G, Petersen, P, Andersen, S, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Faverio, P, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Menzella, F, Milani, G, Nava, S, Palmiero, G, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, San Luca, O, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Adefuye Bolanle Olufunlola, O, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Neves, J, Abel, S, Ravara, S, Brocovschii, V, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Ali Bukhary, Z, Edathodu, J, Fathy, A, Abdulaziz Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, S, Milenkovic, B, Pesut, D, Borderias, L, Bordon Garcia, N, Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Interna, M, Gallego, M, Gaspar-GarcIa, I, Gonzalez del Castillo, J, Victoria, P, Martinez, E, Malo de Molina, R, Marcos, P, Menendez, R, Pando-Sandoval, A, Aymerich, C, Lacoma de la Torre, A, Garcia-Olive, I, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Arnauld Attannon Fiogbe, I, Yangui, F, Bilaceroglu, S, Levent Dalar, I, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Hancock, C, Villafuerte, D, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Ricardo, A, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Reyes, L, Angel, L, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Wunderink, R, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, Labra, L, Marin-Corral J., Pascual-Guardia S., Amati F., Aliberti S., Masclans J. R., Soni N., Rodriguez A., Sibila O., Sanz F., Sotgiu G., Anzueto A., Dimakou K., Petrino R., van de Garde E., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Adrian Ceccato V. H. D. C. A., Chertcoff J., Lascar F., Di Tulio F., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Bashi J., Dodo R., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A. D., Pefura Yone E. W., Mbatchou Ngahane B. H., Shen N., Xu J. -F., Bustamante Rico C. A., Buitrago R., Pereira Paternina F. J., Kayembe Ntumba J. -M., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M. -L., Christensen A. B., Heitmann Bodtger U. C., Meyer C. N., Jensen A. V., Baunbaek-knudsen G., Petersen P. T., Andersen S., El-Said Abd El-Wahhab I., Morsy N. E., Shafiek H., Sobh E., Abdulsemed K. A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Faverio P., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M. A., Menzella F., Milani G., Nava S., Palmiero G., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., San Luca O., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Adefuye Bolanle Olufunlola O. N. O., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Abel Salazar, Ravara S. B., Brocovschii V., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z. A., Edathodu J., Fathy A., Abdulaziz Enani A. M., Mohamed N. E., Memon J. U., Bella A., Bogdanovic S. N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N. M., Alarcon H. C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Interna M., Gallego M., Gaspar-GarcIa I., Gonzalez del Castillo J., Victoria P. J., Martinez E. L., Malo de Molina R., Marcos P. J., Menendez R., Pando-Sandoval A., Aymerich C. P., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Arnauld Attannon Fiogbe I. U., Yangui F., Bilaceroglu S., Levent Dalar I. D., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Hancock C., Villafuerte D., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Ricardo A. Franco-Sadud C. J., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C. I., Levine S. M., Reyes L. F., Angel L. F., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Wunderink R. G., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., Labra L., Marin-Corral, J, Pascual-Guardia, S, Amati, F, Aliberti, S, Masclans, J, Soni, N, Rodriguez, A, Sibila, O, Sanz, F, Sotgiu, G, Anzueto, A, Dimakou, K, Petrino, R, van de Garde, E, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Adrian Ceccato, V, Chertcoff, J, Lascar, F, Di Tulio, F, Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Bashi, J, Dodo, R, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Pefura Yone, E, Mbatchou Ngahane, B, Shen, N, Xu, J, Bustamante Rico, C, Buitrago, R, Pereira Paternina, F, Kayembe Ntumba, J, Carevic, V, Jakopovic, M, Jankovic, M, Matkovic, Z, Mitrecic, I, Bouchy Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, Baunbaek-knudsen, G, Petersen, P, Andersen, S, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, de Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Spielmanns, M, Creutz, P, Suttorp, N, Siaw-Lartey, B, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Martin-Loeches, I, Maor, Y, Strahilevitz, J, Faverio, P, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Del Prato, B, De Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Menzella, F, Milani, G, Nava, S, Palmiero, G, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, San Luca, O, Franzetti, F, Carugati, M, Morosi, M, Monge, E, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Adefuye Bolanle Olufunlola, O, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ferrao, C, Neves, J, Abel, S, Ravara, S, Brocovschii, V, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Ali Bukhary, Z, Edathodu, J, Fathy, A, Abdulaziz Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, S, Milenkovic, B, Pesut, D, Borderias, L, Bordon Garcia, N, Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Interna, M, Gallego, M, Gaspar-GarcIa, I, Gonzalez del Castillo, J, Victoria, P, Martinez, E, Malo de Molina, R, Marcos, P, Menendez, R, Pando-Sandoval, A, Aymerich, C, Lacoma de la Torre, A, Garcia-Olive, I, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Arnauld Attannon Fiogbe, I, Yangui, F, Bilaceroglu, S, Levent Dalar, I, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Hancock, C, Villafuerte, D, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Ricardo, A, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Reyes, L, Angel, L, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Wunderink, R, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, Labra, L, Marin-Corral J., Pascual-Guardia S., Amati F., Aliberti S., Masclans J. R., Soni N., Rodriguez A., Sibila O., Sanz F., Sotgiu G., Anzueto A., Dimakou K., Petrino R., van de Garde E., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Adrian Ceccato V. H. D. C. A., Chertcoff J., Lascar F., Di Tulio F., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Bashi J., Dodo R., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A. D., Pefura Yone E. W., Mbatchou Ngahane B. H., Shen N., Xu J. -F., Bustamante Rico C. A., Buitrago R., Pereira Paternina F. J., Kayembe Ntumba J. -M., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Bouchy Jacobsson M. -L., Christensen A. B., Heitmann Bodtger U. C., Meyer C. N., Jensen A. V., Baunbaek-knudsen G., Petersen P. T., Andersen S., El-Said Abd El-Wahhab I., Morsy N. E., Shafiek H., Sobh E., Abdulsemed K. A., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Creutz P., Suttorp N., Siaw-Lartey B., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Faverio P., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Del Prato B., De Rosa M., Fantini R., Fiorentino G., Gammino M. A., Menzella F., Milani G., Nava S., Palmiero G., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., San Luca O., Franzetti F., Carugati M., Morosi M., Monge E., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Adefuye Bolanle Olufunlola O. N. O., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ferrao C., Neves J., Abel Salazar, Ravara S. B., Brocovschii V., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Ali Bukhary Z. A., Edathodu J., Fathy A., Abdulaziz Enani A. M., Mohamed N. E., Memon J. U., Bella A., Bogdanovic S. N., Milenkovic B., Pesut D., Borderias L., Bordon Garcia N. M., Alarcon H. C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Interna M., Gallego M., Gaspar-GarcIa I., Gonzalez del Castillo J., Victoria P. J., Martinez E. L., Malo de Molina R., Marcos P. J., Menendez R., Pando-Sandoval A., Aymerich C. P., Lacoma de la Torre A., Garcia-Olive I., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Arnauld Attannon Fiogbe I. U., Yangui F., Bilaceroglu S., Levent Dalar I. D., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Hancock C., Villafuerte D., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Ricardo A. Franco-Sadud C. J., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C. I., Levine S. M., Reyes L. F., Angel L. F., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Wunderink R. G., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., and Labra L.

Abstract

Background: Aspiration community-acquired pneumonia (ACAP) and community-acquired pneumonia (CAP) in patients with aspiration risk factors (AspRFs) are infections associated with anaerobes, but limited evidence suggests their pathogenic role. Research Question: What are the aspiration risk factors, microbiology patterns, and empiric anti-anaerobic use in patients hospitalized with CAP? Study Design and Methods: This is a secondary analysis of GLIMP, an international, multicenter, point-prevalence study of adults hospitalized with CAP. Patients were stratified into three groups: (1) ACAP, (2) CAP/AspRF+ (CAP with AspRF), and (3) CAP/AspRF- (CAP without AspRF). Data on demographics, comorbidities, microbiological results, and anti-anaerobic antibiotics were analyzed in all groups. Patients were further stratified in severe and nonsevere CAP groups. Results: We enrolled 2,606 patients with CAP, of which 193 (7.4%) had ACAP. Risk factors independently associated with ACAP were male, bedridden, underweight, a nursing home resident, and having a history of stroke, dementia, mental illness, and enteral tube feeding. Among non-ACAP patients, 1,709 (70.8%) had CAP/AspRF+ and 704 (29.2%) had CAP/AspRF-. Microbiology patterns including anaerobes were similar between CAP/AspRF-, CAP/AspRF+ and ACAP (0.0% vs 1.03% vs 1.64%). Patients with severe ACAP had higher rates of total gram-negative bacteria (64.3% vs 44.3% vs 33.3%, P =.021) and lower rates of total gram-positive bacteria (7.1% vs 38.1% vs 50.0%, P <.001) when compared with patients with severe CAP/AspRF+ and severe CAP/AspRF-, respectively. Most patients (>50% in all groups) independent of AspRFs or ACAP received specific or broad-spectrum anti-anaerobic coverage antibiotics. Interpretation: Hospitalized patients with ACAP or CAP/AspRF+ had similar anaerobic flora compared with patients without aspiration risk factors. Gram-negative bacteria were more prevalent in patients with severe ACAP. Despite having similar

Published
2021

33. Predicting in-hospital mortality from Coronavirus Disease 2019: A simple validated app for clinical use

Author

Magro, B, Zuccaro, V, Novelli, L, Zileri, L, Celsa, C, Raimondi, F, Gori, M, Cammà, G, Battaglia, S, Genova, V, Paris, L, Tacelli, M, Mancarella, F, Enea, M, Attanasio, M, Senni, M, Di Marco, F, Lorini, L, Fagiuoli, S, Bruno, R, Cammà, C, Gasbarrini, A, Magro B, Zuccaro V, Novelli L, Zileri L, Celsa C, Raimondi F, Gori M, Cammà G, Battaglia S, Genova VG, Paris L, Tacelli M, Mancarella FA, Enea M, Attanasio M, Senni M, Di Marco F, Lorini LF, Fagiuoli S, Bruno R, Cammà C, Gasbarrini A, Magro, B, Zuccaro, V, Novelli, L, Zileri, L, Celsa, C, Raimondi, F, Gori, M, Cammà, G, Battaglia, S, Genova, V, Paris, L, Tacelli, M, Mancarella, F, Enea, M, Attanasio, M, Senni, M, Di Marco, F, Lorini, L, Fagiuoli, S, Bruno, R, Cammà, C, Gasbarrini, A, Magro B, Zuccaro V, Novelli L, Zileri L, Celsa C, Raimondi F, Gori M, Cammà G, Battaglia S, Genova VG, Paris L, Tacelli M, Mancarella FA, Enea M, Attanasio M, Senni M, Di Marco F, Lorini LF, Fagiuoli S, Bruno R, Cammà C, and Gasbarrini A

Abstract

Backgrounds Validated tools for predicting individual in-hospital mortality of COVID-19 are lacking. We aimed to develop and to validate a simple clinical prediction rule for early identification of in-hospital mortality of patients with COVID-19. Methods and findings We enrolled 2191 consecutive hospitalized patients with COVID-19 from three Italian dedicated units (derivation cohort: 1810 consecutive patients from Bergamo and Pavia units; validation cohort: 381 consecutive patients from Rome unit). The outcome was in-hospital mortality. Fine and Gray competing risks multivariate model (with discharge as a competing event) was used to develop a prediction rule for in-hospital mortality. Discrimination and calibration were assessed by the area under the receiver operating characteristic curve (AUC) and by Brier score in both the derivation and validation cohorts. Seven variables were independent risk factors for in-hospital mortality: age (Hazard Ratio [HR] 1.08, 95% Confidence Interval [CI] 1.07–1.09), male sex (HR 1.62, 95%CI 1.30–2.00), duration of symptoms before hospital admission <10 days (HR 1.72, 95%CI 1.39–2.12), diabetes (HR 1.21, 95% CI 1.02–1.45), coronary heart disease (HR 1.40 95% CI 1.09–1.80), chronic liver disease (HR 1.78, 95%CI 1.16–2.72), and lactate dehydrogenase levels at admission (HR 1.0003, 95%CI 1.0002–1.0005). The AUC was 0.822 (95%CI 0.722–0.922) in the derivation cohort and 0.820 (95%CI 0.724–0.920) in the validation cohort with good calibration. The prediction rule is freely available as a web-app (COVID-CALC: https://sites.google.com/community. unipa.it/covid-19riskpredictions/c19-rp). Conclusions A validated simple clinical prediction rule can promptly and accurately assess the risk for in-hospital mortality, improving triage and the management of patients with COVID-19.

Published
2021

34. As-needed anti-inflammatory reliever therapy for asthma management: evidence and practical considerations

Author

Bianco A., Contoli M., Di Marco F., Saverio Mennini F., Papi A., Ando F., Antonicelli L., Battaglia S., Beghe B., Braido F., Caminati M., Costantino M. T., D'Amato M., Dente F., Di Bona D., Facciolongo N., Fois A., Graziani E., Pelaia G., Poto S., Radovanovic D., Rumi G., Savi E., Schino P., Solidoro P., Bianco A., Contoli M., Di Marco F., Saverio Mennini F., Papi A., Ando F., Antonicelli L., Battaglia S., Beghe B., Braido F., Caminati M., Costantino M.T., D'Amato M., Dente F., Di Bona D., Facciolongo N., Fois A., Graziani E., Pelaia G., Poto S., Radovanovic D., Rumi G., Savi E., Schino P., Solidoro P., Bianco, A., Contoli, M., Di Marco, F., Saverio Mennini, F., Papi, A., Ando, F., Antonicelli, L., Battaglia, S., Beghe, B., Braido, F., Caminati, M., Costantino, M. T., D'Amato, M., Dente, F., Di Bona, D., Facciolongo, N., Fois, A., Graziani, E., Pelaia, G., Poto, S., Radovanovic, D., Rumi, G., Savi, E., Schino, P., and Solidoro, P.

Subjects
0301 basic medicine, Budesonide, medicine.medical_specialty, Immunology, Settore SECS-P/03, Anti-Inflammatory Agents, Socio-culturale, Disease, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Asthma management, asthma, pharmacology and pharmacogenomics, pneumology, 03 medical and health sciences, 0302 clinical medicine, Symptom relief, Maintenance therapy, medicine, Immunology and Allergy, Humans, Anti-Asthmatic Agents, Pneumology, Intensive care medicine, Asthma, Asthma, Pharmacology and pharmacogenomics, Pneumology, business.industry, Inhaler, Pharmacology and pharmacogenomics, Respiratory disease, pharmacology and pharmacogenomic, medicine.disease, respiratory tract diseases, Bronchodilator Agents, 030104 developmental biology, 030228 respiratory system, business, medicine.drug
Abstract

Asthma is a chronic respiratory disease in which airway inflammation is a key feature, even in the milder expressions of the disease. The conventional pharmacological approach to mild asthma has long relied on reliever therapy with as-needed short-acting beta-agonists (SABAs), while anti-inflammatory maintenance with inhaled corticosteroids (ICSs) has been reserved for patients with more persistent asthma. Poor adherence to maintenance treatment is an important issue in asthma management, and can partly explain suboptimal symptom control. Over-reliance on SABA bronchodilators for rapid symptom relief is common in real life and potentially leads to an increased risk of asthma morbidity and mortality. Combined anti-inflammatory and reliever medications in a single inhaler have the potential to overcome these limitations. Recent studies in patients with mild asthma have shown that anti-inflammatory reliever therapy with budesonide-formoterol, given on an as-needed basis, is superior to SABA in ensuring asthma control and non-inferior to budesonide maintenance therapy in preventing exacerbations. To address the implications of these important findings for the management of patients with asthma, Italian specialists convened at a series of meetings held during the second half of 2018 across Italy. This article presents their position on these topics and includes a review of the evidence supporting the use of anti-inflammatory reliever therapy in mild asthma and the implementation of this novel approach in clinical practice.

Published
2021

35. Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia

Author

Villafuerte, D, Aliberti, S, Soni, N, Faverio, P, Marcos, P, Wunderink, R, Rodriguez, A, Sibila, O, Sanz, F, Martin-Loeches, I, Menzella, F, Reyes, L, Jankovic, M, Spielmanns, M, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Ceccato, A, Chertcoff, J, Cordon Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Yone, E, Ngahane, B, Shen, N, Xu, J, Rico, C, Buitrago, R, Paternina, F, Ntumba, J, Carevic, V, Jakopovic, M, Matkovic, Z, Mitrecic, I, Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Creutz, P, Suttorp, N, Siaw-Lartey, B, Dimakou, K, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Maor, Y, Strahilevitz, J, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Prato, B, Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Milani, G, Nava, S, Palmiero, G, Petrino, R, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, Franzetti, F, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, van de Garde, E, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Nwankwo, O, Olufunlola, A, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ravara, S, Brocovschii, V, Ion, C, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Bukhary, Z, Edathodu, J, Fathy, A, Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, N, Milenkovic, B, Pesut, D, Borderias, L, Garcia, N, Cabello Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Gallego, M, Gaspar-Garcia, I, Castillo, J, Victoria, P, Laserna Martinez, E, Molina, R, Menendez, R, Pando-Sandoval, A, Aymerich, C, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Fiogbe, A, Yangui, F, Bilaceroglu, S, Dalar, L, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hancock, C, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Franco-Sadud, R, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Angel, L, Anzueto, A, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, Labra, L, Villafuerte D., Aliberti S., Soni N. J., Faverio P., Marcos P. J., Wunderink R. G., Rodriguez A., Sibila O., Sanz F., Martin-Loeches I., Menzella F., Reyes L. F., Jankovic M., Spielmanns M., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Ceccato A., Chertcoff J., Cordon Diaz A., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A. D., Yone E. W. P., Ngahane B. H. M., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Ntumba J. -M. K., Carevic V. V., Jakopovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., Heitmann Bodtger U. C., Meyer C. N., Jensen A. V., El-Said Abd El-Wahhab I., Morsy N. E., Shafiek H., Sobh E., Abdulsemed K. A., Bertrand F., Brun-Buisson C., Montmollin E. D., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Prato B. D., Rosa M. D., Fantini R., Fiorentino G., Gammino M. A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ravara S. B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z. A. A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N. M. B., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Gallego M., Gaspar-Garcia I., Castillo J. G. D., Victoria P. J., Laserna Martinez E., Molina R. M. D., Menendez R., Pando-Sandoval A., Aymerich C. P., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Hancock C., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Franco-Sadud R. A., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., Labra L., Villafuerte, D, Aliberti, S, Soni, N, Faverio, P, Marcos, P, Wunderink, R, Rodriguez, A, Sibila, O, Sanz, F, Martin-Loeches, I, Menzella, F, Reyes, L, Jankovic, M, Spielmanns, M, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Ceccato, A, Chertcoff, J, Cordon Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Yone, E, Ngahane, B, Shen, N, Xu, J, Rico, C, Buitrago, R, Paternina, F, Ntumba, J, Carevic, V, Jakopovic, M, Matkovic, Z, Mitrecic, I, Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Creutz, P, Suttorp, N, Siaw-Lartey, B, Dimakou, K, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Maor, Y, Strahilevitz, J, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Prato, B, Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Milani, G, Nava, S, Palmiero, G, Petrino, R, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, Franzetti, F, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, van de Garde, E, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Nwankwo, O, Olufunlola, A, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ravara, S, Brocovschii, V, Ion, C, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Bukhary, Z, Edathodu, J, Fathy, A, Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, N, Milenkovic, B, Pesut, D, Borderias, L, Garcia, N, Cabello Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Gallego, M, Gaspar-Garcia, I, Castillo, J, Victoria, P, Laserna Martinez, E, Molina, R, Menendez, R, Pando-Sandoval, A, Aymerich, C, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Fiogbe, A, Yangui, F, Bilaceroglu, S, Dalar, L, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hancock, C, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Franco-Sadud, R, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Angel, L, Anzueto, A, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, Labra, L, Villafuerte D., Aliberti S., Soni N. J., Faverio P., Marcos P. J., Wunderink R. G., Rodriguez A., Sibila O., Sanz F., Martin-Loeches I., Menzella F., Reyes L. F., Jankovic M., Spielmanns M., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Ceccato A., Chertcoff J., Cordon Diaz A., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A. D., Yone E. W. P., Ngahane B. H. M., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Ntumba J. -M. K., Carevic V. V., Jakopovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., Heitmann Bodtger U. C., Meyer C. N., Jensen A. V., El-Said Abd El-Wahhab I., Morsy N. E., Shafiek H., Sobh E., Abdulsemed K. A., Bertrand F., Brun-Buisson C., Montmollin E. D., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Prato B. D., Rosa M. D., Fantini R., Fiorentino G., Gammino M. A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ravara S. B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z. A. A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N. M. B., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Gallego M., Gaspar-Garcia I., Castillo J. G. D., Victoria P. J., Laserna Martinez E., Molina R. M. D., Menendez R., Pando-Sandoval A., Aymerich C. P., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Hancock C., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Franco-Sadud R. A., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., and Labra L.

Abstract

Background and objective: Enterobacteriaceae (EB) spp. family is known to include potentially multidrug-resistant (MDR) microorganisms, and remains as an important cause of community-acquired pneumonia (CAP) associated with high mortality. The aim of this study was to determine the prevalence and specific risk factors associated with EB and MDR-EB in a cohort of hospitalized adults with CAP. Methods: We performed a multinational, point-prevalence study of adult patients hospitalized with CAP. MDR-EB was defined when ≥3 antimicrobial classes were identified as non-susceptible. Risk factors assessment was also performed for patients with EB and MDR-EB infection. Results: Of the 3193 patients enrolled with CAP, 197 (6%) had a positive culture with EB. Fifty-one percent (n = 100) of EB were resistant to at least one antibiotic and 19% (n = 38) had MDR-EB. The most commonly EB identified were Klebsiella pneumoniae (n = 111, 56%) and Escherichia coli (n = 56, 28%). The risk factors that were independently associated with EB CAP were male gender, severe CAP, underweight (body mass index (BMI) < 18.5) and prior extended-spectrum beta-lactamase (ESBL) infection. Additionally, prior ESBL infection, being underweight, cardiovascular diseases and hospitalization in the last 12 months were independently associated with MDR-EB CAP. Conclusion: This study of adults hospitalized with CAP found a prevalence of EB of 6% and MDR-EB of 1.2%, respectively. The presence of specific risk factors, such as prior ESBL infection and being underweight, should raise the clinical suspicion for EB and MDR-EB in patients hospitalized with CAP.

Published
2020

37. A crowd of BashTheBug volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates

Author

Fowler, P.W., Wright, C., Spiers, H., Zhu, T., Baeten, E.M.L., Hoosdally, S.W., Cruz, A.L.G., Roohi, A., Kouchaki, S., Walker, T.M., Peto, T.E.A., Miller, G., Lintott, C., Clifton, D., Crook, D.W., Walker, A.S., Barilar, I., Battaglia, S., Borroni, E., Brandao, A.P., Brankin, A., Cabibbe, A.M., Carter, J., Chetty, D., Cirillo, D.M., Claxton, P., Clifton, D.A., Cohen, T., Coronel, Jorge, Dreyer, V., Earle, S.G., Escuyer, V., Ferrazoli, L., Gao, G.F., Gardy, J., Gharbia, S., Ghisi, K.T., Ghodousi, A., Grandjean, Louis, Grazian, C., Groenheit, R., Guthrie, J.L., He, W., Hoffmann, H., Hoosdally, S.J., Martinhunt, M., Iqbal, Z., Ismail, N.A., Jarrett, L., Joseph, L., Jou, R., Kambli, P., Khot, R., Knaggs, J., Koch, A., Kohlerschmidt, D., Lachapelle, A.S., Lalvani, A., Lapierre, S.G., Laurenson, I.F., Letcher, B., Lin, W.-H., Liu, C., Liu, D., Malone, K.M., Mandal, A., Mansjõ, M., Matias, D., Meintjes, G., Mendes, F.D.F., Merker, M., Mihalic, M., Millard, J., Miotto, P., Mistry, N., Moore, David Alexander James, Musser, K.A., Ngcamu, D., Nhung, H.N., Niemann, S., Nilgiriwala, K.S., Nimmo, C., O’Donnell, M., Okozi, N., Oliveira, R.S., Omar, S.V., Paton, N., Pinhata, J.M.W., Plesnik, S., Puyen, Z.M., Rabodoarivelo, M.S., Rakotosamimanana, N., Rancoita, P.M.V., Rathod, P., Robinson, E., Rodger, G., Rodrigues, C., Rodwell, T.C., Santos-Lazaro, D., Shah, S., Kohl, T.A., Smith, G., Solano, Walter, Spitaleri, A., Supply, P., Steyn, A.J.C., Surve, U., Tahseen, S., Thuong, N.T.T., Thwaites, G., Todt, K., Trovato, A., Utpatel, C., Van Rie, A., Vijay, S., Warren, R., Werngren, J., Wijkander, M., Wilkinson, R.J., Wilson, D.J., Wintringer, P., Xiao, Y.-X., Yang, Y., Yanlin, Z., Yao, S.-Y., Zhu, B., The Zooniverse Volunteer Community, The CRyPTIC Consortium, Community, The Zooniverse Volunteer, Consortium, The CRyPTIC, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Wellcome Trust

Subjects
Volunteers, Model organisms, infectious disease, [SDV]Life Sciences [q-bio], Immunology, Antitubercular Agents, Infectious Disease, Microbial Sensitivity Tests, Zooniverse Volunteer Community, 0601 Biochemistry and Cell Biology, antibiotics, General Biochemistry, Genetics and Molecular Biology, Imaging, minimum inhibitory concentrations, antitubercular drugs, citizen science, M. tuberculosis, Humans, clinical microbiology, Human Biology & Physiology, General Immunology and Microbiology, CRyPTIC Consortium, Prevention, General Neuroscience, FOS: Clinical medicine, microbiology, BashTheBug, Mycobacterium tuberculosis, General Medicine, microdilution plates, Emerging Infectious Diseases, Infectious Diseases, Good Health and Well Being, tuberculosis, 5.1 Pharmaceuticals, photographs, Antimicrobial Resistance, Biochemistry and Cell Biology, Development of treatments and therapeutic interventions, Infection
Abstract

Tuberculosis is a respiratory disease that is treatable with antibiotics. An increasing prevalence of resistance means that to ensure a good treatment outcome it is desirable to test the susceptibility of each infection to different antibiotics. Conventionally, this is done by culturing a clinical sample and then exposing aliquots to a panel of antibiotics, each being present at a pre-determined concentration, thereby determining if the sample isresistant or susceptible to each sample. The minimum inhibitory concentration (MIC) of a drug is the lowestconcentration that inhibits growth and is a more useful quantity but requires each sample to be tested at a range ofconcentrations for each drug. Using 96-well broth micro dilution plates with each well containing a lyophilised pre-determined amount of an antibiotic is a convenient and cost-effective way to measure the MICs of several drugs at once for a clinical sample. Although accurate, this is still an expensive and slow process that requires highly-skilled and experienced laboratory scientists. Here we show that, through the BashTheBug project hosted on the Zooniverse citizen science platform, a crowd of volunteers can reproducibly and accurately determine the MICs for 13 drugs and that simply taking the median or mode of 11-17 independent classifications is sufficient. There is therefore a potential role for crowds to support (but not supplant) the role of experts in antibiotic susceptibility testing.Tuberculosis is a bacterial respiratory infection that kills about 1.4 million people worldwide each year. While antibiotics can cure the condition, the bacterium responsible for this disease

Published
2022

38. Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms

Author

Earle, SG, Wilson, DJ, Barilar, I, Battaglia, S, Cirillo, DM, Clifton, DA, Crook, DW, Fowler, PW, Grazian, C, Hunt, M, Iqbal, Z, Ismail, NA, Knaggs, J, Lachapelle, AS, Merker, M, Mistry, N, Moore, D, Niemann, S, Peto, TEA, Rodrigues, C, Thwaites, G, Walker, AS, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Consortium, CRyPTIC

Subjects
General Immunology and Microbiology, Anti-Infective Agents, General Neuroscience, [SDV]Life Sciences [q-bio], Mutation, Tuberculosis, Multidrug-Resistant, Antitubercular Agents, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Genome-Wide Association Study
Abstract

The emergence of drug-resistant tuberculosis is a major global public health concern that threatens the ability to control the disease. Whole-genome sequencing as a tool to rapidly diagnose resistant infections can transform patient treatment and clinical practice. While resistance mechanisms are well understood for some drugs, there are likely many mechanisms yet to be uncovered, particularly for new and repurposed drugs. We sequenced 10,228 Mycobacterium tuberculosis (MTB) isolates worldwide and determined the minimum inhibitory concentration (MIC) on a grid of 2-fold concentration dilutions for 13 antimicrobials using quantitative microtiter plate assays. We performed oligopeptide- and oligonucleotide-based genome-wide association studies using linear mixed models to discover resistance-conferring mechanisms not currently catalogued. Use of MIC over binary resistance phenotypes increased sample heritability for the new and repurposed drugs by 26% to 37%, increasing our ability to detect novel associations. For all drugs, we discovered uncatalogued variants associated with MIC, including in the Rv1218c promoter binding site of the transcriptional repressor Rv1219c (isoniazid), upstream of the vapBC20 operon that cleaves 23S rRNA (linezolid) and in the region encoding an α-helix lining the active site of Cyp142 (clofazimine, all p < 10−7.7). We observed that artefactual signals of cross-resistance could be unravelled based on the relative effect size on MIC. Our study demonstrates the ability of very large-scale studies to substantially improve our knowledge of genetic variants associated with antimicrobial resistance in M. tuberculosis.

Published
2022

39. Prevalence and risk factors for Enterobacteriaceae in patients hospitalized with community-acquired pneumonia

Author

Villafuerte D., Aliberti S., Soni N. J., Faverio P., Marcos P. J., Wunderink R. G., Rodriguez A., Sibila O., Sanz F., Martin-Loeches I., Menzella F., Reyes L. F., Jankovic M., Spielmanns M., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Ceccato A., Chertcoff J., Cordon Diaz A., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C. A., Van Braeckel E., Vincent J. L., Djimon M. Z., Nouer S. A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A. D., Yone E. W. P., Ngahane B. H. M., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Ntumba J. -M. K., Carevic V. V., Jakopovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., Heitmann Bodtger U. C., Meyer C. N., Jensen A. V., El-Said Abd El-Wahhab I., Morsy N. E., Shafiek H., Sobh E., Abdulsemed K. A., Bertrand F., Brun-Buisson C., Montmollin E. D., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V. M., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A. D., Prato B. D., Rosa M. D., Fantini R., Fiorentino G., Gammino M. A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ravara S. B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C. M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z. A. A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N. M. B., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Gallego M., Gaspar-Garcia I., Castillo J. G. D., Victoria P. J., Laserna Martinez E., Molina R. M. D., Menendez R., Pando-Sandoval A., Aymerich C. P., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F. M., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Feneley A., Hancock C., Hill A. T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Franco-Sadud R. A., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Totten V., Shah R. D., Mateyo K. J., Noriega L., Alvarado E., Aman M., Labra L., Villafuerte, D, Aliberti, S, Soni, N, Faverio, P, Marcos, P, Wunderink, R, Rodriguez, A, Sibila, O, Sanz, F, Martin-Loeches, I, Menzella, F, Reyes, L, Jankovic, M, Spielmanns, M, Restrepo, M, Aruj, P, Attorri, S, Barimboim, E, Caeiro, J, Garzon, M, Cambursano, V, Ceccato, A, Chertcoff, J, Cordon Diaz, A, de Vedia, L, Ganaha, M, Lambert, S, Lopardo, G, Luna, C, Malberti, A, Morcillo, N, Tartara, S, Pensotti, C, Pereyra, B, Scapellato, P, Stagnaro, J, Shah, S, Lotsch, F, Thalhammer, F, Anseeuw, K, Francois, C, Van Braeckel, E, Vincent, J, Djimon, M, Nouer, S, Chipev, P, Encheva, M, Miteva, D, Petkova, D, Balkissou, A, Yone, E, Ngahane, B, Shen, N, Xu, J, Rico, C, Buitrago, R, Paternina, F, Ntumba, J, Carevic, V, Jakopovic, M, Matkovic, Z, Mitrecic, I, Jacobsson, M, Christensen, A, Heitmann Bodtger, U, Meyer, C, Jensen, A, El-Said Abd El-Wahhab, I, Morsy, N, Shafiek, H, Sobh, E, Abdulsemed, K, Bertrand, F, Brun-Buisson, C, Montmollin, E, Fartoukh, M, Messika, J, Tattevin, P, Khoury, A, Ebruke, B, Dreher, M, Kolditz, M, Meisinger, M, Pletz, M, Hagel, S, Rupp, J, Schaberg, T, Creutz, P, Suttorp, N, Siaw-Lartey, B, Dimakou, K, Papapetrou, D, Tsigou, E, Ampazis, D, Kaimakamis, E, Bhatia, M, Dhar, R, D'Souza, G, Garg, R, Koul, P, Mahesh, P, Jayaraj, B, Narayan, K, Udnur, H, Krishnamurthy, S, Kant, S, Swarnakar, R, Limaye, S, Salvi, S, Golshani, K, Keatings, V, Maor, Y, Strahilevitz, J, Battaglia, S, Carrabba, M, Ceriana, P, Confalonieri, M, Monforte, A, Prato, B, Rosa, M, Fantini, R, Fiorentino, G, Gammino, M, Milani, G, Nava, S, Palmiero, G, Petrino, R, Gabrielli, B, Rossi, P, Sorino, C, Steinhilber, G, Zanforlin, A, Franzetti, F, Carone, M, Patella, V, Scarlata, S, Comel, A, Kurahashi, K, Bacha, Z, Ugalde, D, Zuniga, O, Villegas, J, Medenica, M, van de Garde, E, Mihsra, D, Shrestha, P, Ridgeon, E, Awokola, B, Nwankwo, O, Olufunlola, A, Olumide, S, Ukwaja, K, Irfan, M, Minarowski, L, Szymon, S, Froes, F, Leuschner, P, Meireles, M, Ravara, S, Brocovschii, V, Ion, C, Rusu, D, Toma, C, Chirita, D, Dorobat, C, Birkun, A, Kaluzhenina, A, Almotairi, A, Bukhary, Z, Edathodu, J, Fathy, A, Enani, A, Mohamed, N, Memon, J, Bella, A, Bogdanovic, N, Milenkovic, B, Pesut, D, Borderias, L, Garcia, N, Cabello Alarcon, H, Cilloniz, C, Torres, A, Diaz-Brito, V, Casas, X, Gonzalez, A, Fernandez-Almira, M, Gallego, M, Gaspar-Garcia, I, Castillo, J, Victoria, P, Laserna Martinez, E, Molina, R, Menendez, R, Pando-Sandoval, A, Aymerich, C, Rello, J, Moyano, S, Rodrigo-Troyano, A, Sole-Violan, J, Uranga, A, van Boven, J, Torra, E, Pujol, J, Feldman, C, Yum, H, Fiogbe, A, Yangui, F, Bilaceroglu, S, Dalar, L, Yilmaz, U, Bogomolov, A, Elahi, N, Dhasmana, D, Feneley, A, Hancock, C, Hill, A, Rudran, B, Ruiz-Buitrago, S, Campbell, M, Whitaker, P, Youzguin, A, Singanayagam, A, Allen, K, Brito, V, Dietz, J, Dysart, C, Kellie, S, Franco-Sadud, R, Meier, G, Gaga, M, Holland, T, Bergin, S, Kheir, F, Landmeier, M, Lois, M, Nair, G, Patel, H, Reyes, K, Rodriguez-Cintron, W, Saito, S, Noda, J, Hinojosa, C, Levine, S, Angel, L, Anzueto, A, Whitlow, K, Hipskind, J, Sukhija, K, Totten, V, Shah, R, Mateyo, K, Noriega, L, Alvarado, E, Aman, M, Labra, L, University of St Andrews. Infection Group, University of St Andrews. School of Medicine, University of St Andrews. Infection and Global Health Division, Villafuerte D., Aliberti S., Soni N.J., Faverio P., Marcos P.J., Wunderink R.G., Rodriguez A., Sibila O., Sanz F., Martin-Loeches I., Menzella F., Reyes L.F., Jankovic M., Spielmanns M., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Cordon Diaz A., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Anseeuw K., Francois C.A., Van Braeckel E., Vincent J.L., Djimon M.Z., Nouer S.A., Chipev P., Encheva M., Miteva D., Petkova D., Balkissou A.D., Yone E.W.P., Ngahane B.H.M., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Ntumba J.-M.K., Carevic V.V., Jakopovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., Heitmann Bodtger U.C., Meyer C.N., Jensen A.V., El-Said Abd El-Wahhab I., Morsy N.E., Shafiek H., Sobh E., Abdulsemed K.A., Bertrand F., Brun-Buisson C., Montmollin E.D., Fartoukh M., Messika J., Tattevin P., Khoury A., Ebruke B., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Creutz P., Suttorp N., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Kaimakamis E., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Kant S., Swarnakar R., Limaye S., Salvi S., Golshani K., Keatings V.M., Maor Y., Strahilevitz J., Battaglia S., Carrabba M., Ceriana P., Confalonieri M., Monforte A.D., Prato B.D., Rosa M.D., Fantini R., Fiorentino G., Gammino M.A., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Franzetti F., Carone M., Patella V., Scarlata S., Comel A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Leuschner P., Meireles M., Ravara S.B., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Dorobat C.M., Birkun A., Kaluzhenina A., Almotairi A., Bukhary Z.A.A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bella A., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N.M.B., Cabello Alarcon H., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gallego M., Gaspar-Garcia I., Castillo J.G.D., Victoria P.J., Laserna Martinez E., Molina R.M.D., Menendez R., Pando-Sandoval A., Aymerich C.P., Rello J., Moyano S., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F.M., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Feneley A., Hancock C., Hill A.T., Rudran B., Ruiz-Buitrago S., Campbell M., Whitaker P., Youzguin A., Singanayagam A., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Totten V., Shah R.D., Mateyo K.J., Noriega L., Alvarado E., Aman M., Labra L., Villafuerte, D., Aliberti, S., Soni, N. J., Faverio, P., Marcos, P. J., Wunderink, R. G., Rodriguez, A., Sibila, O., Sanz, F., Martin-Loeches, I., Menzella, F., Reyes, L. F., Jankovic, M., Spielmanns, M., Restrepo, M. I., Aruj, P. K., Attorri, S., Barimboim, E., Caeiro, J. P., Garzon, M. I., Cambursano, V. H., Ceccato, A., Chertcoff, J., Cordon Diaz, A., de Vedia, L., Ganaha, M. C., Lambert, S., Lopardo, G., Luna, C. M., Malberti, A. G., Morcillo, N., Tartara, S., Pensotti, C., Pereyra, B., Scapellato, P. G., Stagnaro, J. P., Shah, S., Lotsch, F., Thalhammer, F., Anseeuw, K., Francois, C. A., Van Braeckel, E., Vincent, J. L., Djimon, M. Z., Nouer, S. A., Chipev, P., Encheva, M., Miteva, D., Petkova, D., Balkissou, A. D., Yone, E. W. P., Ngahane, B. H. M., Shen, N., Xu, J. -F., Rico, C. A. B., Buitrago, R., Paternina, F. J. P., Ntumba, J. -M. K., Carevic, V. V., Jakopovic, M., Matkovic, Z., Mitrecic, I., Jacobsson, M. -L. B., Christensen, A. B., Heitmann Bodtger, U. C., Meyer, C. N., Jensen, A. V., El-Said Abd El-Wahhab, I., Morsy, N. E., Shafiek, H., Sobh, E., Abdulsemed, K. A., Bertrand, F., Brun-Buisson, C., Montmollin, E. D., Fartoukh, M., Messika, J., Tattevin, P., Khoury, A., Ebruke, B., Dreher, M., Kolditz, M., Meisinger, M., Pletz, M. W., Hagel, S., Rupp, J., Schaberg, T., Creutz, P., Suttorp, N., Siaw-Lartey, B., Dimakou, K., Papapetrou, D., Tsigou, E., Ampazis, D., Kaimakamis, E., Bhatia, M., Dhar, R., D'Souza, G., Garg, R., Koul, P. A., Mahesh, P. A., Jayaraj, B. S., Narayan, K. V., Udnur, H. B., Krishnamurthy, S. B., Kant, S., Swarnakar, R., Limaye, S., Salvi, S., Golshani, K., Keatings, V. M., Maor, Y., Strahilevitz, J., Battaglia, S., Carrabba, M., Ceriana, P., Confalonieri, M., Monforte, A. D., Prato, B. D., Rosa, M. D., Fantini, R., Fiorentino, G., Gammino, M. A., Milani, G., Nava, S., Palmiero, G., Petrino, R., Gabrielli, B., Rossi, P., Sorino, C., Steinhilber, G., Zanforlin, A., Franzetti, F., Carone, M., Patella, V., Scarlata, S., Comel, A., Kurahashi, K., Bacha, Z. A., Ugalde, D. B., Zuniga, O. C., Villegas, J. F., Medenica, M., van de Garde, E. M. W., Mihsra, D. R., Shrestha, P., Ridgeon, E., Awokola, B. I., Nwankwo, O. N. O., Olufunlola, A. B., Olumide, S., Ukwaja, K. N., Irfan, M., Minarowski, L., Szymon, S., Froes, F., Leuschner, P., Meireles, M., Ravara, S. B., Brocovschii, V., Ion, C., Rusu, D., Toma, C., Chirita, D., Dorobat, C. M., Birkun, A., Kaluzhenina, A., Almotairi, A., Bukhary, Z. A. A., Edathodu, J., Fathy, A., Enani, A. M. A., Mohamed, N. E., Memon, J. U., Bella, A., Bogdanovic, N., Milenkovic, B., Pesut, D., Borderias, L., Garcia, N. M. B., Cabello Alarcon, H., Cilloniz, C., Torres, A., Diaz-Brito, V., Casas, X., Gonzalez, A. E., Fernandez-Almira, M. L., Gallego, M., Gaspar-Garcia, I., Castillo, J. G. D., Victoria, P. J., Laserna Martinez, E., Molina, R. M. D., Menendez, R., Pando-Sandoval, A., Aymerich, C. P., Rello, J., Moyano, S., Rodrigo-Troyano, A., Sole-Violan, J., Uranga, A., van Boven, J. F. M., Torra, E. V., Pujol, J. A., Feldman, C., Yum, H. K., Fiogbe, A. A., Yangui, F., Bilaceroglu, S., Dalar, L., Yilmaz, U., Bogomolov, A., Elahi, N., Dhasmana, D. J., Feneley, A., Hancock, C., Hill, A. T., Rudran, B., Ruiz-Buitrago, S., Campbell, M., Whitaker, P., Youzguin, A., Singanayagam, A., Allen, K. S., Brito, V., Dietz, J., Dysart, C. E., Kellie, S. M., Franco-Sadud, R. A., Meier, G., Gaga, M., Holland, T. L., Bergin, S. P., Kheir, F., Landmeier, M., Lois, M., Nair, G. B., Patel, H., Reyes, K., Rodriguez-Cintron, W., Saito, S., Noda, J., Hinojosa, C. I., Levine, S. M., Angel, L. F., Anzueto, A., Whitlow, K. S., Hipskind, J., Sukhija, K., Totten, V., Shah, R. D., Mateyo, K. J., Noriega, L., Alvarado, E., Aman, M., and Labra, L.

Subjects
Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, community-acquired pneumonia, Community-acquired pneumonia, Enterobacteriaceae, multidrug-resistance, prevalence, risk factors, International Cooperation, Multidrug-resistance, Microbial Sensitivity Tests, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Research initiative, E-NDAS, Cohort Studies, SDG 3 - Good Health and Well-being, Prevalence, Humans, Medicine, In patient, Risk factor, Veterans Affairs, health care economics and organizations, Aged, business.industry, Enterobacteriaceae Infections, QR Microbiology, medicine.disease, Drug Resistance, Multiple, humanities, Quality enhancement, QR, Community-Acquired Infections, Hospitalization, Risk factors, risk factor, Family medicine, Female, business, Risk assessment, Cohort study
Abstract

N.J.S. is partially funded by the Department of Veterans Affairs, Quality Enhancement Research Initiative (QUERI) Partnered Evaluation Initiative Grant (HX002263-01A1). Background and objective : Enterobacteriaceae (EB) spp. family is known to include potentially multidrug-resistant (MDR) microorganisms, and remains as an important cause of community-acquired pneumonia (CAP) associated with high mortality. The aim of this study was to determine the prevalence and specific risk factors associated with EB and MDR-EB in a cohort of hospitalized adults with CAP. Methods : We performed a multinational, point-prevalence study of adult patients hospitalized with CAP. MDR-EB was defined when ≥3 antimicrobial classes were identified as non-susceptible. Risk factors assessment was also performed for patients with EB and MDR-EB infection. Results : Of the 3193 patients enrolled with CAP, 197 (6%) had a positive culture with EB. Fifty-one percent (n = 100) of EB were resistant to at least one antibiotic and 19% (n = 38) had MDR-EB. The most commonly EB identified were Klebsiella pneumoniae (n = 111, 56%) and Escherichia coli (n = 56, 28%). The risk factors that were independently associated with EB CAP were male gender, severe CAP, underweight (body mass index (BMI)

Published
2020

40. The Effects of an Acceptance and Commitment-Informed Interdisciplinary Rehabilitation Program for Chronic Airway Diseases on Health Status and Psychological Symptoms

Author

Giusti, E. M., Papazian, B., Manna, C., Giussani, V., Perotti, M., Castelli, F., Battaglia, S., Galli, P., Rossi, A., Re, V., Goulene, K., Castelnuovo, G., Stramba-Badiale, M., Giusti E. M. (ORCID:0000-0001-5767-8785), Manna C., Castelnuovo G. (ORCID:0000-0003-2633-9822), Giusti, E. M., Papazian, B., Manna, C., Giussani, V., Perotti, M., Castelli, F., Battaglia, S., Galli, P., Rossi, A., Re, V., Goulene, K., Castelnuovo, G., Stramba-Badiale, M., Giusti E. M. (ORCID:0000-0001-5767-8785), Manna C., and Castelnuovo G. (ORCID:0000-0003-2633-9822)

Abstract

Background: Chronic airway diseases are prevalent and costly conditions. Interdisciplinary rehabilitation programs that include Acceptance and Commitment-based (ACT) components could be important to tackle the vicious circle linking progression of the disease, inactivity, and psychopathological symptoms. Methods: A retrospective evaluation of routinely collected data of an interdisciplinary rehabilitation program was performed. The program included group sessions including patient education, breathing exercise, occupational therapy and an ACT-based psychological treatment, and individual sessions of physical therapy. Demographic data, clinical characteristics of the patients and the values of outcome variables (health status, quality of life, anxiety, and depression) before treatment, at discharge, at 3 months, and at 6 months were extracted from medical records. Multiple imputation was employed to address missing data. Linear mixed models were employed to assess changes over time. Multivariable logistic regression was performed to assess predictors of a minimum clinically important change of health status from baseline to the 6-months follow-up. Results: Data from 31 patients with chronic obstructive pulmonary disease (COPD) and 12 patients with bronchiectasis were extracted. Health status improved from baseline to discharge to the 3 months follow-up, but not to the 6 months follow-up. Anxiety and depression improved across all the time points. Quality of life did not improve over time. Having a worse health status at baseline and fewer depressive symptoms were significantly associated with achieving a minimum clinically important change of health status at 6 months. The effects of the interdisciplinary program were not different for patients with COPD or with bronchiectasis. Discussion: Interdisciplinary programs including ACT-based components are promising treatments for the rehabilitation of patients with chronic airway diseases.

Published
2022

42. 196: SARCOPENIA AND PATIENT’S BODY COMPOSITION: NEW MORPHOMETRIC TOOLS TO PREDICT CLINICAL OUTCOME AFTER IVOR-LEWIS ESOPHAGECTOMY

Author

Battaglia, S, primary, Cossu, A, additional, Palumbo, D, additional, De Pascale, S, additional, Gualtierotti, M, additional, Vecchiato, M, additional, Parise, P, additional, Puccetti, F, additional, Barbieri, L, additional, Elmore, U, additional, De Cobelli, F, additional, Fumagalli Romario, U, additional, Ferrari, G, additional, Petri, R, additional, and Rosati, R, additional

Published
2022
Full Text
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43. Outcomes of three lines Atezolizumab plus Bevacizumab-based sequential treatment for hepatocellular carcinoma: a simulation model

Author

Celsa, C., primary, Cabibbo, G., additional, Battaglia, S., additional, Giuffrida, P., additional, Rizzo, G.E.M., additional, Grova, M., additional, Giacchetto, C.M., additional, Rancatore, G., additional, Stornello, C., additional, Grassini, M.V., additional, Badalamenti, G., additional, Enea, M., additional, Craxì, A., additional, Di Marco, V., additional, and Cammà, C., additional

Published
2022
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45. Improving perioperative management of surgical sets for trauma surgeries: the 4S approach

Author

Ribes-Iborra J, Segarra B, Cortes-Tronch V, Quintana J, Galvain T, Muehlendyck C, Escalona E, Battaglia S, and Navarrete-Dualde J

Subjects
Surgical tray, Stock management, Perioperative management, Sterility, 4S program, Implants, Safety, Instruments, Surgical set, Standardization
Abstract

Background The perioperative management of the surgical instruments and implants that comprise sets for trauma surgeries has been identified as a complex and resource-intensive activity due to non-standardized inventories, redundant surgical instruments and unnecessary sterilization cycles. The 4S Intelligent Trauma Care program aims to improve perioperative management and thereby reduce environmental impact by utilizing standardized inventories, a sterile implant portfolio, a barcode that enables a digital safety certification, and a digitized restocking service. Objective The objective of this study was to investigate the impact of the introduction of the 4S program for the management of surgical sets in open reduction internal fixation (ORIF) trauma surgeries. Methods This was a single-center, quality improvement study of ORIF trauma surgeries, comparing the current practice (30 procedures) to the procedure following the introduction of the 4S program (30 procedures). The primary outcome was the proportion of procedures requiring only one sterilization cycle. Secondary outcomes were the number of sterilization cycles per procedure, set processing time across departments, total set processing costs, number of missing or damaged implants, number of cleaning cycles per procedure, time taken to assemble containers for sterilization, number of containers entering the autoclave per procedure, environmental impact, number of baskets entering the cleaning machine per procedure, and staff satisfaction. Results Introduction of the 4S program resulted in a reduction in the mean number of sterilization cycles required from 2.1 to 1.0 (p < 0.001). In the current practice, only 30.0% of procedure sets were sterilized within one cycle, compared to 100.0% following introduction of the 4S program (p < 0.001). A reduction in the mean set processing time of 24.1% in the OR and 35.3% in the sterilization department was observed. Mean set processing costs for the current practice were euro81.23, compared to euro50.30 following introduction of the 4S program. Furthermore, following the introduction of the 4S program, procedures were associated with significant reductions in water and electricity usage, and increased staff satisfaction. Conclusions This quality improvement study demonstrates the substantial time and cost savings, positive environmental impact and staff satisfaction that could be achieved by streamlining surgical set management through the 4S program. To our knowledge, this is the first study of this type and our findings may be instructive to other hospitals and surgical specialties.

Published
2022

47. Correction to: Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study (European Journal of Clinical Microbiology & Infectious Diseases, (2020), 39, 8, (1513-1525), 10.1007/s10096-020-03870-3)

Author

Carugati M., Aliberti S., Sotgiu G., Blasi F., Gori A., Menendez R., Encheva M., Gallego M., Leuschner P., Ruiz-Buitrago S., Battaglia S., Fantini R., Pascual-Guardia S., Marin-Corral J., Restrepo M. I., Aruj P. K., Attorri S., Barimboim E., Caeiro J. P., Garzon M. I., Cambursano V. H., Ceccato A., Chertcoff J., Lascar F., Tulio F. D., Diaz A. C., de Vedia L., Ganaha M. C., Lambert S., Lopardo G., Luna C. M., Malberti A. G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P. G., Stagnaro J. P., Shah S., Lotsch F., Thalhammer F., Vincent J. L., Anseeuw K., Francois C. A., Van Braeckel E., Djimon M. Z., Bashi J., Roger D., Nouer S. A., Chipev P., Miteva D., Petkova D., Dodo B. A., Ngahane M., Hugo B., Shen N., Xu J. -F., Rico C. A. B., Buitrago R., Paternina F. J. P., Jean-Marie K. N., Carevic V. V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M. -L. B., Christensen A. B., HeitmannBodtger U. C., Meyer C. N., Jensen A. V., Baunbaek-knudsen G., Petersen P. T., Andersen S., El-Wahhab I. E. -S. A., Morsy N. E., Shafiek H., Sobh E., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M. W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P. A., Mahesh P. A., Jayaraj B. S., Narayan K. V., Udnur H. B., Krishnamurthy S. B., Golshani K., Keatings V. M., Martin-Loeches I., Maor Y., Strahilevitz J., Carrabba M., Ceriana P., Confalonieri M., d'Arminio Monforte A., Del Prato B., De Rosa M., Fiorentino G., Gammino M. A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z. A., Ugalde D. B., Zuniga O. C., Villegas J. F., Medenica M., van de Garde E. M. W., Mihsra D. R., Shrestha P., Ridgeon E., Awokola B. I., Nwankwo O. N. O., Olufunlola A. B., Olumide S., Ukwaja K. N., Irfan M., Minarowski L., Szymon S., Froes F., Meireles M., Ferrao C., Neves J., Ravara S. B., da Beira C., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Abdulbaqi Z., Bukhary A., Edathodu J., Fathy A., Enani A. M. A., Mohamed N. E., Memon J. U., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N. M. B., Alarcon H. C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A. E., Fernandez-Almira M. L., Gaspar-GarcIa I., del Castillo J. G., Victoria P. J., Martinez E. L., de Molina R. M., Marcos P. J., PandoSandova A., Aymerich C. P., del la Torre A. L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J. F., Torra E. V., Pujol J. A., Feldman C., Yum H. K., Fiogbe A. A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D. J., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A. T., Rudran B., Campbell M., Whitaker P., Allen K. S., Brito V., Dietz J., Dysart C. E., Kellie S. M., Franco-Sadud R. A., Meier G., Gaga M., Holland T. L., Bergin S. P., Kheir F., Landmeier M., Lois M., Nair G. B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N. J., Noda J., Hinojosa C. I., Levine S. M., Angel L. F., Anzueto A., Whitlow K. S., Hipskind J., Sukhija K., Wunderink R. G., Shah R. D., Mateyo K. J., Carugati M., Aliberti S., Sotgiu G., Blasi F., Gori A., Menendez R., Encheva M., Gallego M., Leuschner P., Ruiz-Buitrago S., Battaglia S., Fantini R., Pascual-Guardia S., Marin-Corral J., Restrepo M.I., Aruj P.K., Attorri S., Barimboim E., Caeiro J.P., Garzon M.I., Cambursano V.H., Ceccato A., Chertcoff J., Lascar F., Tulio F.D., Diaz A.C., de Vedia L., Ganaha M.C., Lambert S., Lopardo G., Luna C.M., Malberti A.G., Morcillo N., Tartara S., Pensotti C., Pereyra B., Scapellato P.G., Stagnaro J.P., Shah S., Lotsch F., Thalhammer F., Vincent J.L., Anseeuw K., Francois C.A., Van Braeckel E., Djimon M.Z., Bashi J., Roger D., Nouer S.A., Chipev P., Miteva D., Petkova D., Dodo B.A., Ngahane M., Hugo B., Shen N., Xu J.-F., Rico C.A.B., Buitrago R., Paternina F.J.P., Jean-Marie K.N., Carevic V.V., Jakopovic M., Jankovic M., Matkovic Z., Mitrecic I., Jacobsson M.-L.B., Christensen A.B., HeitmannBodtger U.C., Meyer C.N., Jensen A.V., Baunbaek-knudsen G., Petersen P.T., Andersen S., El-Wahhab I.E.-S.A., Morsy N.E., Shafiek H., Sobh E., Bertrand F., Brun-Buisson C., de Montmollin E., Fartoukh M., Messika J., Tattevin P., Dreher M., Kolditz M., Meisinger M., Pletz M.W., Hagel S., Rupp J., Schaberg T., Spielmanns M., Siaw-Lartey B., Dimakou K., Papapetrou D., Tsigou E., Ampazis D., Bhatia M., Dhar R., D'Souza G., Garg R., Koul P.A., Mahesh P.A., Jayaraj B.S., Narayan K.V., Udnur H.B., Krishnamurthy S.B., Golshani K., Keatings V.M., Martin-Loeches I., Maor Y., Strahilevitz J., Carrabba M., Ceriana P., Confalonieri M., d'Arminio Monforte A., Del Prato B., De Rosa M., Fiorentino G., Gammino M.A., Menzella F., Milani G., Nava S., Palmiero G., Petrino R., Gabrielli B., Rossi P., Sorino C., Steinhilber G., Zanforlin A., Kurahashi K., Bacha Z.A., Ugalde D.B., Zuniga O.C., Villegas J.F., Medenica M., van de Garde E.M.W., Mihsra D.R., Shrestha P., Ridgeon E., Awokola B.I., Nwankwo O.N.O., Olufunlola A.B., Olumide S., Ukwaja K.N., Irfan M., Minarowski L., Szymon S., Froes F., Meireles M., Ferrao C., Neves J., Ravara S.B., da Beira C., Brocovschii V., Ion C., Rusu D., Toma C., Chirita D., Birkun A., Kaluzhenina A., Almotairi A., Abdulbaqi Z., Bukhary A., Edathodu J., Fathy A., Enani A.M.A., Mohamed N.E., Memon J.U., Bogdanovic N., Milenkovic B., Pesut D., Borderias L., Garcia N.M.B., Alarcon H.C., Cilloniz C., Torres A., Diaz-Brito V., Casas X., Gonzalez A.E., Fernandez-Almira M.L., Gaspar-GarcIa I., del Castillo J.G., Victoria P.J., Martinez E.L., de Molina R.M., Marcos P.J., PandoSandova A., Aymerich C.P., del la Torre A.L., Garcia-Olive I., Rello J., Moyano S., Sanz F., Sibila O., Rodrigo-Troyano A., Sole-Violan J., Uranga A., van Boven J.F., Torra E.V., Pujol J.A., Feldman C., Yum H.K., Fiogbe A.A., Yangui F., Bilaceroglu S., Dalar L., Yilmaz U., Bogomolov A., Elahi N., Dhasmana D.J., Ions R., Skeemer J., Woltmann G., Hancock C., Hill A.T., Rudran B., Campbell M., Whitaker P., Allen K.S., Brito V., Dietz J., Dysart C.E., Kellie S.M., Franco-Sadud R.A., Meier G., Gaga M., Holland T.L., Bergin S.P., Kheir F., Landmeier M., Lois M., Nair G.B., Patel H., Reyes K., Rodriguez-Cintron W., Saito S., Soni N.J., Noda J., Hinojosa C.I., Levine S.M., Angel L.F., Anzueto A., Whitlow K.S., Hipskind J., Sukhija K., Wunderink R.G., Shah R.D., and Mateyo K.J.

Subjects
pneumonia, Settore MED/10 - Malattie Dell'Apparato Respiratorio
Abstract

In the originally published article, the individual collaborator names were not captured under the group name “GLIMP Collaborators”. The names are now captured correctly under this group accordingly. The original article has been corrected.

Published
2021

49. Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of

Author

Fowler, P.W., Barilar, I., Battaglia, S., Borroni, E., Brandao, A.P., Brankin, A., Cabibbe, A.M., Carter, J., Cirillo, D.M., Claxton, P., Clifton, D.A., Cohen, T., Coronel, Jorge, Crook, D.W., Dreyer, V., Earle, S.G., Escuyer, V., Ferrazoli, L., Gao, G.F., Gardy, J., Gharbia, S., Ghisi, K.T., Ghodousi, A., Cruz, A.L.G., Grandjean, Louis, Grazian, C., Groenheit, R., Guthrie, J.L., He, W., Hoffmann, H., Hoosdally, S.J., Hunt, M., Iqbal, Z., Ismail, N.A., Jarrett, L., Joseph, L., Jou, R., Kambli, P., Khot, R., Knaggs, J., Koch, A., Kohlerschmidt, D., Kouchaki, S., Lachapelle, A.S., Lalvani, A., Lapierre, S.G., Laurenson, I.F., Letcher, B., Lin, W.-H., Liu, C., Liu, D., Malone, K.M., Mandal, A., Mansjö, M., Matias, D., Meintjes, G., de Freitas Mendes, F., Merker, M., Mihalic, M., Millard, J., Miotto, P., Mistry, N., Moore, David Alexander James, Musser, K.A., Ngcamu, D., Nhung, H.N., Niemann, S., Nilgiriwala, K.S., Nimmo, C., Okozi, N., Oliveira, R.S., Omar, S.V., Paton, N., Peto, T.E.A., Pinhata, J.M.W., Plesnik, S., Puyen, Z.M., Rabodoarivelo, M.S., Rakotosamimanana, N., Rancoita, P.M.V., Rathod, P., Robinson, E., Rodger, G., Rodrigues, C., Rodwell, T.C., Roohi, A., Santos-Lazaro, D., Shah, S., Kohl, T.A., Smith, G., Solano, Walter, Spitaleri, A., Supply, P., Surve, U., Tahseen, S., Thuong, N.T.T., Thwaites, G., Todt, K., Trovato, A., Utpatel, C., Van Rie, A., Vijay, S., Walker, T.M., Walker, A.S., Warren, R., Werngren, J., Wijkander, M., Wilkinson, R.J., Wilson, D.J., Wintringer, P., Xiao, Y.-X., Yang, Y., Yanlin, Z., Yao, S.-Y., Zhu, B., Consoritum, CRyPTIC, Walker, AS, and CRyPTIC Consortium

Subjects
microdilution, Pulmonary and Respiratory Medicine, tuberculosis, Respiratory, M. tuberculosis, Humans, Tuberculosis, Human medicine, infections, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Anti-Bacterial Agents
Abstract

Drug susceptibility testing ofM. tuberculosisis rooted in a binary susceptible/resistant paradigm. While there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate, it is necessary to measure the epidemiological cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis compounds, including bedaquiline and delamanid, derived from 20 637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex, and therefore aphenotypicallywild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined agenotypicallywild-type population and measured the MIC of the 99th percentile by direct measurement andviafitting a Gaussian using interval regression. The proposed ECOFF/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtainedviathe Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs will inform and encourage the more widespread adoption of broth microdilution: this is a cheap culture-based method that tests the susceptibility of 12–14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis.

Published
2021

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