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1. Latent class analysis of imaging and clinical respiratory parameters from patients with COVID-19-related ARDS identifies recruitment subphenotypes

Author: Filippini, DFL, Di Gennaro, E, van Amstel, RBE, Beenen, LFM, Grasso, S, Pisani, L, Bos, LDJ, Smit, MR, Radiology and Nuclear Medicine, ACS - Microcirculation, Amsterdam Neuroscience - Neurovascular Disorders, Intensive Care Medicine, AII - Inflammatory diseases, ACS - Heart failure & arrhythmias, ACS - Pulmonary hypertension & thrombosis, Graduate School, ANS - Neurovascular Disorders, and Pulmonary medicine
Subjects: Positive-Pressure Respiration, Respiratory Distress Syndrome, Phenotypes, Mechanical ventilation, Radiological data, Latent class analysis, Humans, COVID-19, ARDS, Recruitment, Critical Care and Intensive Care Medicine, Retrospective Studies, Respiratory parameters
Abstract: Background Patients with COVID-19-related acute respiratory distress syndrome (ARDS) require respiratory support with invasive mechanical ventilation and show varying responses to recruitment manoeuvres. In patients with ARDS not related to COVID-19, two pulmonary subphenotypes that differed in recruitability were identified using latent class analysis (LCA) of imaging and clinical respiratory parameters. We aimed to evaluate if similar subphenotypes are present in patients with COVID-19-related ARDS. Methods This is the retrospective analysis of mechanically ventilated patients with COVID-19-related ARDS who underwent CT scans at positive end-expiratory pressure of 10 cmH2O and after a recruitment manoeuvre at 20 cmH2O. LCA was applied to quantitative CT-derived parameters, clinical respiratory parameters, blood gas analysis and routine laboratory values before recruitment to identify subphenotypes. Results 99 patients were included. Using 12 variables, a two-class LCA model was identified as best fitting. Subphenotype 2 (recruitable) was characterized by a lower PaO2/FiO2, lower normally aerated lung volume and lower compliance as opposed to a higher non-aerated lung mass and higher mechanical power when compared to subphenotype 1 (non-recruitable). Patients with subphenotype 2 had more decrease in non-aerated lung mass in response to a standardized recruitment manoeuvre (p = 0.024) and were mechanically ventilated longer until successful extubation (adjusted SHR 0.46, 95% CI 0.23–0.91, p = 0.026), while no difference in survival was found (p = 0.814). Conclusions A recruitable and non-recruitable subphenotype were identified in patients with COVID-19-related ARDS. These findings are in line with previous studies in non-COVID-19-related ARDS and suggest that a combination of imaging and clinical respiratory parameters could facilitate the identification of recruitable lungs before the manoeuvre.
Published: 2022
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2. Effect of Rehabilitation Treatments on Disability in Persons With Disorders of Consciousness: A Propensity Score Study

Author: Sattin D., Leonardi M., Nelli B., Bramanti P., Marino S., Ferro S., Basaglia N., Guido D., Dolce G., Lucca L. F, Cortese M. D., Ermio C., Dattilo T. L., Capomolla S., Di Iasi G., Estraneo A., De Tanti A., Maradini N., Piperno R., Ferri A., Basaglia N, Bergonzoni A., Chiavaroli F., Di Marco F., Carli S., Biasutti E., Marin D., Formisano R., Rizza F., Pisarri F. M., Vichi R., D'Urso A., Grillo G., Leto A., Guerrasio M., Taliento C., Napolitano F., Castelli E., Lispi M. L., Diverio M., Barbieri C., Bini P. P., Angelino G., Dada O., Orlandi A., Pistarini C., Pisoni C., Manera M., Compostini A., Aiachini B., Pessina A., Musio A., Colombetti E., Taraschi S., Aluas M., Croci M., Negri M., Zucchella M. A., Guizzetti G. B., Salamone E., De Valle G., Caroppi S. M., Ramorino E., Salina D., Spannocchi G., Strazzer S., Villa F., Guarnerio C., Chiambretto P., Dartizio R., Feller S., Franzoni L., Giunco F., Massironi L., Azimonti R., Marcolli S. S., Meinecke C., Buse G., Marchesi V, Molteni F., Gramigna C., Lanfranchi M., Pisani L., Sozzi M., Borri G., Cannata A. P., Grillo A., Roca S., Locati D., Arenare F., Magnoni A., Perin C., Sussele M., Quintana T. Y., Camici M. E., Magistrelli F., Samueli T., San Felici L., Manganelli F., Vignati M., Bellanova L., Cattaneo N., Ferraro F., Olgiati E., Brizioli E., Vallasciani M., Gironelli L., Calderisi E., Novelli A., Scaramuzzo R., Perino C., Forno R., Zamponi E., Corna S., Ferrario S., Lamberti G., Rosso S., Colonna F., Navarro J., Trabacca A., Gennaro L., Bertolini A., Addante L., Amenduni M. T., Fiore P., Amoruso M. T., Colella D., Angelillo M. T., Melis G., Desogus G., Baglieri A., Galardi G., Sant'Angelo A., Posteraro F., Forte F., Logi F., Potenza F., Lino M., Zaccara G., Ragazzoni A., Chiaramonti R., March A., Grober G., Kaczor M., Zelger P, Mazzini N., Monti A., Zampolini M., Scarponi F., Avesani R., Salvi L., Tonin P., Cosentino E., Furlanetto N., Bordin M., Martinuzzi A., Buffoni M., Boldrini P., Semerjian M., Sattin, D, Leonardi, M, Nelli, B, Bramanti, P, Marino, S, Ferro, S, Basaglia, N, Guido, D, Dolce, G, Lucca, L, Cortese, M, Ermio, C, Dattilo, T, Capomolla, S, Di Iasi, G, Estraneo, A, De Tanti, A, Maradini, N, Piperno, R, Ferri, A, Bergonzoni, A, Chiavaroli, F, Di Marco, F, Carli, S, Biasutti, E, Marin, D, Formisano, R, Rizza, F, Pisarri, F, Vichi, R, D'Urso, A, Grillo, G, Leto, A, Guerrasio, M, Taliento, C, Napolitano, F, Castelli, E, Lispi, M, Diverio, M, Barbieri, C, Bini, P, Angelino, G, Dada, O, Orlandi, A, Pistarini, C, Pisoni, C, Manera, M, Compostini, A, Aiachini, B, Pessina, A, Musio, A, Colombetti, E, Taraschi, S, Aluas, M, Croci, M, Negri, M, Zucchella, M, Guizzetti, G, Salamone, E, De Valle, G, Caroppi, S, Ramorino, E, Salina, D, Spannocchi, G, Strazzer, S, Villa, F, Guarnerio, C, Chiambretto, P, Dartizio, R, Feller, S, Franzoni, L, Giunco, F, Massironi, L, Azimonti, R, Marcolli, S, Meinecke, C, Buse, G, Marchesi, V, Molteni, F, Gramigna, C, Lanfranchi, M, Pisani, L, Sozzi, M, Borri, G, Cannata, A, Grillo, A, Roca, S, Locati, D, Arenare, F, Magnoni, A, Perin, C, Sussele, M, Quintana, T, Camici, M, Magistrelli, F, Samueli, T, San Felici, L, Manganelli, F, Vignati, M, Bellanova, L, Cattaneo, N, Ferraro, F, Olgiati, E, Brizioli, E, Vallasciani, M, Gironelli, L, Calderisi, E, Novelli, A, Scaramuzzo, R, Perino, C, Forno, R, Zamponi, E, Corna, S, Ferrario, S, Lamberti, G, Rosso, S, Colonna, F, Navarro, J, Trabacca, A, Gennaro, L, Bertolini, A, Addante, L, Amenduni, M, Fiore, P, Amoruso, M, Colella, D, Angelillo, M, Melis, G, Desogus, G, Baglieri, A, Galardi, G, Sant'Angelo, A, Posteraro, F, Forte, F, Logi, F, Potenza, F, Lino, M, Zaccara, G, Ragazzoni, A, Chiaramonti, R, March, A, Grober, G, Kaczor, M, Zelger, P, Mazzini, N, Monti, A, Zampolini, M, Scarponi, F, Avesani, R, Salvi, L, Tonin, P, Cosentino, E, Furlanetto, N, Bordin, M, Martinuzzi, A, Buffoni, M, Boldrini, P, and Semerjian, M
Subjects: Adult, Male, 030506 rehabilitation, medicine.medical_specialty, Propensity score, medicine.medical_treatment, Physical Therapy, Sports Therapy and Rehabilitation, Disorders of consciousness, Severity of Illness Index, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, Clinical Protocols, Severity of illness, medicine, Humans, Longitudinal Studies, Aged, Vegetative state, Rehabilitation, business.industry, Minimally conscious state, Recovery of Function, Disability Rating Scale, Middle Aged, medicine.disease, Treatment Outcome, Italy, Propensity score matching, Physical therapy, Consciousness Disorders, Female, Observational study, 0305 other medical science, business, 030217 neurology & neurosurgery
Abstract: To evaluate the effects of rehabilitation (physical and cognitive) treatments on the diagnosis severity and Disability Rating Scale (DRS) scores, adjusted for a number of potential confounders measured at baseline, in a large cohort of patients with disorders of consciousness across time.An observational, longitudinal (2 evaluations), multicenter project was made in 90 Italian centers.Patients (N=364) with a diagnosis of disorders of consciousness.Primary outcome was the severity of diagnosis, expressed on an ordinal scale (OtherMCSVSdeath). In the Other group were included patients who emerged from an MCS and recovered consciousness. The secondary outcome was the DRS score (range of 0-30 with 30 being the worst value). The DRS is a tool used to define the level of residual disability, commonly used to classify the level of functional impairment in patients with acquired brain injury. Both outcomes were measured for each wave.A total of 364 subjects having a complete set of demographic, clinical, and pharmacologic data were included in the propensity score (PS) analysis. Results showed that the rehabilitation treatments (physical and cognitive) reduced the clinical worsening over time in both severity diagnosis and DRS (around 6.5 points) in patients with disorders of consciousness across different propensity score strategies (ie, PS matching, PS adjustment, and PS-weighted procedures). In addition, cognitive protocols seem to be limited to patients with a median value of DRS=23.Our propensity score analysis suggests that rehabilitation treatment protocols seem effective and should be applied to a broader spectrum of patients with disorders of consciousness.
Published: 2020
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3. Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study

Author: Schuijt, Michiel T. U., Schultz, Marcus J., Paulus, Frederique, Serpa Neto, Ary, van Akkeren, J. P., Algera, A. G., Algoe, C. K., van Amstel, R. B., Baur, O. L., van de Berg, P., Bergmans, D. C. J. J., van den Bersselaar, D. I., Bertens, F. A., Bindels, A. J. G. H., de Boer, M. M., Boer, S. den, Boers, L. S., Bogerd, M., Bos, L. D. J., Botta, M., Breel, J. S., de Bruin, H., de Bruin, S., Bruna, C. L., Buiteman-Kruizinga, L. A., Cremer, O., Determann, R. M., Dongelmans, D. A., de Graaff, M. J., Hol, L., Hollmann, M. W., Horn, J., Juffermans, N. P., Kho, E., de Klerk, E. S., Kuiper, M. A., van Meenen, D. M., Mazzinari, Guido, van Mourik, N., Paulus, F., Pillay, J., Pisani, L., Purmer, I. M., Schultz, M. J., Neto, A. Serpa, Spronk, P. E., Stilma, W., Tuinman, P. R., Vlaar, A. P. J., van Velzen, P., Group, PRoVENT–COVID Collaborative, Critical Care, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, Nursing, AII - Infectious diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, ACS - Heart failure & arrhythmias, Anesthesiology, APH - Quality of Care, ANS - Neuroinfection & -inflammation, AII - Inflammatory diseases, 06 Operations Centre and intensive care, ARD - Amsterdam Reproduction and Development, Center of Experimental and Molecular Medicine, ACS - Microcirculation, APH - Global Health, ACS - Diabetes & metabolism, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: MA Arts Assistenten IC (9), Intensive Care, MUMC+: MA Medische Staf IC (9), Pulmonary medicine, and Intensive care medicine
Subjects: Male, ARDS, CLINICAL-COURSE, ademnood syndroom, Critical Care and Intensive Care Medicine, Acute respiratory failure, Cohort Studies, Clinical endpoint, Medicine, OUTCOMES, Respiratory Distress Syndrome, COVID-19/mortality, Coronavirus disease 2019, Delta P, Respiration, Tidal Volume/physiology, Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, Mortality/trends, Cohort, Driving pressure, Breathing, Cardiology, Female, NEW-YORK-CITY, Cohort study, Respiratory Distress Syndrome/mortality, ΔP, medicine.medical_specialty, Critical Illness, Mechanical power of ventilation, Artificial/mortality, Internal medicine, sterfte, INJURY, Tidal Volume, Humans, kunstmatige beademing, Mortality, Aged, Retrospective Studies, Mechanical power, RC86-88.9, business.industry, Proportional hazards model, Research, COVID-19, Retrospective cohort study, medicine.disease, respiration, artificial/mortality, Respiration, Artificial, Confidence interval, MECHANICAL VENTILATION, Invasive ventilation, Critical Illness/mortality, ICU, business
Abstract: Background The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. Methods We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. Results In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88–1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01–1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01–1.30]; P = 0.028). Conclusions In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).
Published: 2022
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4. Flow Index accurately identifies breaths with low or high inspiratory effort during pressure support ventilation

Author: Albani, F, Fusina, F, Ciabatti, G, Pisani, L, Lippolis, V, Franceschetti, ME, Giovannini, A, di Mussi, R, Murgolo, F, Rosano, A, Grasso, S, Natalini, G, and Intensive care medicine
Subjects: Positive-pressure respiration, Intensive care units, RC86-88.9, Research, Respiration, Medical emergencies. Critical care. Intensive care. First aid, Critical Care and Intensive Care Medicine, Respiration, Artificial, Artificial respiration, Tidal Volume, Humans, Inspiratory effort, Lung, Patient-ventilator interaction
Abstract: Background Flow Index, a numerical expression of the shape of the inspiratory flow-time waveform recorded during pressure support ventilation, is associated with patient inspiratory effort. The aim of this study was to assess the accuracy of Flow Index in detecting high or low inspiratory effort during pressure support ventilation and to establish cutoff values for the Flow index to identify these conditions. The secondary aim was to compare the performance of Flow index,of breathing pattern parameters and of airway occlusion pressure (P0.1) in detecting high or low inspiratory effort during pressure support ventilation. Methods Data from 24 subjects was included in the analysis, accounting for a total of 702 breaths. Breaths with high inspiratory effort were defined by a pressure developed by inspiratory muscles (Pmusc) greater than 10 cmH2O while breaths with low inspiratory effort were defined by a Pmusc lower than 5 cmH2O. The areas under the receiver operating characteristic curves of Flow Index and respiratory rate, tidal volume,respiratory rate over tidal volume and P0.1 were analyzed and compared to identify breaths with low or high inspiratory effort. Results Pmusc, P0.1, Pressure Time Product and Flow Index differed between breaths with high, low and intermediate inspiratory effort, while RR, RR/VT and VT/kg of IBW did not differ in a statistically significant way. A Flow index higher than 4.5 identified breaths with high inspiratory effort [AUC 0.89 (CI 95% 0.85–0.93)], a Flow Index lower than 2.6 identified breaths with low inspiratory effort [AUC 0.80 (CI 95% 0.76–0.83)]. Conclusions Flow Index is accurate in detecting high and low spontaneous inspiratory effort during pressure support ventilation.
Published: 2021
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5. The management of epilepsy in clinical practice: Do the timing and severity of the disease influence the priorities of patients and the caring physicians? Data from the EPINEEDS study

Author: Enia, G., Giussani, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., Lattanzi, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Enia, G, Giussani, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, Lattanzi, S, La, N, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Concordance, Need, Disease, Epilepsy, Needs, Patients, Physicians, Priorities, Newly diagnosed epilepsy, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Seizures, Anticonvulsant, medicine, Humans, 030212 general & internal medicine, Young adult, Aged, Aged, 80 and over, Patient, Prioritie, business.industry, Middle Aged, Caregiver, medicine.disease, Seizure, Clinical Practice, Caregivers, Italy, Neurology, Physician, Recurrent seizures, Family medicine, Population study, Anticonvulsants, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Human
Abstract: Objective The objective of this study was to assess the priorities of patients with epilepsy and their caring physicians with reference to the timing and severity of the disease. Methods This is a national survey in which patients with epilepsy followed in 21 Italian epilepsy centers, and their caring physicians were asked to fill anonymous questionnaires to collect data on different aspects of the disease and their needs and priorities in its management. The collected information included demographics, clinical profile and diagnosis, treatment and outcome of epilepsy. The questions were designed to understand the expectations of the patients and their caring physicians and verify the degree of concordance between patient and doctor. The study population was divided in six prognostic categories: (1) Newly diagnosed epilepsy; (2) Absence of seizures for at least 2 years; (3) Absence of seizures for at least 1 year or occasional seizures; (4) Nondrug-resistant recurrent seizures; (5) drug-resistant seizures; (6) surgical candidate. Results Of the 787 patients enrolled, 432 were women and 355 men aged 15 to 88 years (median 41 years). Disease duration ranged from 6 months to 75 years. The sample included 53 patients with newly diagnosed epilepsy, 283 without seizures for at least 2 years, 162 seizure-free for at least 1 year or with occasional seizures, 123 with nondrug-resistant recurrent seizures, 128 with drug-resistant seizures, and 38 surgical candidates. Significant differences were found between patients and physicians in terms of priorities and needs with reference to the management of the disease. While physicians tend to prioritize the information on the diagnosis and treatment of epilepsy depending on timing and severity, patients focus on the search of the cause, the side effects of drugs, and the effects of any new treatment on the control of seizures regardless of the prognostic category. In addition, physicians tend to undervalue the communication of specific information, like the risk of sudden unexpected death in epilepsy (SUDEP) or the existence of lay associations, which might be of special interest for selected categories of patients. Significance Differences between patients with epilepsy and their caring physicians in terms of needs and priorities and suboptimal communication call for the implementation of programs aimed at addressing the factors deemed most relevant by patients and caregivers for the management of the disease.
Published: 2021
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6. Point-of-care lung ultrasound for the detection of pulmonary manifestations of malaria and sepsis: An observational study

Author: Leopold, S, Ghose, A, Plewes, K, Mazumder, S, Pisani, L, Kingston, H, Paul, S, Barua, A, Sattar, M, Huson, M, Walden, A, Henwood, P, Riviello, E, Schultz, M, Day, N, Kumar Dutta, A, White, N, Dondorp, A, AII - Infectious diseases, Graduate School, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, and ACS - Microcirculation
Subjects: Adult, Male, Critical Care and Emergency Medicine, Pulmonology, Imaging Techniques, Science, Point-of-Care Systems, Research and Analysis Methods, Pathology and Laboratory Medicine, Severity of Illness Index, Diagnostic Radiology, Signs and Symptoms, Respiratory Failure, Diagnostic Medicine, Sepsis, Ultrasound Imaging, Medicine and Health Sciences, Parasitic Diseases, Edema, Humans, Prospective Studies, Acute Respiratory Distress Syndrome, Lung, Ultrasonography, Protozoans, Bangladesh, Respiratory Distress Syndrome, Radiology and Imaging, Organisms, Malarial Parasites, Biology and Life Sciences, Eukaryota, Tropical Diseases, Pulmonary Imaging, Parasitic Protozoans, Malaria, Oxygen, Chemistry, Physical Sciences, Medicine, Female, Research Article, Chemical Elements
Abstract: Introduction Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis. Materials and methods Serial point-of-care lung ultrasound studies were performed on four consecutive days in a planned sub study of an observational cohort of patients with malaria or sepsis in Bangladesh. We quantified aeration patterns across 12 lung regions. ARDS was defined according to the Kigali Modification of the Berlin Definition. Results Of 102 patients enrolled, 71 had sepsis and 31 had malaria. Normal lung ultrasound findings were observed in 44 patients on enrolment and associated with 7% case fatality. ARDS was detected in 10 patients on enrolment and associated with 90% case fatality. All patients with ARDS had sepsis, 4 had underlying pneumonia. Two patients developing ARDS during hospitalisation already had reduced aeration patterns on enrolment. The SpO2/FiO2 ratio combined with the number of regions with reduced aeration was a strong prognosticator for mortality in patients with sepsis (AUROC 91.5% (95% Confidence Interval: 84.6%-98.4%)). Conclusions This study demonstrates the potential usefulness of point-of-care lung ultrasound to detect lung abnormalities in patients with malaria or sepsis in a resource-constrained hospital setting. LUS was highly feasible and allowed to accurately identify patients at risk of death in a resource limited setting.
Published: 2018

7. Potent inhibitors of human LAT1 (SLC7A5) transporter based on dithiazole and dithiazine compounds for development of anticancer drugs

Author: Napolitano, L., Scalise, M., Koyioni, Maria G., Koutentis, Panayiotis Andreas, Catto, M., Eberini, I., Parravicini, C., Palazzolo, L., Pisani, L., Galluccio, M., Console, L., Carotti, A., Indiveri, C., Koutentis, Panayiotis Andreas [0000-0002-4652-7567], and Koyioni, Maria [0000-0002-2786-7523]
Subjects: 0301 basic medicine, Cell Survival, Dithioerythritol, Stereochemistry, Mutant, Thiazines, Antineoplastic Agents, 1,2,4-Dithiazines, Biochemistry, Large Neutral Amino Acid-Transporter 1, 03 medical and health sciences, chemistry.chemical_compound, Residue (chemistry), 0302 clinical medicine, Cell Line, Tumor, Drug Discovery, Humans, Binding site, IC50, Histidine, Cancer, Pharmacology, Dose-Response Relationship, Drug, Molecular Structure, Pharmacological target, Transporter, LAT1 inhibitors, Molecular Docking Simulation, Thiazoles, 1,2,3-Dithiazoles, HEK293 Cells, 030104 developmental biology, chemistry, Covalent bond, 030220 oncology & carcinogenesis, Mechanism of inhibition
Abstract: The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [3H]histidine in exchange with intraliposomal histidine. Out of 59 compounds tested, 8 compounds, showing an inhibition higher than 90% at 100 µM concentration, were subjected to dose-response analysis. Two of them exhibited IC50 lower than 1 µM. Inhibition kinetics, performed on the two best inhibitors, indicated a mixed type of inhibition with respect to the substrate. Furthermore, inhibition of the transporter was still present after removal of the compounds from the reaction mixture, but was reversed on addition of dithioerythritol, a S-S reducing agent, indicating the formation of disulfide(s) between the compounds and the protein. Molecular docking of the two best inhibitors on the hLAT1 homology structural model, highlighted interaction with the substrate binding site and formation of a covalent bond with the residue C407. Indeed, the inhibition was impaired in the hLAT1 mutant C407A confirming the involvement of that Cys residue. Treatment of SiHa cells expressing hLAT1 at relatively high level, with the two most potent inhibitors led to cell death which was not observed after treatment with a compound exhibiting very poor inhibitory effect. © 2017 Elsevier Inc. 143 39 52
Published: 2017

8. Tracheostomy, swallowing disorders and rehabilitation: it is never too late

Author: Gregoretti C., Pisani L., Gregoretti C., and Pisani L.
Subjects: Tracheostomy, Humans, Deglutition Disorders
Published: 2014

9. Migraine-specific quality of life questionnaire and relapse on medication overuse headache

Author: Caproni, S., Bianchi, E., Cupini, L. M., Corbelli, I., Beghi, E., Calabresi, P., Sarchielli, P., Pupillo, E., Pini, L. A., Iani, C., Livrea, P., Prudenzano, M. P., Bernardi, G., Diomedi, M., Tedeschi, G., Russo, A., Pisani, F., Pisani, L. R., Bono, G., Misaggi, G., Di Piero, V., Di Clemente, L., Sandrini, G., and Allena, M.
Subjects: Adult, Male, medicine.medical_specialty, Migraine Disorders, Clinical Neurology, Placebo, Severity of Illness Index, law.invention, Randomized controlled trial, Quality of life, law, Recurrence, Surveys and Questionnaires, Severity of illness, Outcome Assessment, Health Care, medicine, Headache Disorders, Secondary, Humans, Multicenter Studies as Topic, MOH, Relapse, Randomized Controlled Trials as Topic, business.industry, MSQ, Migraine Specific Quality of Life, Ancillary Study, General Medicine, Middle Aged, medicine.disease, moh msq relapse, Settore MED/26 - NEUROLOGIA, Migraine, Physical therapy, Quality of Life, Female, Neurology (clinical), Neurosurgery, business, Research Article
Abstract: Background The management of Medication overuse headache (MOH) represents a difficult challenge for clinicians and headache experts, particularly for the responder rate after a successful withdrawal treatment. The purpose of this study was to investigate the role of demographic and clinical characteristics as well as the score of Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Disability Questionnaire and Leeds Dependence Questionnaire in predicting a response after a successful withdrawal treatment in patients with MOH. Methods This ancillary study is part of a randomized trial that demonstrated the safety and the efficacy of a 3-month treatment with sodium valproate (VPA) (800 mg/day vs placebo) in MOH. Demographic and clinical characteristics and questionnaire results were obtained from the entire sample. Results A significant correlation was found only between MOH relapse and the total MSQ score, the Role Preventive sub-scale and the Emotional Function sub-scale, suggesting a poorer quality of life in non responders. Conclusion A high MSQ score could be associated with a poor short-term outcome in MOH patients after a successful treatment with detoxification followed by a new treatment.
Published: 2015

10. General cognition predicts post-stroke recovery defined through minimal clinically important difference (MCID): a cohort study in an Italian rehabilitation clinic

Author: Ginex, V., Vanacore, N., Lacorte, E., Sozzi, M., Pisani, L., Massimo Corbo, and Clerici, F.
Subjects: Aged, 80 and over, Male, Stroke Rehabilitation, Recovery of Function, Motor Activity, Prognosis, Rehabilitation Centers, Stroke, Disability Evaluation, Cognition, Treatment Outcome, Italy, Risk Factors, Activities of Daily Living, Health Status Indicators, Humans, Female, Physical Therapy Modalities, Aged, Retrospective Studies
Abstract: In the field of rehabilitation it is crucial to define if changes in functional scores correspond to relevant clinical improvements.To assess whether cognition affects motor recovery in post-stroke patients using a clinical meaningful criterion: the minimal clinically important difference (MCID).Retrospective cohort study.Inpatient rehabilitation clinicTwo hundred nine first-ever stroke patients undergoing a post-acute inpatient rehabilitation.Cognitive status was assessed with the cognitive FIM and the Mini-Mental State Examination (MMSE). The response to the rehabilitation was defined as the achievement of the MCID between admission and discharge in the motor FIM (responder) and both in the motor and in the cognitive FIM (best-responder).Subjects with a baseline higher MMSE24.9 had a near four-fold higher probability of being responder (OR 3.91; 95% CI 1.72-8.89) and a two-fold higher probability of being best-responder (OR 2.69; 95% CI 1.24-5.84) on motor FIM as compared to those with a MMSE≤24.9. A duration of the rehabilitation of 55-61 days implies a three-fold higher probability (OR 3.17; 95% CI 1.15-8.72) to be responder as compared to shorter period of treatment; a treatment61 days does not involve a greater probability of response.This is the first study that examined post-stroke motor recovery mainly in terms of clinical relevance (MCID). Subjects with a higher cognitive level are more likely to achieve a clinically meaningful recovery.MCID can be applied extensively to post-stroke patients undergoing to an inpatient rehabilitation in order to have a clinically useful instrument that assess the recovery.
Published: 2014

11. Perceived morbidity and health behaviour in a Dogon community

Author: Coppo P, Keita A, and Pisani L
Subjects: Adult, Male, Program evaluation, Gerontology, medicine.medical_specialty, Health (social science), Adolescent, media_common.quotation_subject, Decision Making, Health Behavior, Population, Medically Underserved Area, Developing country, Mali, History and Philosophy of Science, Hygiene, Environmental health, Epidemiology, medicine, Humans, Child, education, Socioeconomic status, media_common, education.field_of_study, Social perception, business.industry, Public health, Infant, Community Health Centers, Middle Aged, Patient Acceptance of Health Care, Self Care, Socioeconomic Factors, Child, Preschool, Educational Status, Female, Health Services Research, Medicine, Traditional, Morbidity, business
Abstract: The episodes of morbidity over a 6 month period were recorded at 179 households comprising 1715 people living in the district of Bandiagara (Mali). This population was subdivided into groups according to their distances from the nearest district health centre and educational services, their scholarization, socio-economic and hygiene levels. The subjects interviewed were asked to report illnesses using their vernacular names, the type of therapy selected, the decision process, the time-lapse between onset and remedial action, the treatment undergone and its effect. Subsequent analysis of the data recorded indicates that the frequency of morbidity episodes is inversely proportionate to the household's level of hygiene. It also appears that factors such as the household's hygienic, socio-economic and educational levels along with the type of illness and its duration, are more decisive when resorting (or not resorting) to treatment than is the proximity factor. This seems particularly true in the case of traditional medicine, chosen even where cosmopolitan resources are available and by people with a relatively high socioeconomic, hygienic and educational level. In the specific situation under study this paper indicates those areas for further study with a view to improving public health education.
Published: 1992
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12. The management of epilepsy in clinical practice: Do the needs manifested by the patients correspond to the priorities of the caring physicians? Findings from the EPINEEDS Study

Author: Giorgia Giussani, Gabriele Enia, Elisa Bianchi, Oriano Mecarelli, Ettore Beghi, Patrizia Pulitano, Claudia Cagnetti, Sara Baldinelli, Simona Lattanzi, Angela La Neve, Maria Tappatà, Teresa Francavilla, Giovanni De Maria, Vito Sofia, Loretta Giuliano, Greta Mainieri, Daniela Fatuzzo, Vincenzo Belcastro, Maurizio Elia, Giuseppe D'Orsi, Alessandra Lalla, Andrea Salmaggi, Francesco Brigo, Adriana Magaudda, Francesco Pisani, Santi Galletta, Laura R. Pisani, Massimo Raffaele, Domenico Cosenza, Flavio S. Villani, Rui M.M. Quintas, Rosa Cervellione, Simona Borroni, Stefano Meletti, Carlo Ferrarese, Giuseppina Barbella, Jacopo Di Francesco, Graziella Bogliun, Simone Beretta, Carlo A. Galimberti, Teresa A. Cantisani, Michela Cecconi, Maria G. Celani, Rossella Papetti, Filippo S. Giorgi, Umberto Aguglia, Sara Gasparini, Edoardo Ferlazzo, Paolo Manganotti, Giovanni Crichiutti, Giulia Bravar, Giussani, G., Enia, G., Bianchi, E., Mecarelli, O., Beghi, E., Pulitano, P., Cagnetti, C., Baldinelli, S., La Neve, A., Tappata, M., Francavilla, T., De Maria, G., Sofia, V., Giuliano, L., Mainieri, G., Fatuzzo, D., Belcastro, V., Elia, M., D'Orsi, G., Lalla, A., Salmaggi, A., Brigo, F., Magaudda, A., Pisani, F., Galletta, S., Pisani, L. R., Raffaele, M., Cosenza, D., Villani, F. S., Quintas, R. M. M., Cervellione, R., Borroni, S., Meletti, S., Ferrarese, C., Barbella, G., Di Francesco, J., Bogliun, G., Beretta, S., Galimberti, C. A., Cantisani, T. A., Cecconi, M., Celani, M. G., Papetti, R., Giorgi, F. S., Aguglia, U., Gasparini, S., Ferlazzo, E., Manganotti, P., Crichiutti, G., Bravar, G., Giussani, G, Enia, G, Bianchi, E, Mecarelli, O, Beghi, E, Pulitano, P, Cagnetti, C, Baldinelli, S, La Neve, A, Tappata, M, Francavilla, T, De Maria, G, Sofia, V, Giuliano, L, Mainieri, G, Fatuzzo, D, Belcastro, V, Elia, M, D'Orsi, G, Lalla, A, Salmaggi, A, Brigo, F, Magaudda, A, Pisani, F, Galletta, S, Pisani, L, Raffaele, M, Cosenza, D, Villani, F, Quintas, R, Cervellione, R, Borroni, S, Meletti, S, Ferrarese, C, Barbella, G, Di Francesco, J, Bogliun, G, Beretta, S, Galimberti, C, Cantisani, T, Cecconi, M, Celani, M, Papetti, R, Giorgi, F, Aguglia, U, Gasparini, S, Ferlazzo, E, Manganotti, P, Crichiutti, G, and Bravar, G
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Activities of daily living, Adolescent, Patients, Concordance, Satisfaction, Need, Disease, 03 medical and health sciences, Behavioral Neuroscience, Psychiatric comorbidity, Epilepsy, Young Adult, 0302 clinical medicine, Genetic etiology, Seizures, Physicians, Surveys and Questionnaires, Medicine, Humans, Epilepsy Needs, 030212 general & internal medicine, Aged, Aged, 80 and over, Health Services Needs and Demand, Physician-Patient Relations, business.industry, Prioritie, Communication, Needs, Priorities, Disease Management, Middle Aged, medicine.disease, Clinical Practice, Cross-Sectional Studies, Neurology, Italy, Socioeconomic Factors, Etiology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Purpose The purpose of this study was to assess the priorities of patients with epilepsy and caring physicians and the correspondence between these priorities. Methods In this multicenter cross-sectional study, patients with epilepsy attending 21 Italian epilepsy centers and their caring physicians filled anonymously questionnaires on the needs and priorities in the management of the disease. Included were questions on patients' demographics, diagnosis, treatment, and outcome of epilepsy. The concordance between patients and their physicians was assessed on various aspects of the diagnosis and care of the disease. Patients' satisfaction with communication, services, and patient–doctor relationship was also assessed. Results Included were 432 women and 355 men aged 15 to 88 years (median: 41 years). Disease duration ranged from 6 months to 75 years. A structural/metabolic etiology predominated (52.7%), followed by a (presumed) genetic etiology (33.0%). Seizure remission was present in 56.5% of cases. Comorbidities requiring chronic treatment were present in 27.5%, and comorbidities affecting self-sufficiency in 9.5%. Psychiatric comorbidity was present in 35.0%. Patients' priorities included discovery of the cause (89.1%), use of right drug (98.7%), use of a drug without chronic side effects (94.0%), and a life without restrictions (90.4%). Physicians' priorities included choice of right drug (83.5%) and use of drugs without chronic side effects (86.8%). Priorities varied with patients' age, sex, education, and occupation. Patient–doctor relationships were at least good in most cases. The information imparted was considered unsatisfactory by 21–44% of cases on seizure circumstances and complications, side effects of drugs, limitations of daily activities, and management of physiologic or pathologic conditions. Patients declared overall satisfaction, except for appointments (21.5%) and emergencies (30.8%). Conclusion Patients and physicians' priorities in the management of epilepsy overlap only in part. Patients are satisfied with their caring physicians and less satisfied with communication and management of routine and emergency problems.
Published: 2020

13. COVID-19 Pneumonia and ROX index: Time to set a new threshold for patients admitted outside the ICU

Author: Gustavo Olaizola, Mauro Castro Sayat, Nicolás Colaianni, Greta Spoladore, Stefano Nava, Irene Prediletto, Roberto Dongilli, Maria Laura Vega, Lara Pisani, Micaela Romagnoli, Guillermo Montiel, Vega M.L., Dongilli R., Olaizola G., Colaianni N., Sayat M.C., Pisani L., Romagnoli M., Spoladore G., Prediletto I., Montiel G., and Nava S.
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Respiratory rate, medicine.medical_treatment, Brief Communication, medicine.disease_cause, HFNC, law.invention, Diseases of the respiratory system, 03 medical and health sciences, ROX index, 0302 clinical medicine, Respiratory Rate, AHRF, law, Fraction of inspired oxygen, Non invasive respiratory support, Intubation, Intratracheal, medicine, Humans, Intubation, Oximetry, 030212 general & internal medicine, Acute hypoxemic respiratory failure, Survival analysis, Retrospective Studies, Mechanical ventilation, Noninvasive Ventilation, RC705-779, medicine.diagnostic_test, SARS-CoV-2, business.industry, Oxygen Inhalation Therapy, COVID-19, Intensive care unit, High flow nasal cannula, Intensive Care Units, Pulse oximetry, 030228 respiratory system, Emergency medicine, Respiratory Insufficiency, business, Nasal cannula
Abstract: High flow nasal cannula (HFNC) is used to treat acute hypoxemic respiratory failure (AHRF) even outside the ICU and the ROX index (pulse oximetry/fraction of inspired oxygen/respiratory rate) may predict HFNC failure. OBJECTIVE: The purpose of this investigation was therefore to verify whether the ROX index is an accurate predictor of HFNC failure for COVID-19 patients treated outside the intensive care unit (ICU) and to evaluate the validity of the previously suggested threshold. DESIGN: Multicenter study. Retrospective observational analysis of prospectively collected data. SETTING: 3 centres specialized in non-invasive respiratory support (Buenos Aires, Argentina; Bolzano and Treviso, Italy). Patients treated outside the ICU were analysed MEASUREMENTS: The variables to calculate the ROX index were collected during the first day of therapy at 2, 6, 12 and 24 hours and then recorded every 24 hours. HFNC failure was defined as escalation of respiratory support to invasive mechanical ventilation (IMV) or death. MAIN RESULTS: A total of 35 (29%) patients failed HFNC and required intubation. ROC analysis identified the 12-hour ROX index as the best predictor of intubation with an AUC of 0.7916[CI 95% 0.6905-0.8927] and the best threshold to be 5.99[Specificity 96% Sensitivity 62%]. In the survival analysis, a ROX value
Published: 2022
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14. Spheres derived from lung adenocarcinoma pleural effusions: molecular characterization and tumor engraftment

Author: Claudio Andreetti, Giuseppe Viglietto, Enrico Giarnieri, Claudia De Vitis, Luigi Ruco, Giuseppe Mesiti, Emanuele Marra, Gennaro Ciliberto, Erino A. Rendina, Rita Mancini, Carmelo Laudanna, Arianna Di Napoli, Donatella Malanga, Pasquale De Luca, Maria Rosaria Giovagnoli, Giuseppe Roscilli, Alberto Ricci, Pietro Zoppoli, Andrea Affuso, Alessia Noto, Luigi Aurisicchio, Salvatore Mariotta, Lara Pisani, Mancini R., Giarnieri E., de Vitis C., Malanga D., Roscilli G., Noto A., Marra E., Laudanna C., Zoppoli P., de Luca P., Affuso A., Ruco L., Di Napoli A., Mesiti G., Aurisicchio L., Ricci A., Mariotta S., Pisani L., Andreetti C., Viglietto G., Rendina E.A., Giovagnoli M.R., Ciliberto G., Mancini, R, Giarnieri, E, De Vitis, C, Malanga, D, Roscilli, G, Noto, A, Marra, E, Laudanna, C, Zoppoli, P, De Luca, P, Affuso, A, Ruco, L, Di Napoli, A, Mesiti, G, Aurisicchio, L, Ricci, A, Mariotta, S, Pisani, L, Andreetti, C, Viglietto, G, Rendina, Ea, Giovagnoli, Mr, and Ciliberto, G.
Subjects: Male, Pathology, Lung Neoplasms, Mouse, Pulmonology, Pleural effusion, Tumor Physiology, lcsh:Medicine, Cell Separation, Mice, SCID, Lung and Intrathoracic Tumors, Mice, Immunophenotyping, Molecular Cell Biology, Basic Cancer Research, Tumor Cells, Cultured, lcsh:Science, Aged, 80 and over, Multidisciplinary, Adenocarcinoma of the Lung, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Animal Models, Middle Aged, Immunohistochemistry, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, Neoplastic Stem Cells, Medicine, Adenocarcinoma, Female, Cellular Types, Research Article, Human, medicine.medical_specialty, Adenocarcinoma of Lung, Biology, Model Organisms, Diagnostic Medicine, Cancer stem cell, Spheroids, Cellular, Biomarkers, Tumor, Cell Adhesion, Adenocarcinoma of the lung, medicine, Animals, Humans, Lung cancer, Aged, Lung, Animal, lcsh:R, Cancers and Neoplasms, Computational Biology, Aldehyde Dehydrogenase, medicine.disease, Xenograft Model Antitumor Assays, Pleural Effusion, Malignant, Lung Neoplasm, Cancer cell, lcsh:Q, Neoplastic Stem Cell, Biomarkers, General Pathology, Genes, Neoplasm
Abstract: Malignant pleural effusions (MPEs) could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells. © 2011 Mancini et al.
Published: 2011

15. Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications

Author: Giulia Amore, Luca Vizioli, Luca Fasano, Caterina Tonon, Rita Rinaldi, Manuela Contin, Maria Teresa Dotti, Elisa Boschetti, Valentina Papa, Mauro Scarpelli, Alessia Pugliese, Susan Mohamed, Matteo Cescon, Roberto De Giorgio, Antonio Daniele Pinna, Leonardo Caporali, Lara Pisani, Massimiliano Filosto, Laura Ludovica Gramegna, Raffaele Lodi, Mariantonietta Capristo, Carlo Casali, Giovanna Cenacchi, Loris Pironi, Valerio Carelli, Maria Cristina Morelli, Francesco Sicurelli, Roberto D'Angelo, Roberta Costa, D'Angelo R., Boschetti E., Amore G., Costa R., Pugliese A., Caporali L., Gramegna L.L., Papa V., Vizioli L., Capristo M., Contin M., Mohamed S., Cenacchi G., Lodi R., Morelli M.C., Fasano L., Pisani L., Cescon M., Tonon C., Pinna A.D., Dotti M.T., Sicurelli F., Scarpelli M., Filosto M., Casali C., Pironi L., Carelli V., De Giorgio R., and Rinaldi R.
Subjects: Adult, medicine.medical_specialty, Neurology, medicine.medical_treatment, Hematopoietic stem cell transplantation, Liver transplantation, Gastroenterology, Ophthalmoparesis, Leukoencephalopathy, 03 medical and health sciences, 0302 clinical medicine, Mitochondrial Encephalomyopathies, Internal medicine, medicine, Humans, 030212 general & internal medicine, Thymidine phosphorylase, Gastrointestinal dysmotility, Ophthalmoplegia, business.industry, medicine.disease, Allogenic hematopoietic stem cell transplantation, Mitochondrial neurogastrointestinal encephalomyopathy, Neurology (clinical), medicine.symptom, business, Nucleoside, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.
Published: 2020
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16. Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Author: Pisani, Luigi, Algera, Anna Geke, Neto, Ary Serpa, Azevedo, Luciano, Pham, Tài, Paulus, Frederique, de Abreu, Marcelo Gama, Pelosi, Paolo, Dondorp, Arjen M, Bellani, Giacomo, Laffey, John G, Schultz, Marcus J, Martinez, Amadeu, Leal, Livia, Jorge Pereira, Antonio, de Oliveira Maia, Marcelo, Neto, Josè Aires, Piras, Claudio, Caser, Eliana Bernadete, Moreira, Cora Lavigne, Braga Gusman, Pablo, Dalcomune, Dyanne Moysés, Ribeiro de Carvalho, Alexandre Guilherme, Gondim, Louise Aline Romão, Castelo Branco Reis, Lívia Mariane, da Cunha Ribeiro, Daniel, de Assis Simões, Leonardo, Campos, Rafaela Siqueira, Fernandez Versiani dos Anjos, José Carlos, Bruzzi Carvalho, Frederico, Alves, Rossine Ambrosio, Nunes, Lilian Batista, Réa-Neto, Álvaro, de Oliveira, Mirella Cristine, Tannous, Luana, Cardoso Gomes, Brenno, Rodriguez, Fernando Borges, Abelha, Priscila, Lugarinho, Marcelo E, Japiassu, Andre, de Melo, Hélder Konrad, Lopes, Elton Afonso, Varaschin, Pedro, de Souza Dantas, Vicente Cés, Freitas Knibel, Marcos, Ponte, Micheli, de Azambuja Rodrigues, Pedro Mendes, Costa Filho, Rubens Carmo, Saddy, Felipe, Wanderley Castellões, Théia Forny, Silva, Suzana Alves, Osorio, Luiz Antonio Gomes, Mannarino, Dora, Espinoza, Rodolfo, Righy, Cassia, Soares, Marcio, Salluh, Jorge, Tanaka, Lilian, Aragão, Daniel, Tavares, Maria Eduarda, Kehdi, Maura Goncalves Pereira, Rezende, Valéria Maria Campos, Carbonell, Roberto Carlos Cruz, Teixeira, Cassiano, de Oliveira, Roselaine Pinheiro, Maccari, Juçara Gasparetto, Castro, Priscylla Souza, Berto, Paula, Schwarz, Patricia, Torelly, André Peretti, Lisboa, Thiago, Moraes, Edison, Dal-Pizzol, Felipe, Tomasi Damiani, Cristiane, Ritter, Cristiane, Ferreira, Juliana Carvalho, Teixeira Costa, Ramon, Caruso, Pedro, Amendola, Cristina Prata, de Oliveira, Amanda Maria R R, Silva, Ulysses V A, Sanches, Luciana Coelho, Almeida, Rosana D S, Azevedo, Luciano Cesar, Park, Marcelo, Schettino, Guilherme, Assunção, Murillo Santucci, Silva, Eliezer, Barboza, Carlos Eduardo, Junior, Antonio Paulo Nassar, Marzocchi Tierno, Paulo Fernando G M, Malbouisson, Luis Marcelo, Oliveira, Lucas, Cristovao, Davi, Neto, Manoel Leitão, Rego, Ênio, Fernandes, Fernanda Eugênia, Romano, Marcelo Luz Pereira, Cavalcanti, Alexandre Biasi, de Souza Barros, Dalton, Suzumura, Érica Aranha, Meira, Karla Loureiro, de Oliveira, Gustavo Affonso, Luciano, Paula Menezes, Pacheco, Evelin Drociunas, Mazza, Bruno Franco, Machado, Flavia Ribeiro, Ferreira, Elaine, dos Santos, Ronaldo Batista, Colombo, Alexandra Siqueira, Nogueira, Antonio Carlos, Fernandes, Juliana Baroni, Nóbrega, Raquel Siqueira, do CS Martins, Barbara, Soriano, Francisco, Morsch, Rafaela Deczka, Nunes, Andre Luiz Baptiston, de Almeida, Juliano Pinheiro, Hajjar, Ludhmila, Moulin, Sílvia, Giannini, Fábio Poianas, Baptiston Nunes, Andre Luiz, Rios, Fernando, Van Haren, Frank, Sottiaux, T, Lora, Fredy S, Azevedo, Luciano C, Depuydt, P, Fan, Eddy, Bugedo, Guillermo, Qiu, Haibo, Gonzalez, Marcos, Silesky, Juan, Cerny, Vladimir, Nielsen, Jonas, Jibaja, Manuel, Wrigge, Hermann, Matamis, Dimitrios, Ranero, Jorge Luis, Hashemian, S M, Amin, Pravin, Clarkson, Kevin, Kurahashi, Kiyoyasu, Villagomez, Asisclo, Zeggwagh, Amine Ali, Heunks, Leo M, Laake, Jon Henrik, Palo, Jose Emmanuel, do Vale Fernandes, Antero, Sandesc, Dorel, Arabi, Yaasen, Bumbasierevic, Vesna, Lorente, Jose A, Larsson, Anders, Piquilloud, Lise, Abroug, Fekri, McAuley, Daniel F, McNamee, Lia, Hurtado, Javier, Bajwa, Ed, Démpaire, Gabriel, Francois, Guy M, Sula, Hektor, Nunci, Lordian, Cani, Alma, Zazu, Alan, Dellera, Christian, Insaurralde, Carolina S, Alejandro, Risso V, Daldin, Julio, Vinzio, Mauricio, Fernandez, Ruben O, Cardonnet, Luis P, Bettini, Lisandro R, Bisso, Mariano Carboni, Osman, Emilio M, Setten, Mariano G, Lovazzano, Pablo, Alvarez, Javier, Villar, Veronica, Milstein, Cesar, Pozo, Norberto C, Grubissich, Nicolas, Plotnikow, Gustavo A, Vasquez, Daniela N, Ilutovich, Santiago, Tiribelli, Norberto, Chena, Ariel, Pellegrini, Carlos A, Saenz, María G, Estenssoro, Elisa, Brizuela, Matias, Gianinetto, Hernan, Gomez, Pablo E, Cerrato, Valeria I, Bezzi, Marco G, Borello, Silvina A, Loiacono, Flavia A, Fernandez, Adriana M, Knowles, Serena, Reynolds, Claire, Inskip, Deborah M, Miller, Jennene J, Kong, Jing, Whitehead, Christina, Bihari, Shailesh, Seven, Aylin, Krstevski, Amanda, Rodgers, Helen J, Millar, Rebecca T, Mckenna, Toni E, Bailey, Irene M, Hanlon, Gabrielle C, Aneman, Anders, Lynch, Joan M, Azad, Raman, Neal, John, Woods, Paul W, Roberts, Brigit L, Kol, Mark R, Wong, Helen S, Riss, Katharina C, Staudinger, Thomas, Wittebole, Xavier, Berghe, Caroline, Bulpa, Pierre A, Dive, Alain M, Verstraete, Rik, Lebbinck, Herve, Depuydt, Pieter, Vermassen, Joris, Meersseman, Philippe, Ceunen, Helga, Rosa, Jonas I, Beraldo, Daniel O, Ampinelli, Adenilton M R, Nassar Jr, Antonio P, Mataloun, Sergio, Moock, Marcelo, Thompson, Marlus M, Gonçalves, Claudio H, Antônio, Ana Carolina P, Ascoli, Aline, Biondi, Rodrigo S, Fontenele, Danielle C, Nobrega, Danielle, Sales, Vanessa M, Shindhe, Suresh, Ismail, Dk Maizatul Aiman B Pg Hj, Laffey, John, Beloncle, Francois, Davies, Kyle G, Cirone, Rob, Manoharan, Venika, Ismail, Mehvish, Goligher, Ewan C, Jassal, Mandeep, Nishikawa, Erin, Javeed, Areej, Curley, Gerard, Rittayamai, Nuttapol, Parotto, Matteo, Ferguson, Niall D, Mehta, Sangeeta, Knoll, Jenny, Pronovost, Antoine, Canestrini, Sergio, Bruhn, Alejandro R, Garcia, Patricio H, Aliaga, Felipe A, Farías, Pamela A, Yumha, Jacob S, Ortiz, Claudia A, Salas, Javier E, Saez, Alejandro A, Vega, Luis D, Labarca, Eduardo F, Martinez, Felipe T, Carreño, Nicolás G, Lora, Pilar, Liu, Haitao, Liu, Ling, Tang, Rui, Luo, Xiaoming, An, Youzhong, Zhao, Huiying, Gao, Yan, Zhai, Zhe, Ye, Zheng L, Wang, Wei, Li, Wenwen, Li, Qingdong, Zheng, Ruiqiang, Yu, Wenkui, Shen, Juanhong, Li, Xinyu, Yu, Tao, Lu, Weihua, Wu, Ya Q, Huang, Xiao B, He, Zhenyang, Lu, Yuanhua, Han, Hui, Zhang, Fan, Sun, Renhua, Wang, Hua X, Qin, Shu H, Zhu, Bao H, Zhao, Jun, Liu, Jian, Li, Bin, Liu, Jing L, Zhou, Fa C, Li, Qiong J, Zhang, Xing Y, Li-Xin, Zhou, Xin-Hua, Qiang, Jiang, Liangyan, Gao, Yuan N, Zhao, Xian Y, Li, Yuan Y, Li, Xiao L, Wang, Chunting, Yao, Qingchun, Yu, Rongguo, Chen, Kai, Shao, Huanzhang, Qin, Bingyu, Huang, Qing Q, Zhu, Wei H, Hang, Ai Y, Hua, Ma X, Li, Yimin, Xu, Yonghao, Di, Yu D, Ling, Long L, Qin, Tie H, Wang, Shou H, Qin, Junping, Han, Yi, Zhou, Suming, Vargas, Monica P, Silesky Jimenez, Juan I, González Rojas, Manuel A, Solis-Quesada, Jaime E, Ramirez-Alfaro, Christian M, Máca, Jan, Sklienka, Peter, Gjedsted, Jakob, Christiansen, Aage, Villamagua, Boris G, Llano, Miguel, Burtin, Philippe, Buzancais, Gautier, Beuret, Pascal, Pelletier, Nicolas, Mortaza, Satar, Mercat, Alain, Chelly, Jonathan, Jochmans, Sébastien, Terzi, Nicolas, Daubin, Cédric, Carteaux, Guillaume, de Prost, Nicolas, Chiche, Jean-Daniel, Daviaud, Fabrice, Pham, Tai, Fartoukh, Muriel, Barberet, Guillaume, Biehler, Jerome, Dellamonica, Jean, Doyen, Denis, Arnal, Jean-Michel, Briquet, Anais, Hraiech, Sami, Papazian, Laurent, Follin, Arnaud, Roux, Damien, Messika, Jonathan, Kalaitzis, Evangelos, Dangers, Laurence, Combes, Alain, Au, Siu-Ming, Béduneau, Gaetan, Carpentier, Dorothée, Zogheib, Elie H, Dupont, Herve, Ricome, Sylvie, Santoli, Francesco L, Besset, Sebastien L, Michel, Philippe, Gelée, Bruno, Danin, Pierre-Eric, Goubaux, Bernard, Crova, Philippe J, Phan, Nga T, Berkelmans, Frantz, Badie, Julio C, Tapponnier, Romain, Gally, Josette, Khebbeb, Samy, Herbrecht, Jean-Etienne, Schneider, Francis, Declercq, Pierre-Louis M, Rigaud, Jean-Philippe, Duranteau, Jacques, Harrois, Anatole, Chabanne, Russell, Marin, Julien, Bigot, Charlene, Thibault, Sandrine, Ghazi, Mohammed, Boukhazna, Messabi, Ould Zein, Salem, Richecoeur, Jack R, Combaux, Daniele M, Grelon, Fabien, Le Moal, Charlene, Sauvadet, Elise P, Robine, Adrien, Lemiale, Virginie, Reuter, Danielle, Dres, Martin, Demoule, Alexandre, Goldgran-Toledano, 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Mark J, Hormis, Anil P, Kannan, Santhana G, Namih, Miriam, Reschreiter, Henrik, Camsooksai, Julie, Kumar, Alek, Rugonfalvi, Szabolcs, Nutt, Christopher, Oneill, Orla, Seasman, Colette, Dempsey, Ged, Scott, Christopher J, Ellis, Helen E, Mckechnie, Stuart, Hutton, Paula J, Di Tomasso, Nora N, Vitale, Michela N, Griffin, Ruth O, Dean, Michael N, Cranshaw, Julius H, Willett, Emma L, Ioannou, Nicholas, Gillis, Sarah, Csabi, Peter, Macfadyen, Rosaleen, Dawson, Heidi, Preez, Pieter D, Williams, Alexandra J, Boyd, Owen, De Gordoa, Laura Ortiz-Ruiz, Bramall, Jon, Symmonds, Sophie, Chau, Simon K, Wenham, Tim, Szakmany, Tamas, Toth-Tarsoly, Piroska, Mccalman, Katie H, Alexander, Peter, Stephenson, Lorraine, Collyer, Thomas, Chapman, Rhiannon, Cooper, Raphael, Allan, Russell M, Sim, Malcolm, Wrathall, David W, Irvine, Donald A, Zantua, Kim S, Adams, John C, Burtenshaw, Andrew J, Sellors, Gareth P, Welters, Ingeborg D, Williams, Karen E, Hessell, Robert J, Oldroyd, Matthew G, Battle, Ceri E, 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Nicholas M, Judy, Claine, Saito, Shigeki, Kheir, Fayez M, Schlichting, Adam B, Delsing, Angela, Elmasri, Mary, Crouch, Daniel R, Ismail, Dina, Blakeman, Thomas C, Dreyer, Kyle R, Baron, Rebecca M, Grijalba, Carolina Quintana, Hou, Peter C, Seethala, Raghu, Aisiku, Imo, Henderson, Galen, Frendl, Gyorgy, Hou, Sen-Kuang, Owens, Robert L, Schomer, Ashley, Bumbasirevic, Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Rodgers, Helen, Dixon, Barry, Smith, Roger, Kol, Mark, Wong, Helen, Schmid, Werner, Hermans, Greet, Bourgeois, Marc, Anquez, Nathalie, Decruyenaere, Johan, DeCrop, Luc, Souza dos Santos, Rafaella, Beraldo, Daniel, dos Santos, Moreno Calcagnotto, Pellegrini, Jose Augusto Santos, Oliveira, Vanessa, Munhoz, Carlos, Peçanha, Ana Carolina, da Silva Ramos, Fernando José, Maia, Israel, Bahl, Marina, Biondi, Rodrigo, Prado, Daniel, Pinto, Sérgio Felix, Salgado, Jean, Falcão, Luis Fernando, Macruz, Tiago, Ruas, Kessia, Mecatti, Giovana Colozza, Caser, Eliane Bernadete, Gava, 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Vesna, Jovanovic, Bojan, Surbatovic, Maja, Veljovic, Milic, Rodgers, Helen, Dixon, Barry, Smith, Roger, Kol, Mark, Wong, Helen, Schmid, Werner, Hermans, Greet, Bourgeois, Marc, Anquez, Nathalie, Decruyenaere, Johan, DeCrop, Luc, Souza dos Santos, Rafaella, Beraldo, Daniel, dos Santos, Moreno Calcagnotto, Pellegrini, Jose Augusto Santo, Oliveira, Vanessa, Munhoz, Carlo, Peçanha, Ana Carolina, da Silva Ramos, Fernando José, Maia, Israel, Bahl, Marina, Biondi, Rodrigo, Prado, Daniel, Pinto, Sérgio Felix, Salgado, Jean, Falcão, Luis Fernando, Macruz, Tiago, Ruas, Kessia, Mecatti, Giovana Colozza, Caser, Eliane Bernadete, Gava, Isabela Ambrósio, Carreño, Nicolá, Morales, Mauricio, Avendaño, Rossana, Aguirre, Stefania, Sribar, Andrej, Klaric, Vlasta, Skilijic, Sonja, Dvorscak, Matea Bogdanovic, Krkusek, Marijana, Jurjevic, Matija, Karanovic, Nenad, Simurina, Tatjana, Stourac, Petr, Kratochvil, Milan, Schlegel, Christian, Treschan, Tanja A, Schaefer, Maximilian, Aytulun, Akut, Kienbaum, Peter, Jaafar, Rola, Collins, Daniel, Plant, Robert, Melchionda, Giuseppe, Di Lauro, Eduardo, Russotto, Vincenzo, Caione, Raffaele, Mestria, Donatella, Volta, Carlo Alberto, Seghelini, Elisa, Sales, Gabriele, D'Antini, Davide, Severgnini, Paolo, Bacuzzi, Alessandro, Peluso, Lorenzo, Verrastro, Pasquale, Raimondo, Pasquale, Gecaj-Gashi, Agreta, Tuinman, Pieter Roel, Alberts, Erna, van den Hul, Ingrid, Kuiper, Michael, de Wilde, Robert BP, Koopmans, Matty, Kose, Isil, Zincircioglu, Çiler, Dogan, Nazim, Aydin, Demet, Denker, Ahmet Sukru, Buyukkocak, Unase, Akgun, Nur, Turan, Güldem, Senturk, Evren, Demirtürk, Zerrin, Özcan, Perihan Ergin, Ekinci, Osman, Saylan, Sedat, Eren, Gulay, Ulger, Fatma, Dilek, Ahmet, Ulusoy, Hulya, Goktas, Ugur, Soyoral, Lokman, Toman, Huseyin, Orak, Yavuz, Kahveci, Feda, Mills, Gary H, Pinder, Angela, Walker, Rachel, Harrison, Jonathan, Snell, Jane, Pearson, Rachel, Sharman, Michael, Kaloo, Claire, Bynorth, Natalie, Matthews, Kelly, Hughes, Chloe, Rose, Alastair, Simeson, Karen, Niska, Lotta, Huneke, Nathan, Adderly, Jane, Padilla-Harris, Cheryl, Oliver, Rebecca, Brohi, Farooq, Wilson, Natalie, Talbot, Helen, Wilson, Deborah, Smith, Deborah, Dark, Paulo, Evans, Tracey, Fisher, Nicola, Montgomery, Jane, Fitzell, Pauline, Muench, Christoph, Hugill, Keith, Cirstea, Emanuel, Bentley, Andrew, Lynch, Katie, White, Ian, Cooper, Jonathan, Brazier, Melinda, Devile, Michael, Parris, Michael, Gill, Pardeep, Patel, Tasmin, Criswell, John, Trodd, Dawn, Griffin, Denise, Martin, Jane, Wreybrown, Caroline, Bewley, Jeremy, Sweet, Katie, Grimmer, Lisa, Kozlowski, Marta, James, Shanaz, Limb, Jame, Cowton, Amanda, Rogerson, David, Downes, Charlotte, Melbourne, Susan, Humphries, Ryan, Pulletz, Mark, Moreton, Sarah, Janes, Stephanie, Corner, Andrew, Linnett, Vanessa, Ritzema, Jenny, Watters, Malcolm, Windebank, Steve, Chenna, Shailaja, Howard-Griffin, Richard, Turner, Kate, Suresh, Sheeba, Blaylock, Heather, Bell, Stephanie, Blenk, Karl, Everett, Lynn, Hadfield, Daniel, Harris, Clair, Chan, Alexandre, Birch, Sian, Pegg, Claire, Plowright, Catherine, Cooper, Lucy, Hatton, Tom, McCullagh, Iain, Wright, Stephen, Scott, Carmen, Boyd, Christine, Holliday, Mark, Poultney, Una, Crowther, Hannah, Thornthwaite, Sarah, Hollister, Nigel, Hunt, Jane, Skinner, Amanda, Matsa, Ramprasad, Salt, Ruth, Matthews, Claire, Venner, Nicola, Barcraft-Barnes, Helena, Tbaily, Lee, Pogson, David, Mouland, Johanna, Rose, Steve, Lamb, Nicola, Tarmey, Nichola, Knighton, John, Giles, Julian, Weller, Debbie, Reed, Isabelle, Hormis, Anil, Pearson, Sallyane, Harris, Meredith, Howe, Joanne, Paddle, Jonathan, Burt, Karen, Welters, Ingeborg, Walker, Anna, Youds, Laura, Hendry, Sam, Shaw, David, Williams, Karen, Hollands, Robin, Carnahan, Mandy, Stickley, Johanna, Miller, Claire, Donaldson, Denise, Tonks, Louise, Creagh-Brown, Ben, Hull, Daniel, Ortiz-Ruiz, Laura, Gopal, Shammer, Metherell, Stella, Spencer, Hazel, Frey, Christian, Brown, Carly, Clifford, Gayle, Leaver, Susannah, Ryan, Christine, Mellinghoff, Johannes Mellinghoff, Prudden, Sarah Prudden, Green, Helen Green, Roy, Alistair Roy, Furneval, Julie Furneval, Bell, Adam Bell, Lakhani, Sandeep Lakhani, Fasting, Lousie Fasting, Murray, Lorna Murray, Preller, Kobu, McInerney, Amy, Beavis, Sarah, Whileman, Amanda, Toms, Julie, Glenn, Sue, Ramali, Mohamed, Ghosh, Alison, Bullock, Clare, Barrell, Lisa, Young, Eoin, Robertson, Helen, Faulkner, Maria, MacNaughton, Peter, Tyson, Susan, Pulak, Paul, Sewell, Terri-Ann, Smalley, Christopher, Jacob, Reni, Alzugaray, Pedro, Vidal Melo, Marcos F, Joyce, Kristen, Needleman, Joseph, Ahsan, Areef, Faiz, Abul, Alam, AKM Shamsul, Khatoon, Syeda Nafisa, Nath, Ranjan Kumer, Rahman Chowdhury, Mohammed Abdur, Banik, Debabrata, Mondol, Montosh Kumar, Bhuiyan, Sakibur Rahman, Nazneed, Suraiya, Sultana, Rozina, Hamid, Tarikul, Hossain, Mozaffer, Reza, Syed Tariq, Asaduzzaman, Muhammad, Salim, Mohammad, Mostafa Kamal, Abu Hena, Taher, Sheikh Mohammed, Taohid, Taohidul Majid, Karmaker, Pranab, Roy, Sabyasachi, Das, Shantanu, Sarkar, Sohel Ahmed, Dutta, Monju Lal, Roy, Poulomi, Iyer, Shivakumar, Krishna, Bhuvana, Sampath, Sriram, Pattnaik, Rajyabardhan, Kasi, Chinni Krishna, Shah, Jignesh, Dongre, Anand, Reza Hashemian, Seyed Mohammad, Nooraei, Navid, Raessi Estabragh, Reza, Malekmohammad, Majid, Khoundabi, Batoul, Mobasher, Maziar, Mohd Yunos, Nor'azim, Kassim, Mahazir, Voon, Chern Min, Das, Stanis Sutharsa, Azauddin, Siti Nur Suhaila, Dorasamy, Dharshinie, Tai, Li Ling, Mat Nor, Mohd Basri, Zarudin, Nurhafizah, Hasan, Mohd Shahnaz, Jamaluddin, Mohamad Fadhil Hadi, Othman Jailani, Mohamad Irfan, Kayashta, Gyan, Adhikari, Aaradhana, Pangeni, Raju, Hashmi, Madiha, Joseph, Sonia, Akhtar, Aftab, Qadeer, Aayesha, Memon, Iqbal, Ali, Syed Muneeb, Idrees, Farah, Kamal, Saima, Hanif, Sadaf, Rehman, Atta Ur, Taqi, Arshad, Hussain, Tanveer, Farooq, Ahmed, Khaskheli, Saleh, Hayat, Muhammad, Indraratna, Kanishka, Beane, Abigail, Haniffa, Rashan, Samaranayake, Upeka, Mathanalagan, Sathiyamoorthy, Gunaratne, Asoka, Mithraratne, Nimangee, Thilakasiri, Kaushila, Pilimatalawwe, Chamila, Dilhani, Y A Hasitha, Fernando, Marie, Ranatunge, Kumudini, Samarasinghe, Loranthi, Vaas, Manori, Edirisooriya, Manoj, Sigera, Chathurani, Arumoli, Janaki, De Silva, Kesharie, Kudavidanage, Bimal, Pinto, Visanthi, Dissanayake, Lakshman, Chittawatanarat, Kaweesak, Kongpolprom, Napplika, Silachamroon, Udomsak, Pornsuriyasak, Prapaporn, Petnak, Tananchai, Singhatas, Pongsasit, Tangsujaritvijit, Viratch, Rungruanghiranya, Suthat, Piriyapatsom, Annop, Juntaping, Kanokkarn, Trongtrakul, Konlawij, Thungtitigul, Poungrat, Tajarernmuang, Pattraporn, Chatmongkolchart, Sunisa, Bhurayanontachai, Rungsun, Akaraborworn, Osaree, Navasakulpong, Asma, Surasit, Karjbundid, Thwaites, Louise, Nadjm, Behzad, Vu Quoc, Dat, Nguyen Thi Thanh, Ha, Nguyen Van, Kinh, Duong Bich, Thuy, Lam Minh, Yen, Anesthesiology, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, Graduate School, Intensive Care Medicine, AII - Inflammatory diseases, Nursing, and ACS - Microcirculation
Subjects: Male, Sociodemographic Factors, Respiration, Artificial/methods, ARDS, mechanical ventilation, Severity of Illness Index, NO, Settore MED/41 - ANESTESIOLOGIA, 80 and over, Tidal Volume, Humans, Hospital Mortality, Prospective Studies, ddc:610, Developing Countries, Aged, Hospital Mortality/trends, Aged, 80 and over, Developed Countries/statistics & numerical data, Developing Countries/statistics & numerical data, Respiration, Developed Countries, Articles, General Medicine, acute respiratory distress syndrome, Length of Stay, Middle Aged, Respiration, Artificial, Intensive Care Units, Observational Studies as Topic, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Length of Stay/statistics & numerical data, Artificial, Intensive Care Units/statistics & numerical data, Income, Female
Abstract: Contains fulltext : 252214.pdf (Publisher’s version ) (Open Access) BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H(2)O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p
Published: 2022
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17. Early awake proning in critical and severe COVID-19 patients undergoing noninvasive respiratory support: A retrospective multicenter cohort study

Author: Luca Tabbì, Giulia Bruzzi, Enrico Clini, Linda Manicardi, Stefano Nava, Stefano Busani, Gabriele Corsi, Cristina Mussini, Irene Prediletto, Vittoria Comellini, Roberto D'Amico, Ilaria Bassi, Riccardo Fantini, Ivana Castaniere, Federico Tagariello, Massimo Girardis, Filippo Gozzi, Marco Carpano, Lara Pisani, Alessandro Marchioni, Roberto Tonelli, Dario Andrisani, Tonelli R., Pisani L., Tabbi L., Comellini V., Prediletto I., Fantini R., Marchioni A., Andrisani D., Gozzi F., Bruzzi G., Manicardi L., Busani S., Mussini C., Castaniere I., Bassi I., Carpano M., Tagariello F., Corsi G., d'Amico R., Girardis M., Nava S., and Clini E.
Subjects: Pulmonary and Respiratory Medicine, Coronavirus disease 2019 (COVID-19), ARF, acute respiratory failure, Vt, tidal volume, medicine.medical_treatment, RR, respiratory rate, Acute respiratory failure, NRS, non-invasive respiratory support, law.invention, Cohort Studies, 03 medical and health sciences, Prone position, 0302 clinical medicine, Randomized controlled trial, law, ICU, Intensive Care Unit, medicine, Humans, Intubation, 030212 general & internal medicine, Wakefulness, APACHE II, acute physiology and chronic health evaluation II score, HFNC, High Flow Nasal Cannulae, Retrospective Studies, COVID-19, Acute respiratory failure, Non-invasive mechanical ventilation, Prone position, NIV, non-invasive mechanical ventilation, business.industry, ETI, endotracheal intubation, CPAP, continuous positive airways pressure, Confounding, COVID-19, MV, mechanical ventilation, Retrospective cohort study, SAPS II, simplified acute physiology score, PSV, pressure support ventilation, HR, hazard ratio, SOFA, subsequent organ failure assessment, OR, odds ratio, 030228 respiratory system, PEEP, positive end expiratory pressure, Anesthesia, Breathing, Original Article, Non-invasive mechanical ventilation, Respiratory Insufficiency, business, Cohort study
Abstract: BACKGROUND/MATERIALS AND METHODS: This retrospective cohort study was conducted in two teaching hospitals over a 3-month period (March 2010-June 2020) comparing severe and critical COVID-19 patients admitted to Respiratory Intensive Care Unit for non-invasive respiratory support (NRS) and subjected to awake prone position (PP) with those receiving standard care (SC). Primary outcome was endotracheal intubation (ETI) rate. In-hospital mortality, time to ETI, tracheostomy, length of RICU and hospital stay served as secondary outcomes. Risk factors associated to ETI among PP patients were also investigated. RESULTS: A total of 114 patients were included, 76 in the SC and 38 in the PP group. Unadjusted Kaplan-Meier estimates showed greater effect of PP compared to SC on ETI rate (HRâ¯=â¯0.45 95% CI [0.2-0.9], pâ¯=â¯0.02) even after adjustment for baseline confounders (HRâ¯=â¯0.59 95% CI [0.3-0.94], pâ¯=â¯0.03). After stratification according to non-invasive respiratory support, PP showed greater significant benefit for those on High Flow Nasal Cannulae (HRâ¯=â¯0.34 95% CI [0.12-0.84], pâ¯=â¯0.04). Compared to SC, PP patients also showed a favorable difference in terms of days free from respiratory support, length of RICU and hospital stay while mortality and tracheostomy rate were not significantly different. CONCLUSIONS: Prone positioning in awake and spontaneously breathing Covid-19 patients is feasible and associated with a reduction of intubation rate, especially in those patients undergoing HFNC. Although our results are intriguing, further randomized controlled trials are needed to answer all the open questions remaining pending about the real efficacy of PP in this setting.
Published: 2022

18. Extracorporeal carbon dioxide removal for treatment of exacerbated chronic obstructive pulmonary disease (ORION): study protocol for a randomised controlled trial

Author: Maria Laura Vega, Claudia Filippini, Lara Pisani, Stefano Nava, Irene Cavalli, Tommaso Tonetti, Elisa Maietti, V. Marco Ranieri, Tonetti T., Pisani L., Cavalli I., Vega M.L., Maietti E., Filippini C., Nava S., and Ranieri V.M.
Subjects: medicine.medical_specialty, Medicine (General), Exacerbation, medicine.medical_treatment, Medicine (miscellaneous), law.invention, Hypercapnia, Study Protocol, Pulmonary Disease, Chronic Obstructive, R5-920, Randomized controlled trial, law, Intensive care, ECCO2R, medicine, COPD, Humans, Multicenter Studies as Topic, Pharmacology (medical), Intensive care medicine, Randomized Controlled Trials as Topic, Mechanical ventilation, Noninvasive Ventilation, business.industry, Extracorporeal CO2 removal, Carbon Dioxide, medicine.disease, Acute exacerbations of chronic obstructive pulmonary disease, Clinical trial, Respiratory acidosis, NIV, Breathing, Non-invasive ventilation, Quality of Life, business, Human
Abstract: Background Hypercapnic exacerbations are severe complications of chronic obstructive pulmonary disease (COPD), characterized by negative impact on prognosis, quality of life and healthcare costs. The present standard of care for acute exacerbations of COPD is non-invasive ventilation; when it fails, the use of invasive mechanical ventilation is inevitable, but is associated with extremely poor prognosis. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis, which inevitably leads to failure of non-invasive ventilation. Although the use of ECCO2R for acute exacerbations of COPD is steadily increasing, solid evidence on its efficacy and safety is scarce, thus the need for a randomized controlled trial. Methods multicenter randomized controlled unblinded clinical trial including 284 (142 per arm) patients with acute hypercapnic respiratory failure caused by exacerbation of COPD, requiring respiratory support with NIV. The primary outcome is event free survival at 28 days, a composite outcome defined by survival in absence of prolonged mechanical ventilation, severe hypoxemia, septic shock and second episode of COPD exacerbation. Secondary outcomes are incidence of endotracheal intubation and tracheostomy, intensive care and hospital length-of-stay and 90-day mortality. Discussion Acute exacerbations of COPD represent a significant burden in terms of prognosis, quality of life and healthcare costs. Lack definite evidence despite increasing use of ECCO2R justifies a randomized trial to evaluate whether patients with acute hypercapnic acidosis not responsive to NIV should undergo invasive mechanical ventilation (with all serious related risks) or be treated with ECCO2R to avoid invasive ventilation but be exposed to possible adverse events of ECCO2R. Owing to its pragmatic nature, sample size and composite primary outcome, this trial aims at providing valuable answers to relevant questions for clinical treatment of acute exacerbations of COPD. Trial registration ClinicalTrials.gov, NCT04582799. Registered 12 October 2020, .
Published: 2021

19. High flow through nasal cannula in exacerbated COPD patients: a systematic review

Author: Federico Longhini, Marinella Astuto, Lara Pisani, Irene Prediletto, Pisani L., Astuto M., Prediletto I., and Longhini F.
Subjects: Pulmonary and Respiratory Medicine, Chronic obstructive pulmonary disease, High flow nasal cannula, Hypercapnia, Non-invasive ventilation, Oxygen, Positive-pressure respiration, Respiratory insufficiency, Respiratory therapy, Exacerbation, medicine.medical_treatment, medicine.disease_cause, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Respiratory Rate, Oxygen therapy, medicine, Humans, 030212 general & internal medicine, Work of Breathing, lcsh:RC705-779, COPD, Noninvasive Ventilation, business.industry, lcsh:Diseases of the respiratory system, medicine.disease, Respiratory acidosis, Treatment Outcome, medicine.anatomical_structure, 030228 respiratory system, Anesthesia, Disease Progression, Acidosis, Respiratory, Blood Gas Analysis, medicine.symptom, business, Nasal cannula, Respiratory tract
Abstract: Chronic Obstructive Pulmonary Disease (COPD) history is characterized by episodes of exacerbation of varying severity, featured by acute worsening of respiratory symptoms, commonly precipitated by respiratory tract infection. The recent ERS/ATS clinical practice guidelines strongly recommend the application of non invasive ventilation (NIV) for patients with acute respiratory failure (ARF) leading to acute or acute-on-chronic respiratory acidosis (pH 7.35) and not for those patients with acute exacerbation of COPD (AECOPD) and hypercapnia who are not acidotic. In recent years, High-Flow through Nasal Cannula (HFNC) has been introduced in the clinical practice.We designed the present systematic review of the literature to assess all effects of HFNC use reported in exacerbated COPD patients. In this setting, HFNC is able to keep PaCO2 unmodified, while oxygenation slightly deteriorates as opposed to NIV. Furthermore, the work of breathing is reduced with HFNC by a similar extent to NIV, while it increases by 40–50% during conventional oxygen therapy (COT). HFNC is also reported to be more comfortable than COT and NIV. Despite these results, little and limited evidence for improved clinical outcomes is currently available. Keywords: Chronic obstructive pulmonary disease, Oxygen, High flow nasal cannula, Non-invasive ventilation, Respiratory therapy, Respiratory insufficiency, Hypercapnia, Positive-pressure respiration
Published: 2019
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20. COVID-19 pneumonia and ROX index: Time to set a new threshold for patients admitted outside the ICU. Authors' reply

Author: G Olaizola, M C Sayat, Micaela Romagnoli, Irene Prediletto, Nicolás Colaianni, Lara Pisani, Maria Laura Vega, Guillermo Montiel, Roberto Dongilli, Greta Spoladore, Stefano Nava, Vega M.L., Dongilli R., Olaizola G., Colaianni N., Sayat M.C., Pisani L., Romagnoli M., Spoladore G., Prediletto I., Montiel G., and Nava S.
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, medicine.medical_specialty, Noninvasive Ventilation, RC705-779, Coronavirus disease 2019 (COVID-19), business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Intensive Care Unit, COVID-19, medicine.disease, Oxygen, Diseases of the respiratory system, Pneumonia, Intensive Care Units, Respiratory Rate, Emergency medicine, Medicine, Humans, business, Letter to the Editor, Human
Published: 2021

21. Awake proning as an adjunctive therapy for refractory hypoxemia in non-intubated patients with COVID-19 acute respiratory failure: Guidance from an international group of healthcare workers

Author: Eva Åkerman, Luigi Pisani, Lieuwe D. J. Bos, Jean-Damien Ricard, Oriol Roca, Kathleen M. Vollman, Bairbre McNicholas, Laura A. Buiteman-Kruizinga, Jaques Sztajnbok, Antonio Artigas, Lisa M.N. Maduro, Paul Dark, Chiara Sartini, Weihua Lu, Rebecca Inglis, Vittorio Scaravilli, Mary Ellen Gilder, Diego De Mendoza, Frederique Paulus, Hendrik de Bruin, Eloi Prud'Homme, Peter E. Spronk, John G. Laffey, Alfred Papali, Gregg Chesney, Marcus J. Schultz, Margaretha C. E. van der Woude, Willemke Stilma, Luis Morales-Quinteros, Cindy S. Chu, Tobias Brummaier, Arjen M. Dondorp, Youssef Trigui, François Nosten, Chaisith Sivakorn, Harm J.H. Gijsbers, Domenico Luca Grieco, Gianluca Paternoster, Giovanni Landoni, Thomas J.C. Bosman, Francesco Carcò, Andrew Bentley, Rose McGready, Stilma, W., Akerman, E., Artigas, A., Bentley, A., Bos, L. D., Bosman, T. J. C., De Bruin, H., Brummaier, T., Buiteman-Kruizinga, L. A., Carco, F., Chesney, G., Chu, C., Dark, P., Dondorp, A. M., Gijsbers, H. J. H., Gilder, M. E., Grieco, D. L., Inglis, R., Laffey, J. G., Landoni, G., Lu, W., Maduro, L. M. N., Mcgready, R., Mcnicholas, B., De Mendoza, D., Morales-Quinteros, L., Nosten, F., Papali, A., Paternoster, G., Paulus, F., Pisani, L., Prud'Homme, E., Ricard, J. -D., Roca, O., Sartini, C., Scaravilli, V., Schultz, M. J., Sivakorn, C., Spronk, P. E., Sztajnbok, J., Trigui, Y., Vollman, K. M., Van Der Woude, M. C. E., Graduate School, Intensive Care Medicine, Nursing, Pulmonology, ACS - Heart failure & arrhythmias, AII - Infectious diseases, ACS - Pulmonary hypertension & thrombosis, ACS - Diabetes & metabolism, ACS - Microcirculation, Faculteit Gezondheid, Urban Vitality, Lectoraat Critical Care, and Pulmonary medicine
Subjects: medicine.medical_specialty, Supine position, Health Personnel, medicine.medical_treatment, 030231 tropical medicine, Hypoxemia, 03 medical and health sciences, Work of breathing, 0302 clinical medicine, Virology, Prone Position, medicine, Humans, Intubation, Wakefulness, Hypoxia, Intensive care medicine, Continuous Positive Airway Pressure, SARS-CoV-2, business.industry, COVID-19, Articles, medicine.disease, Pneumonia, Infectious Diseases, Acute Disease, Adjunctive treatment, Breathing, Parasitology, Observational study, medicine.symptom, Respiratory Insufficiency, business
Abstract: Non-intubated patients with acute respiratory failure due to COVID-19 could benefit from awake proning. Awake proning is an attractive intervention in settings with limited resources, as it comes with no additional costs. However, awake proning remains poorly used probably because of unfamiliarity and uncertainties regarding potential benefits and practical application. To summarize evidence for benefit and to develop a set of pragmatic recommendations for awake proning in patients with COVID-19 pneumonia, focusing on settings where resources are limited, international healthcare professionals from high and low- and middle-income countries (LMICs) with known expertise in awake proning were invited to contribute expert advice. A growing number of observational studies describe the effects of awake proning in patients with COVID-19 pneumonia in whom hypoxemia is refractory to simple measures of supplementary oxygen. Awake proning improves oxygenation in most patients, usually within minutes, and reduces dyspnea and work of breathing. The effects are maintained for up to 1 hour after turning back to supine, and mostly disappear after 6–12 hours. In available studies, awake proning was not associated with a reduction in the rate of intubation for invasive ventilation. Awake proning comes with little complications if properly implemented and monitored. Pragmatic recommendations including indications and contraindications were formulated and adjusted for resource-limited settings. Awake proning, an adjunctive treatment for hypoxemia refractory to supplemental oxygen, seems safe in non-intubated patients with COVID-19 acute respiratory failure. We provide pragmatic recommendations including indications and contraindications for the use of awake proning in LMICs.
Published: 2021
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22. Noninvasive Ventilation in Unplanned Endotracheal Extubation: Just a Little Help From My Friend?

Author: Stefano Nava, Irene Prediletto, Lara Pisani, Nava S., Prediletto I., and Pisani L.
Subjects: Pulmonary and Respiratory Medicine, Noninvasive Ventilation, business.industry, medicine.medical_treatment, MathematicsofComputing_GENERAL, General Medicine, Airway Extubation, Critical Care and Intensive Care Medicine, Respiration, Artificial, GeneralLiterature_MISCELLANEOUS, InformationSystems_GENERAL, 03 medical and health sciences, Endotracheal extubation, 0302 clinical medicine, 030228 respiratory system, Anesthesia, Intubation, Intratracheal, medicine, Humans, Intubation, Unplanned extubation, Noninvasive ventilation, business, Human
Abstract: Unplanned extubation is a rather common issue in the ICU. Surprisingly, as documented in this issue of the Journal by Kudela et al,[1][1] only a relatively small portion of subjects require re-intubation. This may mean that many individuals remain intubated longer than necessary. The main reasons
Published: 2019
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23. Maternal caesarean section infection (MACSI) in Sierra Leone: a case-control study

Author: Michael M. Koroma, F. Oliva, Annalisa Saracino, Claudia Marotta, Luigi Pisani, Francesca Tognon, G. Pellizer, Damiano Pizzol, Davide Fiore Bavaro, Nicola Veronese, Giovanni Putoto, S. Ponte, V. Lippolis, Vincenzo Pisani, P. Nanka Bruce, Laura Monno, F. Di Gennaro, Di Gennaro, F., Marotta, C., Pisani, L., Veronese, N., Pisani, V., Lippolis, V., Pellizer, G., Pizzol, D., Tognon, F., Bavaro, D.F., Oliva, F., Ponte, S., Nanka Bruce, P., Monno, L., Saracino, A., Koroma, M.M., Putoto, G., Intensive Care Medicine, Graduate School, AII - Infectious diseases, and ACS - Pulmonary hypertension & thrombosis
Subjects: Adult, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, Sierra leone, Sierra Leone, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, medicine, Humans, Surgical Wound Infection, Caesarean section, 030212 general & internal medicine, Prospective Studies, Original Paper, 030219 obstetrics & reproductive medicine, Obstetrics, business.industry, Cesarean Section, Incidence (epidemiology), Incidence, Case-control study, Antibiotic, Odds ratio, surgical site infection, medicine.disease, Survival Analysis, Confidence interval, Hospitals, Infectious Diseases, maternal death, Case-Control Studies, Maternal death, Female, business, Surgical site infection
Abstract: Sierra Leone is the country with highest maternal mortality and infections are the underlying cause in 11% of maternal deaths, but the real burden remains unknown. This study aims to determine the incidence and risk factors of surgical site infection (SSI) post-caesarean section (CS) in women admitted to Princess Christian Maternity Hospital (PCMH) in Freetown, Sierra Leone. A prospective case-control (1:3 ratio) study was implemented from 1 May 2018 to 30 April 2019 and 11 women presenting with suspected or confirmed infection post-CS were screened for inclusion as a case. For each case, three patients undergoing CS on the same day and admitted to the same ward, but not presenting with SSI, were selected as controls. The post-CS infection rate was 10.9%. Two hundred and fifty-four clinically confirmed cases were enrolled and matched with 762 control patients. By multivariable analysis, the risk factors for SSI were: being single (odds ratio (OR) 1.48, 95% confidence interval (CI) 1.36-1.66), low education level (OR 1.68, 95% CI 1.55-1.84), previous CS (OR 1.27, 95% CI 1.10-1.52), presenting with premature membranes rupture (OR 1.49, 95% CI 1.18-1.88), a long decision-incision time (OR 2.08, 95% CI 1.74-2.24) and a high missing post-CS antibiotic doses rate (OR 2.52, 95% CI 2.10-2.85). Copyright © The Author(s), 2020. Published by Cambridge University Press.
Published: 2020

24. Effects of high-flow nasal cannula in patients with persistent hypercapnia after an acute COPD exacerbation: a prospective pilot study

Author: Sara Betti, Carlotta Biglia, Vittoria Comellini, Irene Prediletto, Stefano Nava Fers, Luca Fasano, Letizia Bacchi-Reggiani, Lara Pisani, Vito Catalanotti, Pisani L., Betti S., Biglia C., Fasano L., Catalanotti V., Prediletto I., Comellini V., Bacchi-Reggiani L., and Fers S.N.
Subjects: Male, Pulmonary and Respiratory Medicine, Time Factors, Exacerbation, Pilot Projects, medicine.disease_cause, Catheterization, law.invention, Hypercapnia, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Humans, Medicine, In patient, Prospective Studies, 030212 general & internal medicine, Aged, Aged, 80 and over, lcsh:RC705-779, COPD, Noninvasive Ventilation, business.industry, Chronic obstructive pulmonary disease, Overlap syndrome, lcsh:Diseases of the respiratory system, Persistent hypercapnia, Carbon Dioxide, Long term non invasive ventilation, High flow nasal cannula, medicine.disease, respiratory tract diseases, 030228 respiratory system, Sample size determination, Anesthesia, Disease Progression, Female, medicine.symptom, Respiratory Insufficiency, business, Nasal cannula, Research Article
Abstract: Background Persistent hypercapnia after COPD exacerbation is associated with excess mortality and early rehospitalization. High Flow Nasal cannula (HFNC), may be theoretically an alternative to long-term noninvasive ventilation (NIV), since physiological studies have shown a reduction in PaCO2 level after few hours of treatment. In this clinical study we assessed the acceptability of HFNC and its effectiveness in reducing the level of PaCO2 in patients recovering from an Acute Hypercapnic Respiratory Failure (AHRF) episode. We also hypothesized that the response in CO2 clearance is dependent on baseline level of hypercapnia. Methods Fifty COPD patients recovering from an acute exacerbation and with persistent hypercapnia, despite having attained a stable pH (i.e. pH > 7,35 and PaCO2 > 45 mmHg on 3 consecutive measurements), were enrolled and treated with HFNC for at least 8 h/day and during the nighttime Results HFNC was well tolerated with a global tolerance score of 4.0 ± 0.9. When patients were separated into groups with or without COPD/OSA overlap syndrome, the “pure” COPD patients showed a statistically significant response in terms of PaCO2 decrease (p = 0.044). In addition, the subset of patients with a lower pH at enrolment were those who responded best in terms of CO2 clearance (score test for trend of odds, p = 0.0038). Conclusions HFNC is able to significantly decrease the level of PaCO2 after 72 h only in “pure” COPD patients, recovering from AHRF. No effects in terms of CO2 reduction were found in those with overlap syndrome. The present findings will help guide selection of the best target population and allow a sample size calculation for future long-term randomized control trials of HFNC vs NIV. Trial registration This study is registered with www. clinicaltrials.gov with identifier number NCT03759457.
Published: 2020
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25. Feasibility and clinical impact of out-of-ICU noninvasive respiratory support in patients with COVID-19-related pneumonia

Author: Emanuele Alberto Negri, Annalisa Carlucci, V. Marco Ranieri, Nicola Facciolongo, Gioachino Schifino, Luca Guidelli, Roberto Tonelli, Greta Spoladore, Paolo Amedeo Tillio, Cinzia Lastoria, Stefano Nava, Giovanna Arcaro, Andrea Vianello, Lara Pisani, Giovanni Guaraldi, Raffaele Scala, Mario Malerba, Roberto Dongilli, Luca Tabbì, C. Franco, Enrico Clini, Franco C., Facciolongo N., Tonelli R., Dongilli R., Vianello A., Pisani L., Scala R., Malerba M., Carlucci A., Negri E.A., Spoladore G., Arcaro G., Tillio P.A., Lastoria C., Schifino G., Tabbi L., Guidelli L., Guaraldi G., Marco Ranieri V., Clini E., and Nava S.
Subjects: Male, medicine.medical_treatment, medicine.disease_cause, law.invention, Cohort Studies, law, 80 and over, Continuous positive airway pressure, Hospital Mortality, Viral, Aged, 80 and over, Mortality rate, Middle Aged, Intensive care unit, Pulmonology, Original Article, Female, Coronavirus Infections, Nasal cannula, Human, Cohort study, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Pneumonia, Viral, Aged, COVID-19, Feasibility Studies, Humans, Length of Stay, Pandemics, SARS-CoV-2, Betacoronavirus, Noninvasive Ventilation, noninvasive ventilatory support, acute respiratory failure, SARS, Internal medicine, medicine, SARS, acute respiratory failure, Pandemic, Betacoronaviru, Coronavirus Infection, business.industry, Pneumonia, medicine.disease, Comorbidity, Feasibility Studie, noninvasive ventilatory support, Emergency medicine, Observational study, Cohort Studie, business
Abstract: Introduction The Coronavirus 2(SARS-CoV-2) outbreak spread rapidly in Italy and the lack of intensive care unit(ICU) beds soon became evident, forcing the application of noninvasive respiratory support(NRS) outside the ICU, raising concerns over staff contamination. We aimed to analyse the safety of the hospital staff, the feasibility, and outcomes of NRS applied to patients outside the ICU. Methods In this observational study, data from 670 consecutive patients with confirmed COVID-19 referred to the Pulmonology Units in nine hospitals between March 1st and May 10th,2020 were analysed. Data were collected including medication, mode and usage of the NRS (i.e. high-flow nasal cannula (HFNC), continuous positive airway pressure (CPAP), noninvasive ventilation(NIV)), length of stay in hospital, endotracheal intubation(ETI) and deaths. Results Forty-two health-care workers (11.4%) tested positive for infection, but only three of them required hospitalisation. Data are reported for all patients (69.3% male), whose mean age was 68 (sd 13) years. The PaO2/FiO2 ratio at baseline was 152±79, and the majority of patients (49.3%) were treated with CPAP. The overall unadjusted 30-day mortality rate was 26.9% with 16%, 30%, and 30%, while the total ETI rate was 27% with 29%, 25% and 28%, for HFNC, CPAP, and NIV, respectively, and the relative probability to die was not related to the NRS used after adjustment for confounders. ETI and length of stay were not different among the groups. Mortality rate increased with age and comorbidity class progression. Conclusions The application of NRS outside the ICU is feasible and associated with favourable outcomes. Nonetheless, it was associated with a risk of staff contamination., In patients with Coronavirus 2 infection and Acute Respiratory Failure, we demonstrated that the utilization of noninvasive respiratory support delivered outside the ICU, was feasible and effective, but associated with a risk of staff contamination
Published: 2020

26. Protecting healthcare workers from sars-cov-2 infection: Practical indications

Author: Stefano Nava, Cecilia Cisternino, Valentina Leo, Martina Ferioli, Paolo Palange, Lara Pisani, Ferioli M., Cisternino C., Leo V., Pisani L., Palange P., and Nava S.
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Health Personnel, Pneumonia, Viral, Airborne transmission, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Risk Factors, Health care, Pandemic, Medicine, Humans, 030212 general & internal medicine, Respiratory system, Intensive care medicine, Pandemics, lcsh:RC705-779, Hyperbaric Oxygenation, Betacoronaviru, business.industry, Transmission (medicine), Coronavirus Infection, SARS-CoV-2, Risk Factor, Respiratory disease, virus diseases, COVID-19, lcsh:Diseases of the respiratory system, medicine.disease, COVID-19 Drug Treatment, Pneumonia, 030228 respiratory system, business, Coronavirus Infections, Human
Abstract: The World Health Organization has recently defined the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection a pandemic. The infection, that may cause a potentially very severe respiratory disease, now called coronavirus disease 2019 (COVID-19), has airborne transmission via droplets. The rate of transmission is quite high, higher than common influenza. Healthcare workers are at high risk of contracting the infection particularly when applying respiratory devices such as oxygen cannulas or noninvasive ventilation. The aim of this article is to provide evidence-based recommendations for the correct use of “respiratory devices” in the COVID-19 emergency and protect healthcare workers from contracting the SARS-CoV-2 infection.
Published: 2020

27. ERS statement on chest imaging in acute respiratory failure

Author: Giovanni Sotgiu, Antonio Artigas, Peter M. Spieth, Aleksandar Grgic, Giuseppe Francesco Sferrazza Papa, Davide Chiumello, Leo M. A. Heunks, Paolo Navalesi, Maurizio Zompatori, Marcus J. Schultz, Klaus Markstaller, Giulia Michela Pellegrino, Lara Pisani, Belaid Bouhemad, David Rigau, Intensive care medicine, ACS - Pulmonary hypertension & thrombosis, Chiumello D., Sferrazza Papa G.F., Artigas A., Bouhemad B., Grgic A., Heunks L., Markstaller K., Pellegrino G.M., Pisani L., Rigau D., Schultz M.J., Sotgiu G., Spieth P., Zompatori M., Navalesi P., Intensive Care Medicine, AII - Inflammatory diseases, ACS - Diabetes & metabolism, and ACS - Microcirculation
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, Radiography, MEDLINE, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, medicine, Electric Impedance, Pulmonary Medicine, Humans, Acute respiratory failure, Intensive care medicine, Electrical impedance tomography, Ultrasonography, Mechanical ventilation, Heart Failure, Respiratory Distress Syndrome, Modalities, Chest imaging, medicine.diagnostic_test, business.industry, Pneumothorax, 030208 emergency & critical care medicine, Pneumonia, Europe, Pleural Effusion, 030228 respiratory system, Positron emission tomography, Positron-Emission Tomography, Radiography, Thoracic, business, Respiratory Insufficiency, Tomography, X-Ray Computed, Human
Abstract: Chest imaging in patients with acute respiratory failure plays an important role in diagnosing, monitoring and assessing the underlying disease. The available modalities range from plain chest X-ray to computed tomography, lung ultrasound, electrical impedance tomography and positron emission tomography. Surprisingly, there are presently no clear-cut recommendations for critical care physicians regarding indications for and limitations of these different techniques.The purpose of the present European Respiratory Society (ERS) statement is to provide physicians with a comprehensive clinical review of chest imaging techniques for the assessment of patients with acute respiratory failure, based on the scientific evidence as identified by systematic searches. For each of these imaging techniques, the panel evaluated the following items: possible indications, technical aspects, qualitative and quantitative analysis of lung morphology and the potential interplay with mechanical ventilation. A systematic search of the literature was performed from inception to September 2018. A first search provided 1833 references. After evaluating the full text and discussion among the committee, 135 references were used to prepare the current statement.These chest imaging techniques allow a better assessment and understanding of the pathogenesis and pathophysiology of patients with acute respiratory failure, but have different indications and can provide additional information to each other.
Published: 2019
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28. Noninvasive ventilation during weaning from prolonged mechanical ventilation

Author: Mara Paneroni, Stefano Nava, Nicolino Ambrosino, Lara Pisani, Annia Schreiber, Piero Ceriana, Michele Vitacca, Annalisa Carlucci, Ceriana P., Nava S., Vitacca M., Carlucci A., Paneroni M., Schreiber A., Pisani L., and Ambrosino N.
Subjects: Male, ARDS, Time Factors, Survival, medicine.medical_treatment, Hypercapnia, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Tracheostomy, Cause of Death, 030212 general & internal medicine, Prospective Studies, COPD, Simplified Acute Physiology Score, Respiration, Rehabilitation, Patient Discharge, Anesthesia, Breathing, Female, medicine.symptom, Prolonged weaning, Ventilator Weaning, Pulmonary and Respiratory Medicine, Respiratory mechanics, 03 medical and health sciences, medicine, Weaning, Humans, Survival rate, Device Removal, Aged, Mechanical ventilation, lcsh:RC705-779, Noninvasive Ventilation, business.industry, Non invasive ventilation, Tracheostomy decannulation, Respiratory mechanic, lcsh:Diseases of the respiratory system, Length of Stay, medicine.disease, Respiration, Artificial, Discontinuation, 030228 respiratory system, Feasibility Studies, Acidosis, Respiratory, Blood Gas Analysis, business, Follow-Up Studies
Abstract: Background and objective: Non invasive ventilation (NIV) is currently employed for weaning from invasive ventilation (IMV) in the acute setting but its use for weaning from prolonged ventilation is still occasional and not standardized. We wanted to evaluate whether a combined protocol of NIV and decannulation in tracheostomized patients needing prolonged mechanical ventilation was feasible and what would be the one-year outcome. Methods: We studied patients still dependent from invasive mechanical ventilation with the following inclusion criteria: a) tolerance of at least 8 h of unsupported breathing, b) progressive hypercapnia/acidosis after invasive ventilation discontinuation, c) good adaptation to NIV, d) favorable criteria for decannulation. These patients were switched from IMV to NIV and decannulated; then they were discharged on home NIV and followed-up for one year in order to evaluate survival and complications rate. Results: Data from patients consecutively admitted to a weaning unit were prospectively collected between 2005 and 2018. Out of 587 patients admitted over that period, 341 were liberated from prolonged mechanical ventilation. Fifty-one out of 147 unweaned patients (35%) were eligible for the protocol but only 46 were enrolled. After a mean length of stay of 35 days they were decannulated and discharged on domiciliary NIV. After one year, 38 patients were still alive (survival rate 82%) and 37 were using NIV with good adherence (only one patient was switched again to invasive ventilation). Conclusions: NIV applied to patients with failed weaning from prolonged IMV is feasible and can facilitate the decannulation process. Patients successfully completing this process show good survival rates and few complications. Keywords: Prolonged weaning, Non invasive ventilation, Tracheostomy decannulation, Survival, Respiratory mechanics, Rehabilitation
Published: 2019

29. Respiratory Mechanics and Diaphragmatic Dysfunction in COPD Patients Who Failed Non-Invasive Mechanical Ventilation

Author: Marchioni, Alessandro, Tonelli, Roberto, Fantini, Riccardo, Tabbì, Luca, Castaniere, Ivana, Livrieri, Francesco, Bedogni, Sabrina, Ruggieri, Valentina, Pisani, Lara, Nava, Stefano, Clini, Enrico, Marchioni A., Tonelli R., Fantini R., Tabbi L., Castaniere I., Livrieri F., Bedogni S., Ruggieri V., Pisani L., Nava S., and Clini E.
Subjects: Male, Diaphragm, transdiaphragmatic pressure, International Journal of Chronic Obstructive Pulmonary Disease, Respiratory failure, Pulmonary Disease, Chronic Obstructive, Pressure, Humans, Prospective Studies, Treatment Failure, Lung, Original Research, Aged, lcsh:RC705-779, Acute exacerbation of COPD, non-invasive mechanical ventilation, Noninvasive Ventilation, respiratory failure, lcsh:Diseases of the respiratory system, Middle Aged, acute exacerbation of COPD, Respiratory Mechanics, Female, Non-invasive mechanical ventilation, Lung Volume Measurements, Transdiaphragmatic pressure
Abstract: Alessandro Marchioni,1 Roberto Tonelli,1,2 Riccardo Fantini,1 Luca Tabbì,1 Ivana Castaniere,1,2 Francesco Livrieri,1,3 Sabrina Bedogni,4 Valentina Ruggieri,1 Lara Pisani,5 Stefano Nava,5 Enrico Clini1 1University Hospital of Modena, Pneumology Unit and Center for Rare Lung Diseases, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2PhD Course in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, Italy; 3Respiratory Disease Unit, Hospital Carlo Poma, Mantova, Italy; 4School of Medicine, University of Modena and Reggio Emilia, Modena, Italy; 5Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), University of Bologna, Bologna, ItalyCorrespondence: Roberto TonelliUniversity Hospital of Modena, Pneumology Unit and Center for Rare Lung Diseases, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Via del Pozzo, 71 – 41125, Modena, ItalyTel +39-342-7241672Email roberto.tonelli@me.com Skype roberto.tonelli150288Background: Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study, we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure.Methods: Twelve AECOPD patients with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017 to 2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end-expiratory lung volume (EELV) were measured after 30 mins of volume control mode MV. Subsequently, transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 mins of spontaneous breathing trial. Linear regression analysis and Pearson’s correlation coefficient served to assess associations.Results: Average Pdisniff was 23.3 cmH2O (standard deviation 29 cmH2O) with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=−0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=−0.55, p=0.06), EELV (r=−0.4, p=0.3), airway resistance (r=−0.2, p=0.54), chest wall, and total elastance (r=−0-01, p=0.96 and r=0.3, p=0.36, respectively). Significant linear inverse correlation was found between Pdisniff and the ratio betweenPdi assessed at tidal volume and Pdi sniff (r=−0.82, p=0.02).Conclusion: The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload.Keywords: acute exacerbation of COPD, non-invasive mechanical ventilation, respiratory failure, transdiaphragmatic pressure
Published: 2019

30. Patient–clinician alliance during prolonged mechanical ventilation 'never give up on a dream'

Author: Lara Pisani, Stefano Nava, Nava S., and Pisani L.
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Time Factors, Time Factor, media_common.quotation_subject, medicine.medical_treatment, Longitudinal Studie, Critical Care Nursing, Critical Care and Intensive Care Medicine, medicine, Humans, Longitudinal Studies, Prospective Studies, Dream, Intensive care medicine, Aged, media_common, Mechanical ventilation, business.industry, Editorials, Middle Aged, Respiration, Artificial, Alliance, Female, business, Ventilator Weaning, psychological phenomena and processes, Human
Abstract: In conclusion, this study, besides beingwell conducted and providing important clinical information, clarifies the issue that perception in medicine may be very misleading. Therefore, the patient and clinician, allied together, should never give up on the dream to liberate the patient from prolonged ventilation and recover a satisfactory quality of life
Published: 2019

31. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

Author: Vincenzo Salpietro1, 2 3, 140, Christine L. Dixon4, Hui Guo5, 6 140, Oscar D. Bello Stephanie Efthymiou 1, 4, Reza Maroofian1, Gali Heimer7, Lydie Burglen 8, Stephanie Valence 9, Erin Torti 10, Moritz Hacke11, Julia Rankin12, Huma Tariq1, Estelle Colin13, Vincent Procaccio13, Pasquale Striano2, 3, Kshitij Mankad15, Andreas Lieb 4, Sharon Chen16, Laura Pisani16, Conceicao Bettencourt 17, Roope Männikkö 1, Andreea Manole1, Alfredo Brusco 18, Enrico Grosso18, Giovanni Battista Ferrero19, Judith Armstrong-Moron20, Sophie Gueden21, Omer Bar-Yosef7, Michal Tzadok7, Kristin G. Monaghan10, Teresa Santiago-Sim10, Richard E. Person10, Megan T. Cho10, Rebecca Willaert10, Yongjin Yoo22, Jong-Hee Chae23, Yingting Quan6, Huidan Wu6, Tianyun Wang5, 6, Raphael A. Bernier24, Kun Xia6, Alyssa Blesson25, Mahim Jain25, Mohammad M. Motazacker26, Bregje Jaeger27, Amy L. Schneider 28, Katja Boysen28, Alison M. Muir 29, Candace T. Myers30, Ralitza H. Gavrilova31, Lauren Gunderson31, Laura Schultz-Rogers 31, Eric W. Klee31, David Dyment32, Matthew Osmond32, 33 34, Mara Parellada35, Cloe Llorente36, Javier Gonzalez-Peñas37, Angel Carracedo38, Arie Van Haeringen40, Claudia Ruivenkamp40, Caroline Nava41, Delphine Heron41, Rosaria Nardello42, Michele Iacomino43, Carlo Minetti2, Aldo Skabar44, Antonella Fabretto44, SYNAPS Study GroupMiquel Raspall-Chaure45, Michael Chez46, Anne Tsai47, Emily Fassi48, Marwan Shinawi48, John N. Constantino49, Rita De Zorzi50, Sara Fortuna 50, Fernando Kok51, Boris Keren41, Dominique Bonneau13, Murim Choi 22, Bruria Benzeev7, Federico Zara43, Heather C. Mefford29, Ingrid E. Scheffer28, Jill Clayton-Smith53, Alfons Macaya45, James E. Rothman4, Evan E. Eichler 5, Dimitri M. Kullmann 4, Henry Houlden 1, SYNAPS Study Group Michael G. Hanna1, Enrico Bugiardini1, Isabel Hostettler1, Benjamin O’Callaghan1, Alaa Khan1, Andrea Cortese1, Emer O’Connor1, Wai Y. Yau1, Thomas Bourinaris1, Rauan Kaiyrzhanov1, Viorica Chelban1, Monika Madej1, Maria C. Diana2, Maria S. Vari2, Marina Pedemonte2, Claudio Bruno2, Ganna Balagura3, Marcello Scala3, Chiara Fiorillo3, Lino Nobili3, Nancy T. Malintan4, Maria N. Zanetti4, Shyam S. Krishnakumar4, Gabriele Lignani4, James E. C. Jepson4, Paolo Broda43, Simona Baldassari43, Pia Rossi43, Floriana Fruscione43, Francesca Madia43, Monica Traverso43, Patrizia De-Marco43, Belen Pérez-Dueñas45, Francina Munell45, Yamna Kriouile57, Mohamed El-Khorassani57, Blagovesta Karashova58, Daniela Avdjieva58, Hadil Kathom58, Radka Tincheva58, Lionel Van-Maldergem59, Wolfgang Nachbauer60, Sylvia Boesch60, Antonella Gagliano61, Elisabetta Amadori62, Jatinder S. Goraya63, Tipu Sultan64, Salman Kirmani65, Shahnaz Ibrahim66, Farida Jan66, Jun Mine67, Selina Banu68, Pierangelo Veggiotti69, Gian V. Zuccotti69, Michel D. Ferrari70, Arn M. J. Van Den Maagdenberg70, Alberto Verrotti71, Gian L. Marseglia72, Salvatore Savasta72, Miguel A. Soler73, Carmela Scuderi74, Eugenia Borgione74, Roberto Chimenz75, Eloisa Gitto75, Valeria Dipasquale75, Alessia Sallemi75, Monica Fusco75, Caterina Cuppari75, Maria C. Cutrupi75, Martino Ruggieri76, Armando Cama77, Valeria Capra77, Niccolò E. Mencacci78, Richard Boles79, Neerja Gupta80, Madhulika Kabra80, Savvas Papacostas81, Eleni Zamba-Papanicolaou81, Efthymios Dardiotis82, Shazia Maqbool83, Nuzhat Rana84, Osama Atawneh85, Shen Y. Lim86, Farooq Shaikh87, George Koutsis88, Marianthi Breza88, Domenico A. Coviello89, Yves A. Dauvilliers90, Issam AlKhawaja91, Mariam AlKhawaja92, Fuad Al-Mutairi93, Tanya Stojkovic94, Veronica Ferrucci, Massimo Zollo, Fowzan S. Alkuraya96, Maria Kinali97, Hamed Sherifa98, Hanene Benrhouma99, Ilhem B. Y. Turki99, Meriem Tazir100, Makram Obeid101, Sophia Bakhtadze102, Nebal W. Saadi103, Maha S. Zaki104, Chahnez C. Triki105, Fabio Benfenati106, Stefano Gustincich106, Majdi Kara107, Vincenzo Belcastro108, Nicola Specchio109, Giuseppe Capovilla110, Ehsan G. Karimiani111, Ahmed M. Salih112, Njideka U. Okubadejo113, Oluwadamilola O. Ojo113, Olajumoke O. Oshinaike113, Olapeju Oguntunde113, Kolawole Wahab114, Abiodun H. Bello114, Sanni Abubakar115, Yahaya Obiabo116, Ernest Nwazor117, Oluchi Ekenze118, Uduak Williams119, Alagoma Iyagba120, Lolade Taiwo121, Morenikeji Komolafe122, Konstantin Senkevich123, Chingiz Shashkin124, Nazira Zharkynbekova125, Kairgali Koneyev126, Ganieva Manizha127, Maksud Isrofilov127, Ulviyya Guliyeva128, Kamran Salayev129, Samson Khachatryan130, Salvatore Rossi131, Gabriella Silvestri131, Nourelhoda Haridy132, Luca A. Ramenghi133, Georgia Xiromerisiou134, Emanuele David135, Mhammed Aguennouz136, Liana Fidani137, Cleanthe Spanaki138, Arianna Tucci139, University College of London [London] (UCL), Instituto Giannina Gaslini, Genoa, University of Genoa (UNIGE), University of Washington [Seattle], Institute of Neurology, Queen Square, London, King‘s College London, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, Molecular and Clinical Sciences Institute - St George’s [London, UK] (Genetics Research Centre), University of London [London], Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), GeneDx [Gaithersburg, MD, USA], Heidelberg University Hospital [Heidelberg], Royal Devon and Exeter NHS Foundation Trust [UK], Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Universita degli studi di Genova, Great Ormond Street Hospital for Children [London] (GOSH), The University of Sydney, Hofstra University [Hempstead], Università degli studi di Torino (UNITO), Hospital Sant Joan de Déu [Barcelona], Safra Children's Hospital, Seoul National University Hospital, Central South University [Changsha], Kennedy Krieger Institute [Baltimore], University of Amsterdam [Amsterdam] (UvA), University of Melbourne, Mayo Clinic [Rochester], Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, University of Ottawa [Ottawa], University of British Columbia (UBC), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Leiden [Leiden], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Palermo - University of Palermo, University of Trieste, Universitat Autònoma de Barcelona (UAB), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Children’s Hospital Colorado, University of Colorado Anschutz [Aurora], Washington University in Saint Louis (WUSTL), Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Department of Psychiatry, Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, University of Oxford [Oxford], University of São Paulo (USP), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Service de Pédiatrie, CHUR Poitiers, Seoul National University [Seoul] (SNU), Pediatric Neurology and Neuromuscular Diseases Unit, University of Manchester [Manchester], Yale University School of Medicine, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Salvy-Córdoba, Nathalie, Università degli studi di Genova = University of Genoa (UniGe), Tel Aviv University (TAU), Università degli studi di Torino = University of Turin (UNITO), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Trieste = University of Trieste, University of California (UC)-University of California (UC), University of Oxford, Universidade de São Paulo = University of São Paulo (USP), Yale School of Medicine [New Haven, Connecticut] (YSM), Salpietro V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S, Torti E, Hacke M, Rankin J, Tariq H, Colin E, Procaccio V, Striano P, Mankad K, Lieb A, Chen S, Pisani L, Bettencourt C, Männikkö R, Manole A, Brusco A, Grosso E, Ferrero GB, Armstrong-Moron J, Gueden S, Bar-Yosef O, Tzadok M, Monaghan KG, Santiago-Sim T, Person RE, Cho MT, Willaert R, Yoo Y, Chae JH, Quan Y, Wu H, Wang T, Bernier RA, Xia K, Blesson A, Jain M, Motazacker MM, Jaeger B, Schneider AL, Boysen K, Muir AM, Myers CT, Gavrilova RH, Gunderson L, Schultz-Rogers L, Klee EW, Dyment D, Osmond M, Parellada M, Llorente C, Gonzalez-Peñas J, Carracedo A, Van Haeringen A, Ruivenkamp C, Nava C, Heron D, Nardello R, Iacomino M, Minetti C, Skabar A, Fabretto A, SYNAPS Study Group, Raspall-Chaure M, Chez M, Tsai A, Fassi E, Shinawi M, Constantino JN, De Zorzi R, Fortuna S, Kok F, Keren B, Bonneau D, Choi M, Benzeev B, Zara F, Mefford HC, Scheffer IE, Clayton-Smith J, Macaya A, Rothman JE, Eichler EE, Kullmann DM, Houlden H, Salpietro, Vincenzo, Dixon, Christine L, Guo, Hui, Bello, Oscar D, Vandrovcova, Jana, Efthymiou, Stephanie, Maroofian, Reza, Heimer, Gali, Burglen, Lydie, Valence, Stephanie, Torti, Erin, Hacke, Moritz, Rankin, Julia, Tariq, Huma, Colin, Estelle, Procaccio, Vincent, Striano, Pasquale, Mankad, Kshitij, Lieb, Andrea, Chen, Sharon, Pisani, Laura, Bettencourt, Conceicao, Männikkö, Roope, Manole, Andreea, Brusco, Alfredo, Grosso, Enrico, Ferrero, Giovanni Battista, Armstrong-Moron, Judith, Gueden, Sophie, Bar-Yosef, Omer, Tzadok, Michal, Monaghan, Kristin G, Santiago-Sim, Teresa, Person, Richard E, Cho, Megan T, Willaert, Rebecca, Yoo, Yongjin, Chae, Jong-Hee, Quan, Yingting, Wu, Huidan, Wang, Tianyun, Bernier, Raphael A, Xia, Kun, Blesson, Alyssa, Jain, Mahim, Motazacker, Mohammad M, Jaeger, Bregje, Schneider, Amy L, Boysen, Katja, Muir, Alison M, Myers, Candace T, Gavrilova, Ralitza H, Gunderson, Lauren, Schultz-Rogers, Laura, Klee, Eric W, Dyment, David, Osmond, Matthew, Parellada, Mara, Llorente, Cloe, Gonzalez-Peñas, Javier, Carracedo, Angel, Van Haeringen, Arie, Ruivenkamp, Claudia, Nava, Caroline, Heron, Delphine, Nardello, Rosaria, Iacomino, Michele, Minetti, Carlo, Skabar, Aldo, Fabretto, Antonella, Raspall-Chaure, Miquel, Chez, Michael, Tsai, Anne, Fassi, Emily, Shinawi, Marwan, Constantino, John N, De Zorzi, Rita, Fortuna, Sara, Kok, Fernando, Keren, Bori, Bonneau, Dominique, Choi, Murim, Benzeev, Bruria, Zara, Federico, Mefford, Heather C, Scheffer, Ingrid E, Clayton-Smith, Jill, Macaya, Alfon, Rothman, James E, Eichler, Evan E, Kullmann, Dimitri M, Houlden, Henry, Salpietro1, Vincenzo, 3, 2, Dixon4, Christine L., Guo5, Hui, 140, 6, Bello Stephanie Efthymiou 1, Oscar D., Maroofian1, Reza, Heimer7, Gali, 8, Lydie Burglen, 9, Stephanie Valence, Torti 10, Erin, Hacke11, Moritz, Rankin12, Julia, Tariq1, Huma, Colin13, Estelle, Procaccio13, Vincent, Striano2, Pasquale, Mankad15, Kshitij, 4, Andreas Lieb, Chen16, Sharon, Pisani16, Laura, Bettencourt 17, Conceicao, 1, Roope Männikkö, Manole1, Andreea, Brusco 18, Alfredo, Grosso18, Enrico, Battista Ferrero19, Giovanni, Armstrong-Moron20, Judith, Gueden21, Sophie, Bar-Yosef7, Omer, Tzadok7, Michal, Monaghan10, Kristin G., Santiago-Sim10, Teresa, Person10, Richard E., Cho10, Megan T., Willaert10, Rebecca, Yoo22, Yongjin, Chae23, Jong-Hee, Quan6, Yingting, Wu6, Huidan, Wang5, Tianyun, Bernier24, Raphael A., Xia6, Kun, Blesson25, Alyssa, Jain25, Mahim, Motazacker26, Mohammad M., Jaeger27, Bregje, Schneider 28, Amy L., Boysen28, Katja, Muir 29, Alison M., Myers30, Candace T., Gavrilova31, Ralitza H., Gunderson31, Lauren, Schultz-Rogers 31, Laura, Klee31, Eric W., Dyment32, David, Osmond32, Matthew, 34, 33, Parellada35, Mara, Llorente36, Cloe, Gonzalez-Peñas37, Javier, Carracedo38, Angel, Van Haeringen40, Arie, Ruivenkamp40, Claudia, Nava41, Caroline, Heron41, Delphine, Nardello42, Rosaria, Iacomino43, Michele, Minetti2, Carlo, Skabar44, Aldo, Fabretto44, Antonella, Study GroupMiquel Raspall-Chaure45, Synap, Chez46, Michael, Tsai47, Anne, Fassi48, Emily, Shinawi48, Marwan, Constantino49, John N., De Zorzi50, Rita, Fortuna 50, Sara, Kok51, Fernando, Keren41, Bori, Bonneau13, Dominique, Choi 22, Murim, Benzeev7, Bruria, Zara43, Federico, Mefford29, Heather C., Scheffer28, Ingrid E., Clayton-Smith53, Jill, Macaya45, Alfon, Rothman4, James E., Eichler 5, Evan E., Kullmann 4 &amp, Dimitri M., 1, Henry Houlden, Hanna1, SYNAPS Study Group Michael G., Bugiardini1, Enrico, Hostettler1, Isabel, O’Callaghan1, Benjamin, Khan1, Alaa, Cortese1, Andrea, O’Connor1, Emer, Yau1, Wai Y., Bourinaris1, Thoma, Kaiyrzhanov1, Rauan, Chelban1, Viorica, Madej1, Monika, Diana2, Maria C., Vari2, Maria S., Pedemonte2, Marina, Bruno2, Claudio, Balagura3, Ganna, Scala3, Marcello, Fiorillo3, Chiara, Nobili3, Lino, Malintan4, Nancy T., Zanetti4, Maria N., Krishnakumar4, Shyam S., Lignani4, Gabriele, Jepson4, James E. C., Broda43, Paolo, Baldassari43, Simona, Rossi43, Pia, Fruscione43, Floriana, Madia43, Francesca, Traverso43, Monica, De-Marco43, Patrizia, Pérez-Dueñas45, Belen, Munell45, Francina, Kriouile57, Yamna, El-Khorassani57, Mohamed, Karashova58, Blagovesta, Avdjieva58, Daniela, Kathom58, Hadil, Tincheva58, Radka, Van-Maldergem59, Lionel, Nachbauer60, Wolfgang, Boesch60, Sylvia, Gagliano61, Antonella, Amadori62, Elisabetta, Goraya63, Jatinder S., Sultan64, Tipu, Kirmani65, Salman, Ibrahim66, Shahnaz, Jan66, Farida, Mine67, Jun, Banu68, Selina, Veggiotti69, Pierangelo, Zuccotti69, Gian V., Ferrari70, Michel D., Van Den Maagdenberg70, Arn M. J., Verrotti71, Alberto, Marseglia72, Gian L., Savasta72, Salvatore, Soler73, Miguel A., Scuderi74, Carmela, Borgione74, Eugenia, Chimenz75, Roberto, Gitto75, Eloisa, Dipasquale75, Valeria, Sallemi75, Alessia, Fusco75, Monica, Cuppari75, Caterina, Cutrupi75, Maria C., Ruggieri76, Martino, Cama77, Armando, Capra77, Valeria, Mencacci78, Niccolò E., Boles79, Richard, Gupta80, Neerja, Kabra80, Madhulika, Papacostas81, Savva, Zamba-Papanicolaou81, Eleni, Dardiotis82, Efthymio, Maqbool83, Shazia, Rana84, Nuzhat, Atawneh85, Osama, Lim86, Shen Y., Shaikh87, Farooq, Koutsis88, George, Breza88, Marianthi, Coviello89, Domenico A., Dauvilliers90, Yves A., Alkhawaja91, Issam, Alkhawaja92, Mariam, Al-Mutairi93, Fuad, Stojkovic94, Tanya, Ferrucci, Veronica, Zollo, Massimo, Alkuraya96, Fowzan S., Kinali97, Maria, Sherifa98, Hamed, Benrhouma99, Hanene, Turki99, Ilhem B. Y., Tazir100, Meriem, Obeid101, Makram, Bakhtadze102, Sophia, Saadi103, Nebal W., Zaki104, Maha S., Triki105, Chahnez C., Benfenati106, Fabio, Gustincich106, Stefano, Kara107, Majdi, Belcastro108, Vincenzo, Specchio109, Nicola, Capovilla110, Giuseppe, Karimiani111, Ehsan G., Salih112, Ahmed M., Okubadejo113, Njideka U., Ojo113, Oluwadamilola O., Oshinaike113, Olajumoke O., Oguntunde113, Olapeju, Wahab114, Kolawole, Bello114, Abiodun H., Abubakar115, Sanni, Obiabo116, Yahaya, Nwazor117, Ernest, Ekenze118, Oluchi, Williams119, Uduak, Iyagba120, Alagoma, Taiwo121, Lolade, Komolafe122, Morenikeji, Senkevich123, Konstantin, Shashkin124, Chingiz, Zharkynbekova125, Nazira, Koneyev126, Kairgali, Manizha127, Ganieva, Isrofilov127, Maksud, Guliyeva128, Ulviyya, Salayev129, Kamran, Khachatryan130, Samson, Rossi131, Salvatore, Silvestri131, Gabriella, Haridy132, Nourelhoda, Ramenghi133, Luca A., Xiromerisiou134, Georgia, David135, Emanuele, Aguennouz136, Mhammed, Fidani137, Liana, Spanaki138 &amp, Cleanthe, and Tucci139, Arianna
Subjects: Male, [SDV.GEN] Life Sciences [q-bio]/Genetics, Ion channels in the nervous system, Cohort Studies, fluids and secretions, Loss of Function Mutation, Receptors, AMPA, AMPA receptor, lcsh:Science, Child, reproductive and urinary physiology, AMPA receptor, GluA2, neurodevelopmental disorders, autism spectrum disorder, glutamatergic synaptic transmission, GRIA2, neurodevelopmental disorders, Developmental disorders, Neurodevelopmental disorders, Brain, Magnetic Resonance Imaging, Settore MED/26 - NEUROLOGIA, GluA2, Child, Preschool, Female, Adult, Heterozygote, Adolescent, Science, autism spectrum disorder, Article, Young Adult, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Intellectual Disability/genetics, Neurodevelopmental Disorders/genetics, Receptors AMPA/genetics, Intellectual Disability, mental disorders, Humans, Infant, Neurodevelopmental Disorders, Receptors, AMPA, GRIA2, Preschool, Ion channel in the nervous system, Developmental disorders, Synaptic development, NG sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, glutamatergic synaptic transmission, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, NG sequencing, Synaptic development, Ion channel in the nervous system, Next-generation sequencing, lcsh:Q
Abstract: AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission., Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”
Published: 2019
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32. Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3

Author: Pierre-Yves Renard, Marina Naldi, Joel L. Sussman, Stéphane Bach, Rémy Le Guével, Nunzio Denora, Jacques-Philippe Colletier, Sylvain Routier, Ludovic Jean, Leonardo Pisani, Marco Catto, Béatrice Josselin, Nicolas Coquelle, Israel Silman, Rosa Maria Iacobazzi, Frédéric Buron, Manuela Bartolini, Killian Oukoloff, Sandrine Ruchaud, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Alma Mater Studiorum University of Bologna (UNIBO), Plate-forme ImPACcell (ImPACcell), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Phophorylation de protéines et Pathologies Humaines (P3H), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro (UNIBA), Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Weizmann Institute of Science [Rehovot, Israël], Institut de Chimie Organique et Analytique (ICOA), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex SynOrg (ANR-11-LABX-0029) is acknowledged for a PhD fellowship to K. O. and the Agence Nationale de la Recherche (project MultiClick, grant number ANR-12-BS07-008-01) for financial support. This work was also partially supported by the INSA Rouen, Rouen Normandy University, the Centre National de la Recherche Scientifique and the Region Normandie (CRUNCh network)., Oukoloff K., Coquelle N., Bartolini M., Naldi M., Le Guevel R., Bach S., Josselin B., Ruchaud S., Catto M., Pisani L., Denora N., Iacobazzi R.M., Silman I., Sussman J.L., Buron F., Colletier J.-P., Jean L., Routier S., Renard P.-Y., Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fédération de recherche de Roscoff (FR2424), Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0029,SYNORG,Synthèse Organique : des molécules au vivant(2011), Laboratoire de Biologie Intégrative des Modèles Marins (LBI2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, Kinase, [SDV]Life Sciences [q-bio], [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, Crystallography, X-Ray, 01 natural sciences, Antineoplastic Agent, chemistry.chemical_compound, Glycogen Synthase Kinase 3, Synthesis, GSK-3, Drug Discovery, Dog, Enzyme Inhibitor, Enzyme Inhibitors, Cytotoxicity, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, 0303 health sciences, Crystallography, Molecular Structure, Synthesi, General Medicine, Alzheimer's disease, Acetylcholinesterase, Tacrine, Pharmacophore, medicine.drug, Human, SAR, Glycogen synthase kinase-3, Stereochemistry, Cell Survival, Cyclin-dependent kinase 5, Antineoplastic Agents, Ligand, Kinases, 03 medical and health sciences, Structure-Activity Relationship, Dogs, medicine, [CHIM.CRIS]Chemical Sciences/Cristallography, Structure–activity relationship, [CHIM]Chemical Sciences, Animals, Humans, 030304 developmental biology, Cell Proliferation, Pharmacology, Dose-Response Relationship, Drug, 010405 organic chemistry, Cell growth, Animal, Organic Chemistry, Triazoles, 0104 chemical sciences, chemistry, Drug Design, Butyrylcholinesterase, Triazole, Drug Screening Assays, Antitumor, Linker
Abstract: International audience; Both cholinesterases (AChE and BChE) and kinases, such as GSK-3α/β, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3α/β (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3α/β. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp.
Published: 2019
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33. Potential Diagnostic Properties of Chest Ultrasound in Thoracic Tuberculosis-A Systematic Review

Author: Roberto Copetti, Michaëla A. M. Huson, Damiano Pizzol, Annalisa Saracino, Valeria Lippolis, Luigi Pisani, Francesco Di Gennaro, Giovanni Putoto, Marcus J. Schultz, Laura Monno, Nicola Veronese, Di Gennaro, F., Pisani, L., Veronese, N., Pizzol, D., Lippolis, V., Saracino, A., Monno, L., Huson, M.A.M., Copetti, R., Putoto, G., and Schultz, M.J.
Subjects: medicine.medical_specialty, Tuberculosis, Pleural effusion, low-resource settings, Health, Toxicology and Mutagenesis, Radiography, lcsh:Medicine, Review, 03 medical and health sciences, 0302 clinical medicine, Biopsy, Medicine, Humans, 030212 general & internal medicine, tuberculosi, Ultrasonography, lung ultrasound, medicine.diagnostic_test, business.industry, Ultrasound, lcsh:R, Public Health, Environmental and Occupational Health, medicine.disease, Pneumonia, 030228 respiratory system, Pneumothorax, Effusion, tuberculosis, Radiology, business
Abstract: Background: Chest ultrasound (CUS) has been shown to be a sensitive and specific imaging modality for pneumothorax, pneumonia, and pleural effusions. However, the role of chest ultrasound in the diagnosis of thoracic tuberculosis (TB) is uncertain. We performed a systematic search in the medical literature to better define the potential role and value of chest ultrasound in diagnosing thoracic tuberculosis. Aim: To describe existing literature with regard to the diagnostic value of chest ultrasound in thoracic tuberculosis. Methods: MEDLINE, EMBASE, and Scopus databases were searched for relevant articles. We included studies that used chest ultrasound for the diagnosis or management of any form of thoracic tuberculosis, including pulmonary, pleural, mediastinal, and military forms. Results: We identified five main fields of chest ultrasound application: (1) Detection, characterization, and quantification of TB; (2) detection of residual pleural thickening after evacuation; (3) chest ultrasound-guided needle biopsy; (4) identification of pathologic mediastinal lymph nodes in children; and (5) identification of parenchymal ultrasound patterns. Effusion was also detected, in early stages, with signs of organization in 24–100% of patients. A low to moderate (10–23%), false negative rate was reported for chest ultrasound-guided needle biopsy. CUS was able to identify mediastinal lymph nodes in as many as 67% of patients with negative chest radiography. Conclusions: Very few studies with important methodological limitations analyze the role of chest ultrasound in the diagnosis of TB. The scarce available data suggests potential targets of future diagnostic or feasibility trials, such as the detection of tuberculosis–related pleural effusion, residual pleural thickening, lymphadenopathy, TB parenchymal patterns, or the use of CUS in biopsy guidance.
Published: 2018

34. Beyond the guidelines for non-invasive ventilation in acute respiratory failure: implications for practice

Author: Stephen Bourke, Laurent Brochard, Thomas Piraino, Mark W. Elliott, Lara Pisani, Bourke S.C., Piraino T., Pisani L., Brochard L., and Elliott M.W.
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, MEDLINE, Audit, Severity of Illness Index, law.invention, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, law, Severity of illness, Intubation, Intratracheal, Humans, Medicine, Non-invasive ventilation, Acute respiratory failure, 030212 general & internal medicine, Hypoxia, Intensive care medicine, Respiratory Distress Syndrome, Noninvasive Ventilation, business.industry, Patient Selection, Oxygen Inhalation Therapy, Guideline, Clinical Practice, 030228 respiratory system, Practice Guidelines as Topic, Ventilation (architecture), NIV, Respiratory Insufficiency, business
Abstract: Non-invasive ventilation is standard therapy in the management of both hypoxaemic and hypercapnic respiratory failure of various causes. The evidence base for its use and when and how it should be used has been reviewed in two recent guidelines. In this Series paper, we look beyond the guidelines to what is happening in everyday clinical practice in the real world, how patient selection can be refined to maximise the chances of a successful outcome, and emerging alternative therapies. Real-world application of non-invasive ventilation diverges from guideline recommendations, particularly with regard to patient selection and timing of initiation. To improve patient outcomes education programmes need to stress these issues and the effectiveness of non-invasive ventilation that is delivered needs to be monitored by regular audit.
Published: 2018

35. Use of Nasal High Flow in Stable COPD: Rationale and Physiology

Author: Lara Pisani, Maria Laura Vega, Pisani L., and Vega M.L.
Subjects: Pulmonary and Respiratory Medicine, Mucociliary clearance, Dead space, medicine.medical_treatment, Partial Pressure, oxygen therapy, medicine.disease_cause, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Oxygen therapy, Positive airway pressure, Humans, Medicine, Cannula, 030212 general & internal medicine, chronic respiratory failure, COPD, Lung, business.industry, Chronic obstructive pulmonary disease, Airway Resistance, high flow nasal cannula, Oxygen Inhalation Therapy, respiratory system, Carbon Dioxide, medicine.disease, respiratory tract diseases, Oxygen, medicine.anatomical_structure, 030228 respiratory system, Mucociliary Clearance, Anesthesia, business, Airway, Pulmonary Ventilation, Nasal cannula, Human
Abstract: High-flow nasal cannula (HFNC) is a device able to deliver heated and humidified oxygen at high flows (up to 60L/minutes). Potential benefits of HFNC are several and include the improvement of lung mucociliary clearance, the washout of upper airway dead space, the generation of a low level of positive airway pressure (PEEP effect), the decrease in inspiratory resistance and at the same time the increase in expiratory resistance. The present review aimed to describe the evidence surrounding the use of HFNC in stable chronic obstructive pulmonary disease patients.
Published: 2017

36. Noninvasive ventilation in acute respiratory failure: which recipe for success?

Author: Lara Pisani, Raffaele Scala, Scala R., and Pisani L.
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Psychomotor agitation, medicine.medical_treatment, Clinical Decision-Making, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Intubation, Intratracheal, medicine, Humans, Intubation, Acute respiratory failure, Intensive care medicine, lcsh:RC705-779, Mechanical ventilation, Coma, Noninvasive Ventilation, business.industry, Patient Selection, Risk Factor, 030208 emergency & critical care medicine, lcsh:Diseases of the respiratory system, Treatment Outcome, 030228 respiratory system, Haemodynamic instability, Acute Disease, Breathing, Noninvasive ventilation, medicine.symptom, Respiratory Insufficiency, business, Human
Abstract: Noninvasive positive-pressure ventilation (NPPV) to treat acute respiratory failure has expanded tremendously over the world in terms of the spectrum of diseases that can be successfully managed, the locations of its application and achievable goals.The turning point for the successful expansion of NPPV is its ability to achieve the same physiological effects as invasive mechanical ventilation with the avoidance of the life-threatening risks correlated with the use of an artificial airway.Cardiorespiratory arrest, extreme psychomotor agitation, severe haemodynamic instability, nonhypercapnic coma and multiple organ failure are absolute contraindications for NPPV. Moreover, pitfalls of NPPV reduce its rate of success; consistently, a clear plan of what to do in case of NPPV failure should be considered, especially for patients managed in unprotected setting. NPPV failure is likely to be reduced by the application of integrated therapeutic tools in selected patients handled by expert teams.In conclusion, NPPV has to be considered as a rational art and not just as an application of science, which requires the ability of clinicians to both choose case-by-case the best “ingredients” for a “successful recipe” (i.e.patient selection, interface, ventilator, interface,etc.) and to avoid a delayed intubation if the ventilation attempt fails.
Published: 2018
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37. Noninvasive Ventilation in Critically Ill Patients

Author: Cesare Gregoretti, Andrea Cortegiani, Lara Pisani, Vito Marco Ranieri, Gregoretti, C., Pisani, L., Cortegiani, A., Ranieri, V.M., Gregoretti, Cesare, Pisani, Lara, Cortegiani, Andrea, and Ranieri, Vito Marco
Subjects: lung disease, procedure, medicine.medical_treatment, treatment indication, treatment contraindication, Review, Critical Care and Intensive Care Medicine, Acute respiratory failure, intensive care unit, equipment design, Continuous positive airway pressure, Hospital Mortality, Respiratory system, Nose, risk reduction, sleep disorder, emergency health service, Respiratory Distress Syndrome, emergency ward, critical illne, humidifier, General Medicine, adult respiratory distress syndrome, Intermittent positive pressure ventilation, Critically patient, respiratory circuit, medicine.anatomical_structure, priority journal, positive end expiratory pressure, Noninvasive ventilation, Emergency Service, Hospital, medicine.medical_specialty, ventilator, Critical Illness, ward, hypercapnic nonchronic obstructive pulmonary disease, critically ill patient, Respiratory Distress Syndrome, Adult, Critical Illne, obesity hypoventilation syndrome, medicine, Humans, human, Intensive care medicine, lung edema, Mechanical ventilation, general ward, hypoxemia, Noninvasive Ventilation, air humidification, Critically ill, business.industry, practice guideline, Respiratory Distress Syndrome, Adult, neurally adjusted ventilator assist, respiratory intensive care unit, mortality, acute cardiogenic pulmonary edema, hypercapnic chronic obstructive pulmonary disease, disease exacerbation, noninvasive positive pressure ventilation, business, chronic obstructive lung disease, respiratory therapeutic device
Abstract: Since its first application in the late 1980s, noninvasive ventilation (NIV) has been the first-line intervention for certain forms of acute respiratory failure. NIV may be delivered through the patient's mouth, nose, or both using noninvasive intermittent positive pressure ventilation or continuous positive airway pressure. When applied appropriately, NIV may reduce morbidity and mortality and may avert iatrogenic complications and infections associated with invasive mechanical ventilation. This article provides physicians and respiratory therapists with a comprehensive, practical guideline for using NIV in critical care. © 2015 Elsevier Inc.
Published: 2015

38. Socio-Economic and Clinical Factors as Predictors of Disease Evolution and Acute Events in COPD Patients

Author: Corrado Zenesini, Sabrina Angelini, Silvana Hrelia, Alessandro Zanasi, Muriel Assunta Musti, Paolo Pandolfi, Elisa Stivanello, Cristina Angeloni, Lara Pisani, Patrizia Hrelia, Francesca Maffei, Pandolfi P, Zanasi A, Musti MA, Stivanello E, Pisani L, Angelini S, Maffei F, Hrelia S, Angeloni C, Zenesini C, and Hrelia P
Subjects: Male, Spirometry, medicine.medical_specialty, lcsh:Medicine, Kaplan-Meier Estimate, Severity of Illness Index, Pulmonary Disease, Chronic Obstructive, Risk Factors, Internal medicine, Severity of illness, medicine, COPD, Humans, Respiratory function, Intensive care medicine, lcsh:Science, Life Style, Survival analysis, Aged, Proportional Hazards Models, Multidisciplinary, Anthropometry, medicine.diagnostic_test, Proportional hazards model, business.industry, Body Weight, lcsh:R, Middle Aged, medicine.disease, respiratory tract diseases, Hospitalization, Social Class, Disease Progression, Female, lcsh:Q, Underweight, medicine.symptom, business, Body mass index, Research Article
Abstract: Background Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Methods Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant’Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. Results 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival curves by COPD stage with lower event-free probability in very severe COPD stage. Significant risk factors for acute events were: underweight (HR = 4.08; 95% CI 1.01–16.54), having two or more comorbidities (HR = 4.71; 95% CI 2.52–8.83), belonging to moderate (HR = 3.50; 95% CI 1.01–12.18) or very severe COPD stage (HR = 8.23; 95% CI 2.35–28.85). Conclusions Our findings indicate that fragility is associated with COPD stage and that comorbidities and the low body mass index are predictors of mortality or hospitalization. Besides spirometric analyses, FeNO measure and comorbidities, body mass index could also be considered in the management and monitoring of COPD patients.
Published: 2015

39. Neurally adjusted non-invasive ventilation in patients with chronic obstructive pulmonary disease: does patient–ventilator synchrony matter?

Author: Lara Pisani, Stefano Nava, Nava, S., and Pisani, L.
Subjects: Adult, Male, medicine.medical_specialty, Sedation, Population, Pulmonary disease, Pressure support ventilation, Critical Care and Intensive Care Medicine, mechanical ventilation asynchrony, Intermittent Positive-Pressure Ventilation, Pulmonary Disease, Chronic Obstructive, medicine, Neurally adjusted ventilatory assist, Non-invasive ventilation, Humans, Intensive care medicine, education, Interactive Ventilatory Support, Aged, education.field_of_study, Noninvasive Ventilation, business.industry, Respiration, Middle Aged, Intensive Care Units, Breathing, Commentary, Female, medicine.symptom, business, Algorithms
Abstract: Delivering synchronous assist during non-invasive ventilation (NIV) is challenging with flow- or pressure-controlled ventilators, especially in patients with chronic obstructive pulmonary disease (COPD). Neurally adjusted ventilatory assist (NAVA) uses diaphragm electrical activity (EAdi) to control the ventilator. We evaluated patient-ventilator interaction in patients with COPD during NIV with pressure support ventilation (PSV) and NAVA using a recently introduced automated analysis.Twelve COPD patients underwent three 30-minute trials: 1) PSV with dedicated NIV ventilator (NIV-PSVVision), 2) PSV with intensive care unit (ICU) ventilator (NIV-PSVServo-I), and 3) with NIV-NAVA. EAdi, flow, and airway pressure were recorded. Patient-ventilator interaction was evaluated by comparing airway pressure and EAdi waveforms with automated computer algorithms. The NeuroSync index was calculated as the percentage of timing errors between airway pressure and EAdi.The NeuroSync index was higher (larger error) for NIV-PSVVision (24 (IQR 15 to 30) %) and NIV-PSVServo-I (21 (IQR 15 to 26) %) compared to NIV-NAVA (5 (IQR 4 to 7) %; P0.001). Wasted efforts, trigger delays and cycling-off errors were less with NAVA (P0.05 for all). The NeuroSync index and the number of wasted efforts were strongly correlated (r2 = 0.84), with a drastic increase in wasted efforts after timing errors reach 20%.In COPD patients, non-invasive NAVA improves patient-ventilator interaction compared to PSV, delivered either by a dedicated or ICU ventilator. The automated analysis of patient-ventilator interaction allowed for an objective detection of patient-ventilator interaction during NIV. In addition, we found that progressive mismatch between neural effort and pneumatic timing is associated with wasted efforts.
Published: 2014

40. A randomized, placebo-controlled, double-blind trial on the management of post-infective cough by inhaled ipratropium and salbutamol administered in combination

Author: Antonio Maria Morselli-Labate, Alessandro Zanasi, Lara Pisani, Massimiliano Mazzolini, Marianna Mastroroberto, Paolo Pandolfi, Marzia Lecchi, Manuela Del Forno, Elisa Fabbri, Stefano Nava, Zanasi, A, Lecchi, M, Del Forno, M, Fabbri, E, Mastroroberto, M, Mazzolini, M, Pisani, L, Pandolfi, P, Nava, S, Morselli Labate, A, Alessandro Zanasi, Marzia Lecchi, Manuela Del Forno, Elisa Fabbri, Marianna Mastroroberto, Massimiliano Mazzolini, Lara Pisani, Paolo Pandolfi, Stefano Nava, and Antonio Maria Morselli-Labate
Subjects: Spirometry, Adult, Male, Pulmonary and Respiratory Medicine, medicine.drug_class, Night cough, Salbutamol, Ipratropium bromide, RCT cough bronchodilators, Placebo, Post-viral cough, Young Adult, Double-Blind Method, Administration, Inhalation, Anticholinergic, Humans, Medicine, Respiratory Tract Infection, Albuterol, Pharmacology (medical), Adverse effect, Respiratory Tract Infections, Bronchodilator Agent, Aged, medicine.diagnostic_test, business.industry, Ipratropium, Biochemistry (medical), Upper respiratory tract infection, Middle Aged, medicine.disease, Bronchodilator Agents, respiratory tract diseases, Cough, Anesthesia, Drug Therapy, Combination, Female, business, medicine.drug, Human
Abstract: Post-viral cough is a type of cough originating from upper respiratory tract infections that persists after the infection is resolved. Although it was hypothesized that bronchodilators might have a role in the management of post-viral cough, a clear demonstration of their efficacy is missing. Therefore, we tested the efficacy of a combination of a β-agonist and an anticholinergic agent in reducing post-viral cough with a randomized, double blind, placebo controlled clinical trial. Patients were treated for 10 days with either a nebulized combination of salbutamol 1.875 mg/0.5 mL and ipratropium bromide 0.375 mg/0.5 mL, or a placebo, and followed up for another 10 days. Daytime and nighttime cough severity and spirometry testing were assessed before starting treatment, after 10 and 20 days. Ninety-two patients were randomized to receive placebo (n = 46) or the active treatment (n = 46); nine of them (4 in the placebo group, 5 in the active treatment group) dropped out from the study. Daytime and nighttime cough severity were significantly reduced in both groups during the study period, but the reduction was more prominent in the active treatment group vs. placebo after 10 days of treatment (P = 0.003 for day cough; P = 0.061 for night cough), whereas at the end of follow-up period cough severity was comparable between the two groups. Small but significant increases in spirometric parameters were observed in the active treatment vs. placebo group, although at the end of follow-up these values returned to be comparable to placebo. The frequency of adverse events was not significantly different between the two groups of patients. We concluded that a combination of a β-agonist and an anticholinergic agent can effectively reduce post-viral cough, and can thus represent a valid option for this type of cough.
Published: 2014

41. Opposite behavior of plasma levels surfactant protein type B and receptor for advanced glycation end products in pulmonary sarcoidosis

Author: Agnese Ricotta, Alberto Ricci, Stefania Ghilardi, Lara Pisani, Piergiuseppe Agostoni, Salvatore Mariotta, Damiano Magrì, Cristina Banfi, Alessandro Onofri, Filippo Maria Cauti, Magri D., Mariotta S., Banfi C., Ricotta A., Onofri A., Ricci A., Pisani L., Cauti F.M., Ghilardi S., and Agostoni P.
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Pathology, Receptor for Advanced Glycation End Products, Vital Capacity, Pilot Projects, Lung injury, Gastroenterology, Group A, Pulmonary function testing, RAGE (receptor), Surfactant protein type B, Sarcoidosis, Pulmonary, Glycation, Internal medicine, Forced Expiratory Volume, Medicine, Humans, Pilot Project, Receptors, Immunologic, Receptor, lung diffusion capacity, surfactant protein type b, cardiopulmonary exercise test, rage, pulmonary sarcoidosis, Cardiopulmonary exercise test, Aged, Lung, Pulmonary Surfactant-Associated Protein B, business.industry, Pulmonary sarcoidosis, Biomarker, Middle Aged, medicine.disease, Lung diffusion capacity, RAGE, medicine.anatomical_structure, Case-Control Studies, Receptor for Advanced Glycation End Product, Exercise Test, Pulmonary Diffusing Capacity, Female, Sarcoidosis, business, Case-Control Studie, Pulmonary sarcoidosi, Biomarkers, Human
Abstract: Background No biological marker is currently available for evaluating pulmonary involvement and/or for monitoring the clinical course of sarcoidosis. The present pilot study focused on possible relationships between circulating plasma levels of surfactant protein type B (SP-B) and plasma receptor for advanced glycation end products (RAGE) and lung function abnormalities in patients with pulmonary sarcoidosis, since both SP-B and RAGE have been previously suggested as lung injury markers. The plasmatic levels of these two proteins were also investigated with respect to functional capacity, as assessed by a cardiopulmonary exercise test (CPET). Methods Thirty pulmonary sarcoidosis outpatients and fifteen volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B and RAGE plasma levels were also determined. Patients were then categorized according to the severity of their pulmonary involvement, as assessed in terms of lung diffusion for carbon monoxide (DL CO) values. Results Group B showed SP-B levels higher and RAGE levels lower than Group A and Control Group (p < 0.01). Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B levels did not differ between these two groups. A significant univariate relationship was found between both SP-B and RAGE and several lung function data, particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DL CO: r: -0.451, p = 0.012). Conclusions Circulating plasma levels of SP-B and RAGE showed an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are directly related to alveolar unit damage, supporting a possible role of SP-B as a marker of disease severity in these patients. Differently, RAGE decreases in severe sarcoidosis, suggesting more complex underlying mechanisms.
Published: 2013

42. NT-proAtrial Natriuretic Peptide as a possible biomarker of cardiopulmonary involvement in sarcoidosis

Author: Alberto Ricci, Lara Pisani, Piergiuseppe Agostoni, Agnese Ricotta, Massimo Volpe, Damiano Magrì, Pierdonato Bruno, Filippo Maria Cauti, Salvatore Mariotta, Alessandro Onofri, Simona Marchitti, Speranza Rubattu, Magri D., Agostoni P., Ricotta A., Pisani L., Cauti F.M., Onofri A., Bruno P., Ricci A., Volpe M., Marchitti S., Mariotta S., and Rubattu S.
Subjects: Male, medicine.medical_specialty, Protein Precursor, Sarcoidosis, medicine.drug_class, Hypertension, Pulmonary, Ventricular Dysfunction, Right, Doppler echocardiography, Sarcoidosi, Pulmonary function testing, Tissue Doppler imaging, Atrial natriuretic peptide, DLCO, Internal medicine, Internal Medicine, Natriuretic peptide, Humans, Medicine, Familial Primary Pulmonary Hypertension, Protein Precursors, Multivariate Analysi, Aged, Respiratory Function Test, Lung, medicine.diagnostic_test, business.industry, myocardial dysfunction, lung diffusion capacity, pulmonary sarcoidosis, atrial natriuretic peptide, tissue doppler imaging, Biomarker, Middle Aged, medicine.disease, Myocardial dysfunction, Lung diffusion capacity, Echocardiography, Doppler, Respiratory Function Tests, medicine.anatomical_structure, Multivariate Analysis, Cardiology, Vascular resistance, Female, Vascular Resistance, business, Biomarkers, Pulmonary sarcoidosi, Atrial Natriuretic Factor, Human
Abstract: Background: Lung diffusion for carbon monoxide (DLCO) has been shown to associate with the risk of pulmonary arterial hypertension development and, most likely, with right ventricular (RV) myocardial dysfunction in sarcoidosis patients. Besides its known role as a marker of left ventricular dysfunction, experimental evidence suggests a role of NT-proAtrial Natriuretic Peptide (NT-proANP) also in modulating pulmonary circulation. We therefore investigated possible relationships between NT-proANP, lung diffusion impairment and RV dysfunction. Methods: Thirty-two pulmonary sarcoidosis outpatients and eighteen volunteers underwent full clinical assessment, including full lung function tests and Doppler echocardiography integrated with tissue Doppler imaging (TDI) study. Resting circulating NT-proBNP and NT-proANP plasma levels were also determined. Results: NT-proANP and RV-myocardial performance index (RV-MPI) were significantly higher in those patients with the greatest DL CO impairment, whereas no differences were found for NT-proBNP values. At multivariable analysis, only DLCO (β: - 0.496; standard error: 3.38; p = 0.000) and RV-MPI (β: 0.373; standard error: 6.56; p = 0.031) remained significantly associated with NT-proANP levels. Conclusions: Our finding may support a key role of NT-proANP in the complex mechanisms underlying modulation of lung function. An early increase in pulmonary vascular resistance may stimulate NT-proANP increase, thus explaining its association with signs of early RV myocardial dysfunction. This hypothesis warrants further confirmation. © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Published: 2013

43. Patient-ventilator asynchronies: may the respiratory mechanics play a role?

Author: Piero Ceriana, Annalisa Carlucci, Stefano Nava, Lara Pisani, Alberto Malovini, Carlucci A, Pisani L, Ceriana P, Malovini A, and Nava S
Subjects: Male, medicine.medical_specialty, Pediatrics, respiratory mechanic, Respiratory pattern, Respiratory physiology, Critical Care and Intensive Care Medicine, Internal medicine, medicine, Humans, In patient, Prospective Studies, Prospective cohort study, Aged, business.industry, Incidence (epidemiology), respiratory failure, Middle Aged, Respiration, Artificial, Asynchrony (computer programming), Chronic Disease, Cardiology, Breathing, Respiratory Mechanics, Commentary, Female, business, Respiratory Insufficiency, Chronic respiratory failure
Abstract: The mechanisms leading to patient/ventilator asynchrony has never been systematically assessed. We studied the possible association between asynchrony and respiratory mechanics in patients ready to be enrolled for a home non-invasive ventilatory program. Secondarily, we looked for possible differences in the amount of asynchronies between obstructive and restrictive patients and a possible role of asynchrony in influencing the tolerance of non-invasive ventilation (NIV). METHODS: The respiratory pattern and mechanics of 69 consecutive patients with chronic respiratory failure were recorded during spontaneous breathing. After that patients underwent non-invasive ventilation for 60 minutes with a "dedicated" NIV platform in a pressure support mode during the day. In the last 15 minutes of this period, asynchrony events were detected and classified as ineffective effort (IE), double triggering (DT) and auto-triggering (AT). RESULTS: The overall number of asynchronies was not influenced by any variable of respiratory mechanics or by the underlying pathologies (that is, obstructive vs restrictive patients). There was a high prevalence of asynchrony events (58% of patients). IEs were the most frequent asynchronous events (45% of patients) and were associated with a higher level of pressure support. A high incidence of asynchrony events and IE were associated with a poor tolerance of NIV. CONCLUSIONS: Our study suggests that in non-invasively ventilated patients for a chronic respiratory failure, the incidence of patient-ventilator asynchronies was relatively high, but did not correlate with any parameters of respiratory mechanics or underlying disease
Published: 2013

44. Interfaces for noninvasive mechanical ventilation: technical aspects and efficiency

Author: Lara Pisani, Carlucci, A., Nava, S., Pisani, L, Carlucci, A, and Nava, S
Subjects: Pulmonary Disease, Chronic Obstructive, Noninvasive Ventilation, Patient Satisfaction, Respiratory Physiological Phenomena, Humans, Equipment Failure, Respiratory Dead Space, Respiratory Insufficiency, Human
Abstract: Noninvasive mechanical ventilation (NIV) has become a standard of care in select patients with both hypercapnic and non-hypercapnic acute respiratory failure (ARF). Consequent to the increasing use of NIV, new interfaces of different designs, shapes, sizes, and materials have been proposed for clinical use in recent years. The aim of this report is to examine the most relevant physiological aspects related to the choice of interface with particular emphasis on the problems related to dead space and air leaks that may affect the synchrony between the patient and the machine, ultimately determining the patient's compliance and therefore NIV success.
Published: 2012

45. Different tracheotomy tube diameters influence diaphragmatic effort and indices of weanability in difficult to wean patients

Author: Chiara Mega, Cesare Gregoretti, Ilaria Valentini, Lara Pisani, Luca Fasano, Stefano Nava, Eva Tonveronachi, Valentini I, Tonveronachi E, Gregoretti C, Mega C, Fasano L, Pisani L, and Nava S.
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Respiratory rate, medicine.medical_treatment, Diaphragm, weanability, Diaphragmatic breathing, Pulmonary compliance, Critical Care and Intensive Care Medicine, Work of breathing, Tracheotomy, diaphragmatic effort, medicine, Intubation, Intratracheal, Intubation, Humans, Tidal volume, Aged, Work of Breathing, Aged, 80 and over, business.industry, General Medicine, Equipment Design, Diaphragm (structural system), Surgery, tracheotomy, Female, business, Nuclear medicine, Energy Metabolism, Ventilator Weaning
Abstract: OBJECTIVE: To determine the effects of different tracheotomy tube sizes on diaphragm effort and weanability indices. METHODS: Ten tracheotomized and difficult to wean subjects were randomized to 2 T-piece trials, with different tracheotomy tube diameters: inner diameters 8 mm and 6.5 mm. Diaphragm pressure-time product per min. (PTP(di/min)), lung compliance and resistance (C(L) and R(L)), breathing pattern, tension-time index of the diaphragm (TT(di)), and the ratio of breathing frequency to tidal volume (f/V(T)) were recorded. In an in vitro model, the flow-pressure relationship was measured using the 2 tracheotomy tubes and 2 endotracheal tubes of the same diameter. RESULTS: The use of a smaller diameter resulted in an increase of PTP(di) (337.63 ± 194.35 cm H(2)O · s/min vs 263.28 ± 156.23 cm H(2)O · s/min for 6.5 mm and 8 mm, respectively, P = .004) and R(L) (16.74 ± 8.10 cm H(2)O · s/min vs 11.72 ± 7.88 cm H(2)O · s/min, respectively, P = .008). Both weanability indices were also significantly higher using the smaller tube: f/V(T) 93.32 ± 20.91 vs 77.06 ± 19.26 for 6.5 mm and 8 mm, respectively, P < .02; TT(di) 0.09 ± 0.052 vs 0.08 ± 0.04, respectively, P < .02. In vitro measurements confirmed that the resistances were higher with the smaller diameter and similar between the tracheotomy tubes and the endotracheal tubes of the same diameters. CONCLUSIONS: In tracheotomized difficult to wean subjects the decrease of the tracheotomy tube size was associated with an increased PTP(di), f/V(T), and TT(di), that were otherwise normal, using a higher diameter. The in vitro study showed that the resistances increased similarly for tracheotomy tube and endotracheal tube, decreasing the diameter and increasing the flows.
Published: 2012

46. Inverse relationship between scores on the quality of life questionnaire SF-12 and on the Aging Males' Symptoms scale in Italian men

Author: Giorgio Valenti, Massimo Capone, Gianni Forti, Marco Grasso, Vicenzo Mirone, Francesca Chiaffarino, Elena Ricci, Gianluca Appiani, Emilio Corti, Davide Fabbrica, Enzo Ferrario, Sergio Ghezzi, Marco Grendele, Paolo Maroni, Gianbattista Mazzoleni, Mario Nicolussi, Antonio Pinnavaria, Alberto Rossi, Vittorino Sala, Silvana Santoro, Gaetano Autore, Giovanni Avvento, Roberto Barra, Dario Brunetti, Aurelio Catalano, Vincenzo Girardi, Giuseppe Iovane, Federico Lettieri, Sergio Marescotti, Nicola Pelaggi, Gennaro Sica, Stefano Delcanale, Beatrice M. Gorreri, Carlo Maini, Fabrizio Peri, Emilio Sani, Mario Sisto, Anita Sullam, Giovanni Zanardi, Giuseppe Burgio, Alessandro Bussotti, Lucia Caldini, Lucia Gianelli, Nadia Gianni, Massimo Giuntoli, Massimo Guarducci, Alessio Nastruzzi, Rachele Pacileo, Riccardo Pirozzi, Lorenzo Pisani, Maurizio Puliti, Paola Rafanelli, Paolo Baron, Filippo Cocomazzi, Giovanni Cominetti, Gianfranco Matera, Gianfranco Panizzo, Denis Podrecca, Ivana Rupalti, Paolo Spagnul, Laura Ivana Tonelli, Onorino Venturini, Claudio Nardo, Fabio Parazzini, null Aging Male Italian Epidemiological, Valenti, G, Capone, M, Forti, G, Grasso, M, Mirone, Vincenzo, Chiaffarino, F, Ricci, E, Appiani, G, Corti, E, Fabbrica, D, Ferrario, E, Ghezzi, S, Grendele, M, Maroni, P, Mazzoleni, G, Nicolussi, M, Pinnavaria, A, Rossi, A, Sala, V, Santoro, S, Autore, G, Avvento, G, Barra, R, Brunetti, D, Catalano, A, Girardi, V, Iovane, G, Lettieri, F, Marescotti, S, Pelaggi, N, Sica, G, Delcanale, S, Gorreri, Bm, Maini, C, Peri, F, Sani, E, Sisto, M, Sullam, A, Zanardi, G, Burgio, G, Bussotti, A, Caldini, L, Gianelli, L, Gianni, N, Giuntoli, M, Guarducci, M, Nastruzzi, A, Pacileo, R, Pirozzi, R, Pisani, L, Puliti, M, Rafanelli, P, Baron, P, Cocomazzi, F, Cominetti, G, Matera, G, Panizzo, G, Podrecca, D, Rupalti, I, Spagnul, P, Tonelli, Li, Venturini, O, Nardo, C, Parazzini, F, and Aging Male Italian Epidemiological Study, G. r. o. u. p.
Subjects: Gerontology, Male, medicine.medical_specialty, Aging, Cross-sectional study, Quality of life, Risk Factors, Diabetes mellitus, Surveys and Questionnaires, Epidemiology, medicine, Humans, Myocardial infarction, Aged, business.industry, Odds ratio, Middle Aged, medicine.disease, Increased risk, Cross-Sectional Studies, Italy, Cardiovascular Diseases, Scale (social sciences), Physical therapy, Quality of Life, Geriatrics and Gerontology, business
Abstract: To analyse the relation between results of the Aging Males' Symptoms (AMS) questionnaire for aging males, and of quality of life (QOL) questionnaire SF-12 and cardiovascular risk factors.1,927 men aged 55-85 years were interviewed by 56 general practitioners. During the interview the men were asked to fill in the AMS scale and the QOL questionnaire SF-12.Of 1,927 men 1,806 men filled correctly the AMS questionnaire. The mean SF-12 mental index was respectively 55.9 in men with a total AMS score indicating no impairment, 50.9 mild, 42.8 moderate, and 32.8 severe impairment. The corresponding values for the physical index were 51.2, 46.7, 40.8 and 32.3. A history of diabetes was associated with an increased risk of reporting moderate/severe impairment: in relation to the total AMS score the odds ratio, (OR), of moderate/severe impairment in comparison with no impairment was 1.6 (95%CI 1.2-2.1). A history of myocardial infarction and hypertension increased the risk (respectively OR 1.4 (95%CI 1.1-18) and 1.7 (95%CI 1.2-2.4)).This study shows that higher AMS scores are associated with lower SF-12 indices and suggests that elevated values of the AMS score are associated with cardiovascular risk factors or diseases.
Published: 2008

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