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1. Optimization of Long-Haul C+L+S Systems by means of a Closed Form EGN Model

Author

Jiang, Y., Sarkis, J., Nespola, A., Forghieri, F., Piciaccia, S., Tanzi, A., Zefreh, M. Ranjbar, and Poggiolini, P.

Subjects
Electrical Engineering and Systems Science - Signal Processing
Abstract

We investigate C+L+S long-haul systems using a closed-form GN/EGN non-linearity model. We perform accurate launch power and Raman pump optimization. We show a potential 4x throughput increase over legacy C-band systems in 1000 km links, using moderate S-only Raman amplification. We simultaneously achieve extra-flat GSNR, within +/-0.5 dB across the whole C+L+S spectrum., Comment: The paper is identical to a manuscript submitted to PTL in June 2024, except this arXiv version has been updated in the references. Ref. [8] and [10] are about CFM6 and its experimental validation

Published
2024

2. Experimental Test of a Closed-Form EGN Model Over C+L Bands

Author

Jiang, Y., Nespola, A., Straullu, S., Forghieri, F., Piciaccia, S., Tanzi, A., Zefreh, M. Ranjbar, Bosco, G., and Poggiolini, P.

Abstract

This paper focuses on a closed-form ultra-wide-band solution of the GN and EGN model integrals (CFM, for closed form model), collaboratively developed by CISCO and Politecnico di Torino. The version presented here is capable of handling the frequency-dependence of all main system and fiber parameters and accounts accurately for Interchannel Stimulated Raman Scattering (ISRS). In the paper, we first describe the CFM in detail and then we present a validation experiment carried out over a 5-span 128-channel C+L transmission line over SMF. The experiment was designed to explore transmission scenarios ranging from quasi-linear to deeply non-linear, with significant ISRS. We describe the thorough characterization of the link and the careful instrumentation of the set-up, necessary to minimize all errors that might compromise the significance of the measurements. The results are extensively discussed and show a good match between the CFM predictions and the measured performance. The CFM provides a closed-form solution of the GN and EGN model integrals, but other steps of system performance assessment are not closed-form. However, since GN/EGN integrals are by far the most computationally heavy element of the calculation, the overall speed-up granted by using the CFM is quite significant, about four orders of magnitude. The real-time system performance assessment capability thus achieved makes it possible to perform physical-layer-aware numerical optimization of system and link parameters, a critical aspect in multi-band and ultra-wide-band optical networks. Overall, we believe that both the speed and the reliability of the CFM make it a valuable tool with significant potential for practical application in the field.

Published
2025
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3. A Simple and Accurate Closed-Form EGN Model Formula

Author

Poggiolini, P., Jiang, Y., Carena, A., and Forghieri, F.

Subjects
Physics - Optics
Abstract

The GN model of non-linear fiber propagation has been shown to overestimate the variance of non-linearity due to the signal Gaussianity approximation, leading to maximum reach predictions for typical optical systems which may be pessimistic by about 5% to 15%, depending on fiber type and system set-up. Various models have been proposed which improve over the GN model accuracy. One of them is the EGN model, which completely removes the Gaussianity approximation from all non-linear interference (NLI) components. The EGN model is, however, substantially more complex than the GN model. Recently, we proposed a simple closed-form formula which permits to approximate the EGN model, starting from the GN. It was however limited to all-identical, equispaced channels, and did not correct single-channel NLI (also called SCI). In this follow-up contribution, we propose an improved version which both allows to address non-identical channels and corrects the SCI contribution as well. Extensive simulative testing shows the new formula to be asymptotically very accurate, for sufficiently large number of spans. This is a preliminary document which will be followed by a journal submission., Comment: arXiv admin note: substantial text overlap with arXiv:1402.3528

Published
2015

4. Electronic Dispersion Pre-Compensation in PM-QPSK Systems over Mixed-Fiber Links

Author

Carena, A., Jiang, Y., Poggiolini, P., Bosco, G., Curri, V., and Forghieri, F.

Subjects
Physics - Optics
Abstract

Dispersion pre-compensation is shown to potentially lead to a substantial non-linearity reduction in PM-QPSK links that use a mixture of high and low dispersion fibers. However, the much larger PAPR of the pre-compensated signal poses challenging requirements on the transmitter., Comment: This paper was accepted at the ECOC 2014 conference

Published
2014

5. On the Impact of Non-Linear Phase-Noise on the Assessment of Long-Haul Uncompensated Coherent Systems Performance

Author

Jiang, Y., Carena, A., Poggiolini, P., and Forghieri, F.

Subjects
Physics - Optics
Abstract

We accurately characterize nonlinear phase noise in uncompensated coherent optical systems. We find that, though present, its impact on system performance is typically negligible in a wide range of practical system scenarios., Comment: This paper has been accepted at the ECOC 2014 conference

Published
2014

6. Impact of Low-OSNR Operation on the Performance of Advanced Coherent Optical Transmission Systems

Author

Poggiolini, P., Carena, A., Jiang, Y., Bosco, G., Curri, V., and Forghieri, F.

Subjects
Physics - Optics
Abstract

We find evidence that low-OSNR operation causes substantial penalty on system maximum reach due to non-linearity generated by ASE noise and due to signal-power conversion into non-linear noise. Neglecting these effects may lead to a quite substantial performance prediction error., Comment: A prior version of this paper has been accepted at the ECOC 2014 conference. This version contains some important corrections and updates, with respect to the ECOC 2014 paper. Also, the prior pblished arXiv version had a font problem in the pdf file, so that some brackets would not show up in formulas. This new version is identical, except that it fixes the font problem

Published
2014

7. A Simple and Effective Closed-Form GN-Model Correction Formula Accounting for Signal Non-Gaussian Distribution

Author

Poggiolini, P., Bosco, G., Carena, A., Curri, V., Jiang, Y., and Forghieri, F.

Subjects
Physics - Optics
Abstract

The GN model of non-linear fiber propagation has been shown to overestimate the variance of non-linearity due to the signal Gaussianity approximation, leading to maximum reach predictions for realistic optical systems which may be pessimistic by about 5% to 15%, depending on fiber type and system set-up. Analytical corrections have been proposed, which however substantially increase the model complexity. In this paper we provide a simple closed-form GN model correction formula, derived from the EGN model, which we show to be quite effective in correcting for the GN model tendency to overestimate non-linearity. The formula also permits to clearly identify the correction dependence on key system parameters, such as span length and loss., Comment: This paper has been accepted for publication in the IEEE Journal of Lightwave Technology

Published
2014
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8. On the Accuracy of the GN-Model and on Analytical Correction Terms to Improve It

Author

Carena, A., Bosco, G., Curri, V., Jiang, Y., Poggiolini, P., and Forghieri, F.

Subjects
Physics - Optics
Abstract

The GN-model has been proposed as an approximate but sufficiently accurate tool for predicting uncompensated optical coherent transmission system performance, in realistic scenarios. For this specific use, the GN-model has enjoyed substantial validation, both simulative and experimental. Recently, however, it has been pointed out that its predictions, when used to obtain a detailed picture of non-linear interference (NLI) noise accumulation along a link, may be affected by a substantial NLI overestimation error, especially in the first spans of the link. In this paper we analyze in detail the GN-model errors. We discuss recently proposed formulas for correcting such errors and show that they neglect several contributions to NLI, so that they may substantially underestimate NLI in specific situations, especially over low-dispersion fibers. We derive a complete set of formulas accounting for all single, cross, and multi-channel effects, this set constitutes what we have called the enhanced GN-model (EGN-model). We extensively validate the EGN model by comparison with accurate simulations in several different system scenarios. The overall EGN model accuracy is found to be very good when assessing detailed span-by-span NLI accumulation and excellent when estimating realistic system maximum reach. The computational complexity vs. accuracy trade-offs of the various versions of the GN and EGN models are extensively discussed., Comment: This paper has been accepted for publication on OSA Optics Express, with the title: "The EGN model of nonlinear fiber propagation"

Published
2014

9. Ultra-Long-Haul WDM PM-16QAM Transmission in a Reduced Inter-Modal Interference NANF

Author

Nespola, A, primary, Sandoghchi, S R, additional, Hooper, L, additional, Alonso, M, additional, Bradley, T D, additional, Sakr, H, additional, Jasion, G T, additional, Fokoua, E Numkam, additional, Straullu, S, additional, Bosco, G, additional, Carena, A, additional, Jiang, Y, additional, Brusin, A M Rosa, additional, Chen, Y, additional, Hayes, J R, additional, Forghieri, F, additional, Richardson, D J, additional, Poletti, F, additional, and Poggiolini, P, additional

Published
2023
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11. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study

Author

Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, Foa, R, Cerrano M., Bonifacio M., Olivi M., Curti A., Malagola M., Dargenio M., Scattolin A. M., Papayannidis C., Forghieri F., Gurrieri C., Tanasi I., Zappasodi P., Starza R. L., Fracchiolla N. S., Chiusolo P., Giaccone L., Del Principe M. I., Giglio F., Defina M., Favre C., Rizzari C., Castella B., Pizzolo G., Ferrara F., Chiaretti S., Foa R., Cerrano, M, Bonifacio, M, Olivi, M, Curti, A, Malagola, M, Dargenio, M, Scattolin, A, Papayannidis, C, Forghieri, F, Gurrieri, C, Tanasi, I, Zappasodi, P, Starza, R, Fracchiolla, N, Chiusolo, P, Giaccone, L, Del Principe, M, Giglio, F, Defina, M, Favre, C, Rizzari, C, Castella, B, Pizzolo, G, Ferrara, F, Chiaretti, S, Foa, R, Cerrano M., Bonifacio M., Olivi M., Curti A., Malagola M., Dargenio M., Scattolin A. M., Papayannidis C., Forghieri F., Gurrieri C., Tanasi I., Zappasodi P., Starza R. L., Fracchiolla N. S., Chiusolo P., Giaccone L., Del Principe M. I., Giglio F., Defina M., Favre C., Rizzari C., Castella B., Pizzolo G., Ferrara F., Chiaretti S., and Foa R.

Published
2022

12. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia–like or acute lymphoblastic leukemia–like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study

Author

Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Lazzarotto, D., Tanasi, I., Vitale, A., Piccini, M., Dargenio, M., Giglio, F., Forghieri, F., Fracchiolla, N., Cerrano, M., Todisco, E., Papayannidis, C., Leoncin, M., Defina, M., Guolo, F., Pasciolla, C., Delia, M., Chiusolo, Patrizia, Mule, A., Candoni, A., Bonifacio, M., Pizzolo, G., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment.

Published
2023

16. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, Amadori S, Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, Amadori, S, Voso MT, Cucci R, Messina M, Santoro A, Divona M, Albano F, Ottaviani E, Bertorelle R, Guerrasio A, Gottardi E, Izzo B, Tarantini G, Scardocci A, Siragusa S, Forghieri F, Cairoli R, Cambo B, Vallisa D, Venditti A, Ferrara F, Mannina D, Cilloni D, La SalaE, Piciocchi A, Falini B, Pane F, Saglio G, Vignetti M, and Amadori S

Published
2021

17. P1709: FERTILITY PRESERVATION FOR YOUNG ADULT ACUTE LYMPHOBLASTIC LEUKEMIAS IN ITALY: A CAMPUS ALL SURVEY.

Author

Giglio, F., primary, Bruno, A., additional, Dargenio, M., additional, Cerrano, M., additional, Del Principe, M. I., additional, Forghieri, F., additional, Fumagalli, M., additional, Guolo, F., additional, Imovilli, A., additional, Lunghi, M., additional, Mazzone, C., additional, Papayannidis, C., additional, Pasciolla, C., additional, Trappolini, S., additional, Lazzarotto, D., additional, Bonifacio, M., additional, Candoni, A., additional, Ciceri, F., additional, Pizzolo, G., additional, Vitale, A., additional, and Foà, R., additional

Published
2022
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18. P357: MULTICENTER RETROSPECTIVE ANALYSIS OF CLINICAL OUTCOME OF ADULT PATIENS WITH MIXED-PHENOTYPE ACUTE LEUKEMIA (MPAL) DIAGNOSED AND TREATED IN THE LAST TEN YEARS. A CAMPUS-ALL STUDY.

Author

Lazzarotto, D., primary, Tanasi, I., additional, Vitale, A., additional, Piccini, M., additional, Dargenio, M., additional, Giglio, F., additional, Forghieri, F., additional, Fracchiolla, N., additional, Cerrano, M., additional, Todisco, E., additional, Papayannidis, C., additional, Leoncin, M., additional, Defina, M., additional, Guolo, F., additional, Pasciolla, C., additional, Delia, M., additional, Chiusolo, P., additional, Mulè, A., additional, Candoni, A., additional, Bonifacio, M., additional, Pizzolo, G., additional, and Foà, R., additional

Published
2022
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19. P1708: PREGNANCIES IN YOUNG ADULTS WITH A HISTORY OF ACUTE LYMPHOBLASTIC LEUKEMIA IN ITALY. A CAMPUS ALL SURVEY.

Author

Giglio, F., primary, Bruno, A., additional, Papayannidis, C., additional, Dargenio, M., additional, Cerrano, M., additional, Forghieri, F., additional, Fumagalli, M., additional, Lunghi, M., additional, Annunziata, M., additional, Bonifacio, M., additional, Ferrara, F., additional, Ciceri, F., additional, Pizzolo, G., additional, Vitale, A., additional, and Foà, R., additional

Published
2022
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20. P307: DEL(17)(Q11) IS TYPICAL MARKER OF IMMATURE T-ALL OF ADULTS, WITH NF1, UTP6, AND SUZ12 HAPLOINSUFFICIENCY, GENOME INSTABILITY, AND GENE DOWNREGULATION

Author

Bardelli, V., primary, Pierini, V., additional, Arniani, S., additional, Mvridou, E., additional, Matteucci, C., additional, Lema Fernandez, A. G., additional, Moretti, M., additional, Elia, L., additional, Giglio, F., additional, Forghieri, F., additional, Cerrano, M., additional, Fracchiolla, N., additional, Delia, M., additional, Sica, S., additional, Mecucci, C., additional, and La Starza, R., additional

Published
2022
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21. COVID-19 infection in acute lymphoblastic leukemia over 15 months of the pandemic. A Campus ALL report

Author

Chiaretti, S., Bonifacio, M., Agrippino, R., Giglio, F., Annunziata, M., Curti, A., Del Principe, M. I., Salutari, P., Sciume, M., Delia, M., Armenio, M., Mancini, V., Mule, A., Grimaldi, F., Rege-Cambrin, G., Santoro, L., Lussana, F., Chiusolo, Patrizia, Pasciolla, C., Scattolin, A. M., Cerrano, M., Ciccone, M., Defina, M., Forghieri, F., Mazzone, C., Piccini, M., Ferrara, F., Pizzolo, G., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Chiaretti, S., Bonifacio, M., Agrippino, R., Giglio, F., Annunziata, M., Curti, A., Del Principe, M. I., Salutari, P., Sciume, M., Delia, M., Armenio, M., Mancini, V., Mule, A., Grimaldi, F., Rege-Cambrin, G., Santoro, L., Lussana, F., Chiusolo, Patrizia, Pasciolla, C., Scattolin, A. M., Cerrano, M., Ciccone, M., Defina, M., Forghieri, F., Mazzone, C., Piccini, M., Ferrara, F., Pizzolo, G., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

N/A

Published
2022

22. Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study

Author

Cerrano, M., Bonifacio, M., Olivi, M., Curti, A., Malagola, M., Dargenio, M., Scattolin, A. M., Papayannidis, C., Forghieri, F., Gurrieri, C., Tanasi, I., Zappasodi, P., Starza, R. L., Fracchiolla, N. S., Chiusolo, Patrizia, Giaccone, L., Del Principe, M. I., Giglio, F., Defina, M., Favre, C., Rizzari, C., Castella, B., Pizzolo, G., Ferrara, F., Chiaretti, S., Foa, R., Chiusolo P. (ORCID:0000-0002-1355-1587), Cerrano, M., Bonifacio, M., Olivi, M., Curti, A., Malagola, M., Dargenio, M., Scattolin, A. M., Papayannidis, C., Forghieri, F., Gurrieri, C., Tanasi, I., Zappasodi, P., Starza, R. L., Fracchiolla, N. S., Chiusolo, Patrizia, Giaccone, L., Del Principe, M. I., Giglio, F., Defina, M., Favre, C., Rizzari, C., Castella, B., Pizzolo, G., Ferrara, F., Chiaretti, S., Foa, R., and Chiusolo P. (ORCID:0000-0002-1355-1587)

Abstract

n/a

Published
2022

25. LABNET AML: AN EFFICIENT NETWORK THAT CONNECTS HEMATOLOGY CENTERS AND LABORATORIES FOR A HIGH-LEVEL DIAGNOSTIC/PROGNOSTIC WORKUP OF AML

Author

Voso, M. T., Cucci, R., Messina, M., Santoro, A., Divona, M., Albano, F., Ottaviani, E., Roberta Bertorelle, Guerrasio, A., Gottardi, E., Izzo, B., Tarantini, G., Scardocci, A., Siragusa, S., Forghieri, F., Cairoli, R., Cambo, B., Vallisa, D., Venditti, A., Ferrara, F., Mannina, D., Cilloni, D., La Sala, E., Piciocchi, A., Falini, B., Pane, F., Saglio, G., Vignetti, M., Amadori, S., Voso, M, Cucci, R, Messina, M, Santoro, A, Divona, M, Albano, F, Ottaviani, E, Bertorelle, R, Guerrasio, A, Gottardi, E, Izzo, B, Tarantini, G, Scardocci, A, Siragusa, S, Forghieri, F, Cairoli, R, Cambo, B, Vallisa, D, Venditti, A, Ferrara, F, Mannina, D, Cilloni, D, La, S, Piciocchi, A, Falini, B, Pane, F, Saglio, G, Vignetti, M, and Amadori, S

Subjects
Hematology
Published
2021

28. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases

Author

Candoni A, Klimko N, Busca A, Di Blasi R, Shadrivova O, Cesaro S, Zannier ME, Verga L, Forghieri F, Calore E, Nadali G, Simonetti E, Muggeo P, Quinto AM, Castagnola C, Cellini M, Del Principe MI, Fracchiolla N, Melillo L, Piedimonte M, Zama D, Farina F, Giusti D, Mosna F, Capelli D, Delia M, Picardi M, Decembrino N, Perruccio K, Vallero S, Aversa F, Fanin R, Pagano L, SEIFEM Group (Epidemiological Surveillance of Infections in Haematological Diseases), Candoni, A., Klimko, N., Busca, A., Di Blasi, R., Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, Aldo, Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, L., Candoni A, Klimko N, Busca A, Di Blasi R, Shadrivova O, Cesaro S, Zannier ME, Verga L, Forghieri F, Calore E, Nadali G, Simonetti E, Muggeo P, Quinto AM, Castagnola C, Cellini M, Del Principe MI, Fracchiolla N, Melillo L, Piedimonte M, Zama D, Farina F, Giusti D, Mosna F, Capelli D, Delia M, Picardi M, Decembrino N, Perruccio K, Vallero S, Aversa F, Fanin R, Pagano L, and SEIFEM Group (Epidemiological Surveillance of Infections in Haematological Diseases)

Subjects
0301 basic medicine, Male, Antifungal Agents, haematological disease, Aspergillosis, fungal CNS infectious, haematological diseases, leukaemia, neurologic complications, Zygomicosis, 030207 dermatology & venereal diseases, 0302 clinical medicine, Central Nervous System Fungal Infections, Epidemiology, Paranasal Sinuses, Sinusitis, Child, Adolescent, Adult, Aged, Cerebrospinal Fluid, Child, Preschool, Epidemiologic Studies, Female, Fungi, Hematologic Neoplasms, Humans, Middle Aged, Survival Analysis, Treatment Outcome, Young Adult, Debridement, medicine.diagnostic_test, aspergillosis, fungal cns infectious, zygomicosis, neurologic complication, General Medicine, medicine.anatomical_structure, Infectious Diseases, Cohort, medicine.drug, medicine.medical_specialty, fungal CNS infectiou, Aspergillosi, 030106 microbiology, Dermatology, 03 medical and health sciences, Internal medicine, Biopsy, medicine, Preschool, Invasive fungal infection, central nervous system, onco-haematologic patients, Survival analysis, Voriconazole, business.industry, Zygomicosi, medicine.disease, Paranasal sinuses, 2708, business, Settore MED/15 - Malattie del Sangue
Abstract

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Published
2018

31. Do high MICs predict the outcome in invasive fusariosis?

Author

Nucci, M., Jenks, J., Thompson, G. R., Hoenigl, M., Dos Santos, M. C., Forghieri, F., Rico, J. C., Bonuomo, V., Lopez-Soria, L., Lass-Florl, C., Candoni, A., Garcia-Vidal, C., Cattaneo, C., Buil, J., Rabagliati, R., Roiz, M. P., Gudiol, C., Fracchiolla, N., Campos-Herrero, M. I., Delia, M., Farina, F., Fortun, J., Nadali, G., Sastre, E., Colombo, A. L., Perez Nadales, E., Alastruey-Izquierdo, A., Pagano, Livio, Pagano L. (ORCID:0000-0001-8287-928X), Nucci, M., Jenks, J., Thompson, G. R., Hoenigl, M., Dos Santos, M. C., Forghieri, F., Rico, J. C., Bonuomo, V., Lopez-Soria, L., Lass-Florl, C., Candoni, A., Garcia-Vidal, C., Cattaneo, C., Buil, J., Rabagliati, R., Roiz, M. P., Gudiol, C., Fracchiolla, N., Campos-Herrero, M. I., Delia, M., Farina, F., Fortun, J., Nadali, G., Sastre, E., Colombo, A. L., Perez Nadales, E., Alastruey-Izquierdo, A., Pagano, Livio, and Pagano L. (ORCID:0000-0001-8287-928X)

Abstract

BACKGROUND: Invasive fusariosis (IF) affects mostly severely immunocompromised hosts and is associated with poor outcome. Since Fusarium species exhibit high MICs for most antifungal agents, this could explain the poor prognosis. However, a clear-cut correlation between MIC and outcome has not been established. OBJECTIVE: To evaluate the correlation between MIC and outcome (6 week death rate) in patients with IF. METHODS: We performed a multicentre retrospective study of patients with IF who received treatment and had MIC levels determined by EUCAST or CLSI for the drug(s) used during treatment. We compared the MIC50 and MIC distribution among survivors and patients who died within 6 weeks from the diagnosis of IF. RESULTS: Among 88 patients with IF, 74 had haematological diseases. Primary treatment was monotherapy in 52 patients (voriconazole in 27) and combination therapy in 36 patients (liposomal amphotericin B + voriconazole in 23). The MIC50 and range for the five most frequent agents tested were: voriconazole 8 mg/L (range 0.5-64), amphotericin B 2 mg/L (range 0.25-64), posaconazole 16 mg/L (range 0.5-64), itraconazole 32 mg/L (range 4-64), and isavuconazole 32 mg/L (range 8-64). There was no difference in MIC50 and MIC distribution among survivors and patients who died. By contrast, persistent neutropenia and receipt of corticosteroids were strong predictors of 6 week mortality. CONCLUSIONS: Our study did not show any correlation between MIC and mortality at 6 weeks in patients with IF.

Published
2021

39. Characterization ofFLT3-ITD(mut)acute myeloid leukemia: molecular profiling of leukemic precursor cells

Author

Travaglini, S, Angelini, DF, Alfonso, V, Guerrera, G, Lavorgna, S, Divona, M, Nardozza, AM, Consalvo, MI, Fabiani, E, De Bardi, M, Neri, B, Forghieri, F, Marchesi, F, Paterno, G, Cerretti, R, Barragan, E, Fiori, V, Dominici, S, Del Principe, MI, Venditti, A, Battistini, L, Arcese, W, Lo-Coco, F, Voso, MT, and Ottone, T

Subjects
body regions, psychological phenomena and processes
Abstract

Acute myeloid leukemia (AML) withFLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts forFLT3-ITD-positivity. The aim of this study was to characterize the distribution ofFLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture ofFLT3-ITD(mut)AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients withFLT3-ITD(mut)AML (n = 12). A higherFLT3-ITD(mut)load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/-,CD25-,CD99low/-) (p = 0.0005) and mononuclear cells (MNCs) (p < 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higherFLT3-ITD(mut)burden was also observed in LPCs of AML patients with a smallFLT3-ITD(mut)clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows thatFLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target inFLT3-ITD(mut)AML.

Published
2020

40. Investigating the association between physicians self-efficacy regarding communication skills and risk of 'burnout'

Author

Messerotti, A., Banchelli, F., Ferrari, S., Barbieri, E., Bettelli, F., Bandieri, E., Giusti, D., Catellani, H., Borelli, E., Colaci, E., Pioli, V., Morselli, M., Forghieri, F., Galeazzi, G. M., Marasca, R., Bigi, S., D'Amico, R., Martin, P., Efficace, F., Luppi, M., Potenza, L., Bigi S. (ORCID:0000-0003-0506-6140), Messerotti, A., Banchelli, F., Ferrari, S., Barbieri, E., Bettelli, F., Bandieri, E., Giusti, D., Catellani, H., Borelli, E., Colaci, E., Pioli, V., Morselli, M., Forghieri, F., Galeazzi, G. M., Marasca, R., Bigi, S., D'Amico, R., Martin, P., Efficace, F., Luppi, M., Potenza, L., and Bigi S. (ORCID:0000-0003-0506-6140)

Abstract

Background: Breaking bad news (BBN) may be associated with increasing risk of burnout in practising physicians. However, there is little research on the association between the way bad news is broken and burnout. We investigated the association between physicians' self-efficacy regarding communication to patients and risk of burnout. Methods: We performed a cross-sectional study by proposing an ad-hoc survey exploring attitudes and practice regarding BBN and the Maslach Burnout Inventory - Human Service Survey to 379 physicians from two University Hospitals in Italy. Associations were assessed by multivariable logistic regression models. Results: Two-hundred twenty-six (60%) physicians returned the questionnaires. 76% of physicians acquired communication skills by observing mentors or colleagues, 64% considered BBN as discussing a poor prognosis, 56% reported discussing prognosis as the most difficult task, 38 and 37% did not plan a BBN encounter and considered it stressful. The overall burnout rate was 59%. Considering BBN a stressful task was independently associated with high risk of burnout (OR 3.01; p = 0.013). Planning the encounter (OR = 0.43, p = 0.037), mastering communication skills (OR = 0.19, p = 0.034) and the self-evaluation as good or very good at BBN (OR 0.32; 0.15 to 0.71; p = 0.0) were associated with low risk of burnout. Conclusions: Our findings suggest that some physicians' BBN attitudes and knowledge of conceptual frameworks may influence the risk of burnout and support the notion that increasing knowledge about communication skills may protect clinicians from burnout. Further research is needed in this area.

Published
2020

42. Contributors

Author

Bergano, Neal S., primary, Berthold, Joseph E., additional, Chan, Vincent W.S., additional, Chraplyvy, A.R., additional, Darcie, Thomas E., additional, DiGiovanni, David J., additional, Fan, Chungpeng, additional, Forghieri, F., additional, Frigo, Nicholas J., additional, Gnauck, A.H., additional, Gordon, J.P., additional, Jablonowski, Donald P., additional, Jackson, Kenneth W., additional, Jopson, R.M., additional, Kaminow, Ivan P., additional, Kunz, J.P., additional, Mamyshev, P.Y., additional, Don Mathis, T., additional, Mollenauer, L.F., additional, Nagel, Jonathan, additional, Ogawa, Kinichiro, additional, Park, Yong Kwan, additional, Patel, P.D., additional, Phillips, Mary R., additional, Poole, Craig D., additional, Sano, Eiichi, additional, Santana, Manuel R., additional, Thomas, Phillip M., additional, Tkach, R.W., additional, Tzeng, Liang D., additional, and Yan, Man F., additional

Published
1997
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45. PS1274 EPIDEMIOLOGY AND MANAGEMENT OF LATENT TUBERCULOSIS INFECTION IN ADULT PATIENTS WITH ACUTE LEUKEMIA OR APLASTIC ANEMIA: A RETROSPECTIVE MONOCENTER STUDY

Author

Bettelli, F., primary, Giusti, D., additional, Morselli, M., additional, Paolini, A., additional, Colaci, E., additional, Nasillo, V., additional, Messerotti, A., additional, pioli, V., additional, Arletti, L., additional, Gilioli, A., additional, Celli, M., additional, Donatelli, F., additional, Iotti, S., additional, Catellani, H., additional, Galassi, L., additional, Colasante, C., additional, Vallerini, D., additional, Barozzi, P., additional, Lagreca, I., additional, Maffei, R., additional, Riva, G., additional, Franceschini, E., additional, Codeluppi, M., additional, Mussini, C., additional, Marasca, R., additional, Narni, F., additional, Potenza, L., additional, Luppi, M., additional, and Forghieri, F., additional

Published
2019
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46. S1620 NELARABINE AS SALVAGE THERAPY AND BRIDGE TO ALLOGENEIC STEM CELLS TRANSPLANTATION IN 118 ADULT PATIENTS WITH RELAPSED/REFRACTORY T-ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA. A CAMPUS-ALL, PHASE 4, STUDY.

Author

Candoni, A., primary, Lazzarotto, D., additional, Curti, A., additional, Ferrara, F., additional, Lussana, F., additional, Papayannidis, C., additional, Del Principe, M.I., additional, Bonifacio, M., additional, Mosna, F., additional, Delia, M., additional, Minetto, P., additional, Gottardi, M., additional, Fracchiolla, N., additional, Mancini, V., additional, Forghieri, F., additional, Zappasoldi, P., additional, Cerrano, M., additional, Vitale, A., additional, Audisio, E., additional, Trappolini, S., additional, Romani, C., additional, Defina, M., additional, Imbergamo, S., additional, Ciccone, N., additional, Santoro, L., additional, Cambò, B., additional, Iaccarino, S., additional, Dargenio, M., additional, Aprile, L., additional, Pizzolo, G., additional, and Foà, R., additional

Published
2019
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47. Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases

Author

Candoni, A., Klimko, N., Busca, A., Di Blasi, Roberta, Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, E., Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, Livio, Di Blasi, R., Pagano, L. (ORCID:0000-0001-8287-928X), Candoni, A., Klimko, N., Busca, A., Di Blasi, Roberta, Shadrivova, O., Cesaro, S., Zannier, M. E., Verga, L., Forghieri, F., Calore, E., Nadali, G., Simonetti, E., Muggeo, P., Quinto, A. M., Castagnola, C., Cellini, M., Del Principe, M. I., Fracchiolla, N., Melillo, L., Piedimonte, M., Zama, D., Farina, F., Giusti, D., Mosna, F., Capelli, D., Delia, M., Picardi, M., Decembrino, N., Perruccio, K., Vallero, S., Aversa, F., Fanin, R., Pagano, Livio, Di Blasi, R., and Pagano, L. (ORCID:0000-0001-8287-928X)

Abstract

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due

Published
2019

48. Variability of Voriconazole Trough Levels in Haematological Patients: Influence of Comedications with cytochrome P450(CYP) Inhibitors and/or with CYP Inhibitors plus CYP Inducers

Author

Cojutti, P., Candoni, A., Forghieri, F., Isola, Miriam, Zannier, Maria Elena, Bigliardi, S., Luppi, M., Fanin, Renato, Pea, F., Pea, Federico, Cojutti P., Candoni A., Forghieri F., Isola M., Zannier M.E., Bigliardi S., Luppi M., Fanin R., and Pea F.

Subjects
0301 basic medicine, Male, PHARMACOKINETICS, Antifungal Agents, Pharmacology, Toxicology, GUIDELINES, urologic and male genital diseases, Antineoplastic Agent, Retrospective Studie, Cytochrome P-450 Enzyme Inducers, Cytochrome P-450 Enzyme Inhibitors, Antifungal Agent, Drug Interactions, heterocyclic compounds, Omeprazole, medicine.diagnostic_test, OMEPRAZOLE, General Medicine, respiratory system, Middle Aged, Treatment Outcome, Drug Interaction, Italy, Hematologic Neoplasms, Practice Guidelines as Topic, Female, ASPERGILLOSIS, Drug Monitoring, medicine.drug, Human, Adult, PLASMA-CONCENTRATIONS, Cytochrome P-450 Enzyme Inducer, 030106 microbiology, Antineoplastic Agents, Cytochrome P-450 Enzyme Inhibitor, 03 medical and health sciences, Cmin, INVASIVE FUNGAL-INFECTIONS, STEM-CELL TRANSPLANTATION, PROTON PUMP INHIBITORS, ANTIFUNGAL THERAPY, EFFICACY, medicine, Humans, Invasive Fungal Infection, Hematologic Neoplasm, Retrospective Studies, Pantoprazole, Voriconazole, business.industry, organic chemicals, enzymes and coenzymes (carbohydrates), Therapeutic drug monitoring, Trough level, business, Invasive Fungal Infections
Abstract

Voriconazole plasma exposure greatly varies among haematological patients. The purpose of this study was to identify the magnitude of influence of comedications with CYP inhibitors and/or with CYP inhibitors plus CYP inducers on voriconazole trough level (Cmin). Voriconazole Cmin was retrospectively assessed among haematological patients who underwent therapeutic drug monitoring (TDM). Univariate and multivariate linear mixed-effect regression analyses were performed to identify the independent predictors of normalized Cmin. Of the 83 included patients, 35 had comedications with CYP inhibitors (omeprazole or pantoprazole) and 21 with CYP inhibitors (omeprazole or pantoprazole) plus CYP inducers (methylprednisolone, dexamethasone, phenobarbital, rifampin or carbamazepine). Median Cmin value (n = 199) was 2.4 mg/L with a wide range of distribution (5.5 mg/L (OR: 23.22, 95% CI: 3.01-179.09, p = 0.003). No significant association emerged when CYP inhibitors were coadministered with CYP inducers (OR: 3.53, 95% CI: 0.36-34.95, p = 0.280). The amount of expected Cmin increase was significantly influenced by both the type and the dose of the administered proton pump inhibitor. The study highlights that the benefit from TDM of voriconazole may be maximal in those patients who are cotreated with CYP inhibitors and/or with CYP inhibitors plus CYP inducers, especially when receiving proton pump inhibitors (PPIs) at very high dosages intravenously.

Published
2016

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