Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open‐Label, Randomized, Bayesian Noninferiority Trial

Funder: Lauren Currie Twilight FoundationFunder: Great Ormond Street Hospital Charity; Id: http://dx.doi.org/10.13039/501100001279Funder: Vasculitis UK; Id: http://dx.doi.org/10.13039/100010876Objective: Cyclophosphamide (CYC) is used in clinical practice off‐label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). Methods: This was an international, open‐label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. Results: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality‐of‐life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). Conclusion: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health‐related quality of life than CYC treatment

Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open-Label, Randomized, Bayesian Noninferiority Trial.

OBJECTIVE: Cyclophosphamide (CYC) is used in clinical practice off-label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). METHODS: This was an international, open-label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. RESULTS: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). CONCLUSION: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health-related quality of life than CYC treatment

The scientific payload on-board the HERMES-TP and HERMES-SP CubeSat missions

none103siHERMES (High Energy Rapid Modular Ensemble of Satellites) Technological and Scientific pathfinder is a space borne mission based on a LEO constellation of nano-satellites. The 3U CubeSat buses host new miniaturized detectors to probe the temporal emission of bright high-energy transients such as Gamma-Ray Bursts (GRBs). Fast transient localization, in a field of view of several steradians and with arcmin-level accuracy, is gained by comparing time delays among the same event detection epochs occurred on at least 3 nano-satellites. With a launch date in 2022, HERMES transient monitoring represents a keystone capability to complement the next generation of gravitational wave experiments. In this paper we will illustrate the HERMES payload design, highlighting the technical solutions adopted to allow a wide-energy-band and sensitive X-ray and gamma-ray detector to be accommodated in a CubeSat 1U volume together with its complete control electronics and data handling system.noneEvangelista, Yuri; Fiore, Fabrizio; Fuschino, Fabio; Campana, Riccardo; Ceraudo, Francesco; Demenev, Evgeny; Guzman, Alejandro; Labanti, Claudio; La Rosa, Giovanni; Fiorini, Mauro; Gandola, Massimo; Grassi, Marco; Mele, Filippo; Morgante, Gianluca; Nogara, Paolo; Piazzolla, Raffaele; Pliego Caballero, Samuel; Rashevskaya, Irina; Russo, Francesco; Sciarrone, Giulia; Sottile, Giuseppe; Milankovich, Dorottya; Pál, András; Ambrosino, Filippo; Auricchio, Natalia; Barbera, Marco; Bellutti, Pierluigi; Bertuccio, Giuseppe; Borghi, Giacomo; Cao, Jiewei; Chen, Tianxiang; Dilillo, Giuseppe; Feroci, Marco; Ficorella, Francesco; Lo Cicero, Ugo; Malcovati, Piero; Morbidini, Alfredo; Pauletta, Giovanni; Picciotto, Antonino; Rachevski, Alexandre; Santangelo, Andrea; Tenzer, Chistoph; Vacchi, Andrea; Wang, Lingjun; Xu, Yupeng; Zampa, Gianluigi; Zampa, Nicola; Zorzi, Nicola; Burderi, Luciano; Lavagna, Michèle; Bertacin, Roberto; Lunghi, Paolo; Monge, Angel; Negri, Barbara; Pirrotta, Simone; Puccetti, Simonetta; Sanna, Andrea; Amarilli, Fabrizio; Amelino-Camelia, Giovanni; Bechini, Michele; Citossi, Marco; Colagrossi, Andrea; Curzel, Serena; Della Casa, Giovanni; Cinelli, Marco; Del Santo, Melania; Di Salvo, Tiziana; Feruglio, Chiara; Ferrandi, Fabrizio; Fiorito, Michele; Gacnik, Dejan; Galgóczi, Gabor; Gambino, Angelo Francesco; Ghirlanda, Giancarlo; Gomboc, Andreja; Karlica, Mile; Efremov, Pavel; Kostic, Uros; Clerici, Aurora; Lopez Fernandez, Borja; Maselli, Alessandro; Nava, Lara; Ohno, Masanori; Ottolina, Daniele; Pasquale, Andrea; Perri, Matteo; Piccinin, Margherita; Prinetto, Jacopo; Riggio, Alessandro; Ripa, Jakub; Papitto, Alessandro; Piranomonte, Silvia; Scala, Francesca; Selcan, David; Silvestrini, Stefano; Rotovnik, Tomaz; Virgilli, Enrico; Troisi, Ivan; Werner, Norbert; Zanotti, Giovanni; Anitra, Alessio; Manca, Arianna; Clerici, AuroraEvangelista, Yuri; Fiore, Fabrizio; Fuschino, Fabio; Campana, Riccardo; Ceraudo, Francesco; Demenev, Evgeny; Guzman, Alejandro; Labanti, Claudio; La Rosa, Giovanni; Fiorini, Mauro; Gandola, Massimo; Grassi, Marco; Mele, Filippo; Morgante, Gianluca; Nogara, Paolo; Piazzolla, Raffaele; Pliego Caballero, Samuel; Rashevskaya, Irina; Russo, Francesco; Sciarrone, Giulia; Sottile, Giuseppe; Milankovich, Dorottya; Pál, András; Ambrosino, Filippo; Auricchio, Natalia; Barbera, Marco; Bellutti, Pierluigi; Bertuccio, Giuseppe; Borghi, Giacomo; Cao, Jiewei; Chen, Tianxiang; Dilillo, Giuseppe; Feroci, Marco; Ficorella, Francesco; Lo Cicero, Ugo; Malcovati, Piero; Morbidini, Alfredo; Pauletta, Giovanni; Picciotto, Antonino; Rachevski, Alexandre; Santangelo, Andrea; Tenzer, Chistoph; Vacchi, Andrea; Wang, Lingjun; Xu, Yupeng; Zampa, Gianluigi; Zampa, Nicola; Zorzi, Nicola; Burderi, Luciano; Lavagna, Michèle; Bertacin, Roberto; Lunghi, Paolo; Monge, Angel; Negri, Barbara; Pirrotta, Simone; Puccetti, Simonetta; Sanna, Andrea; Amarilli, Fabrizio; Amelino-Camelia, Giovanni; Bechini, Michele; Citossi, Marco; Colagrossi, Andrea; Curzel, Serena; Della Casa, Giovanni; Cinelli, Marco; Del Santo, Melania; Di Salvo, Tiziana; Feruglio, Chiara; Ferrandi, Fabrizio; Fiorito, Michele; Gacnik, Dejan; Galgóczi, Gabor; Gambino, Angelo Francesco; Ghirlanda, Giancarlo; Gomboc, Andreja; Karlica, Mile; Efremov, Pavel; Kostic, Uros; Clerici, Aurora; Lopez Fernandez, Borja; Maselli, Alessandro; Nava, Lara; Ohno, Masanori; Ottolina, Daniele; Pasquale, Andrea; Perri, Matteo; Piccinin, Margherita; Prinetto, Jacopo; Riggio, Alessandro; Ripa, Jakub; Papitto, Alessandro; Piranomonte, Silvia; Scala, Francesca; Selcan, David; Silvestrini, Stefano; Rotovnik, Tomaz; Virgilli, Enrico; Troisi, Ivan; Werner, Norbert; Zanotti, Giovanni; Anitra, Alessio; Manca, Arianna; Clerici, Auror

The HERMES-technologic and scientific pathfinder

HERMES-TP/SP (High Energy Rapid Modular Ensemble of Satellites Technologic and Scientific Pathfinder) is a constellation of six 3U nano-satellites hosting simple but innovative X-ray detectors, characterized by a large energy band and excellent temporal resolution, and thus optimized for the monitoring of Cosmic High Energy transients such as Gamma Ray Bursts and the electromagnetic counterparts of Gravitational Wave Events, and for the determination of their positions. The projects are funded by the Italian Ministry of University and Research and by the Italian Space Agency, and by the European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No. 821896. HERMES-TP/SP is an in-orbit demonstration, that should be tested starting from 2022. It is intrinsically a modular experiment that can be naturally expanded to provide a global, sensitive all sky monitor for high-energy transients

Timing techniques applied to distributed modular high-energy astronomy: the H.E.R.M.E.S. project

The association of GW170817 with GRB170817A proved that electromagnetic counterparts of gravitational wave events are the key to deeply understand the physics of NS-NS merges. Upgrades of the existing GW antennas and the construction of new ones will allow to increase sensitivity down to several hundred Mpc vastly increasing the number of possible electromagnetic counterparts. Monitoring of the hard X-ray/soft gamma-ray sky with good localisation capabilities will help to effectively tackle this problem allowing to fully exploit multi-messenger astronomy. However, building a high energy all-sky monitor with large collective area might be particularly challenging due to the need to place the detectors onboard satellites of limited size. Distributed astronomy is a simple and cheap solution to overcome this difficulty. Here we discuss in detail dedicated timing techniques that allow to precisely locate an astronomical event in the sky taking advantage of the spatial distribution of a swarm of detectors orbiting Earth

GrailQuest and HERMES: hunting for gravitational wave electromagnetic counterparts and probing space-time quantum foam

106nonenoneBurderi, Luciano; Di Salvo, Tiziana; Riggio, Alessandro; Gambino, Angelo Francesco; Sanna, Andrea; Fiore, Fabrizio; Amarilli, Fabrizio; Amati, Lorenzo; Ambrosino, Filippo; Amelino-Camelia, Giovanni; Anitra, Alessio; Barbera, Marco; Bechini, Michele; Bellutti, Paolo; Bertaccin, Roberto; Bertuccio, Giuseppe; Campana, Riccardo; Cao, Jiewei; Capozziello, Salvatore; Ceraudo, Francesco; Chen, Tianxiang; Cinelli, Marco; Citossi, Marco; Clerici, Aurora; Colagrossi, Andrea; Costa, Enrico; Curzel, Serena; De Laurentis, Mariafelicia; Della Casa, Giovanni; Della Valle, Massimo; Demenev, Evgeny; Del Santo, Melania; Dilillo, Giuseppe; Efremov, Pavel; Evangelista, Yuri; Feroci, Marco; Ferruglio, Chiara; Ferrandi, Fabrizio; Fiorini, Mauro; Fiorito, Michele; Frontera, Filippo; Fuschino, Fabio; Gacnik, Dejan; Galgoczi, Gabor; Gao, Na; Gandola, Massimo; Ghirlanda, Giancarlo; Gamboc, Andreja; Grassi, Marco; Guidorzi, Cristiano; Guzman, Alejandro; Iaria, Rosario; Karlica, Mile; Kostic, Uros; Labanti, Claudio; La Rosa, Giovanni; Lo Cicero, Ugo; Lopez Fernandez, Borja; Lunghi, Paolo; Malcovati, Piero; Maselli, Alessandro; Manca, Arianna; Mele, Filippo; Milankovich, Dorottya; Monge, Angel; Morgante, Gianluca; Nava, Lara; Negri, Barbara; Nogara, Paolo; Ohno, Masanori; Ottolina, Daniele; Pasquale, Andrea; Pal, Andras; Perri, Matteo; Piccinin, Margherita; Piazzolla, Raffaele; Pirrotta, Simone; Pliego-Caballero, Samuel; Prinetto, Jacopo; Pucacco, Giuseppe; Puccetti, Simonetta; Rapisarda, Massimo; Rashevskaya, Irina; Rashevsky, Alexander; Ripa, Jakub; Russo, Francesco; Papitto, Alessandro; Piranomonte, Silvia; Santangelo, Andrea; Scala, Francesca; Sciarrone, Giulia; Selcan, David; Silvestrini, Stefano; Sottile, Giuseppe; Rotovnik, Tomaz; Tenzer, Christoph; Troisi, Ivan; Vacchi, Andrea; Virgilli, Enrico; Werner, Norbert; Wang, Lingjun; Xu, Yupeng; Zampa, Gianluigi; Zampa, Nicola; Zane, Silvia; Zanotti, GiovanniBurderi, Luciano; Di Salvo, Tiziana; Riggio, Alessandro; Gambino, Angelo Francesco; Sanna, Andrea; Fiore, Fabrizio; Amarilli, Fabrizio; Amati, Lorenzo; Ambrosino, Filippo; Amelino-Camelia, Giovanni; Anitra, Alessio; Barbera, Marco; Bechini, Michele; Bellutti, Paolo; Bertaccin, Roberto; Bertuccio, Giuseppe; Campana, Riccardo; Cao, Jiewei; Capozziello, Salvatore; Ceraudo, Francesco; Chen, Tianxiang; Cinelli, Marco; Citossi, Marco; Clerici, Aurora; Colagrossi, Andrea; Costa, Enrico; Curzel, Serena; De Laurentis, Mariafelicia; Della Casa, Giovanni; Della Valle, Massimo; Demenev, Evgeny; Del Santo, Melania; Dilillo, Giuseppe; Efremov, Pavel; Evangelista, Yuri; Feroci, Marco; Ferruglio, Chiara; Ferrandi, Fabrizio; Fiorini, Mauro; Fiorito, Michele; Frontera, Filippo; Fuschino, Fabio; Gacnik, Dejan; Galgoczi, Gabor; Gao, Na; Gandola, Massimo; Ghirlanda, Giancarlo; Gamboc, Andreja; Grassi, Marco; Guidorzi, Cristiano; Guzman, Alejandro; Iaria, Rosario; Karlica, Mile; Kostic, Uros; Labanti, Claudio; La Rosa, Giovanni; Lo Cicero, Ugo; Lopez Fernandez, Borja; Lunghi, Paolo; Malcovati, Piero; Maselli, Alessandro; Manca, Arianna; Mele, Filippo; Milankovich, Dorottya; Monge, Angel; Morgante, Gianluca; Nava, Lara; Negri, Barbara; Nogara, Paolo; Ohno, Masanori; Ottolina, Daniele; Pasquale, Andrea; Pal, Andras; Perri, Matteo; Piccinin, Margherita; Piazzolla, Raffaele; Pirrotta, Simone; Pliego-Caballero, Samuel; Prinetto, Jacopo; Pucacco, Giuseppe; Puccetti, Simonetta; Rapisarda, Massimo; Rashevskaya, Irina; Rashevsky, Alexander; Ripa, Jakub; Russo, Francesco; Papitto, Alessandro; Piranomonte, Silvia; Santangelo, Andrea; Scala, Francesca; Sciarrone, Giulia; Selcan, David; Silvestrini, Stefano; Sottile, Giuseppe; Rotovnik, Tomaz; Tenzer, Christoph; Troisi, Ivan; Vacchi, Andrea; Virgilli, Enrico; Werner, Norbert; Wang, Lingjun; Xu, Yupeng; Zampa, Gianluigi; Zampa, Nicola; Zane, Silvia; Zanotti, Giovann

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)