Bone and gut microbiota crosstalk: A novel 3D in vitro approach

The present research aimed at shedding light on the interplay between the composition of the human gut microbiota and bone cells

Appendectomy during the COVID-19 pandemic in Italy: a multicenter ambispective cohort study by the Italian Society of Endoscopic Surgery and new technologies (the CRAC study)

Major surgical societies advised using non-operative management of appendicitis and suggested against laparoscopy during the COVID-19 pandemic. The hypothesis is that a significant reduction in the number of emergent appendectomies was observed during the pandemic, restricted to complex cases. The study aimed to analyse emergent surgical appendectomies during pandemic on a national basis and compare it to the same period of the previous year. This is a multicentre, retrospective, observational study investigating the outcomes of patients undergoing emergent appendectomy in March-April 2019 vs March-April 2020. The primary outcome was the number of appendectomies performed, classified according to the American Association for the Surgery of Trauma (AAST) score. Secondary outcomes were the type of surgical technique employed (laparoscopic vs open) and the complication rates. One thousand five hundred forty one patients with acute appendicitis underwent surgery during the two study periods. 1337 (86.8%) patients met the inclusion criteria: 546 (40.8%) patients underwent surgery for acute appendicitis in 2020 and 791 (59.2%) in 2019. According to AAST, patients with complicated appendicitis operated in 2019 were 30.3% vs 39.9% in 2020 (p = 0.001). We observed an increase in the number of post-operative complications in 2020 (15.9%) compared to 2019 (9.6%) (p < 0.001). The following determinants increased the likelihood of complication occurrence: undergoing surgery during 2020 (+ 67%), the increase of a unit in the AAST score (+ 26%), surgery performed > 24 h after admission (+ 58%), open surgery (+ 112%) and conversion to open surgery (+ 166%). In Italian hospitals, in March and April 2020, the number of appendectomies has drastically dropped. During the first pandemic wave, patients undergoing surgery were more frequently affected by more severe appendicitis than the previous year's timeframe and experienced a higher number of complications. Trial registration number and date: Research Registry ID 5789, May 7th, 202

Design e prototipazione di un dispositivo microfluidico per lo studio in vitro delle interazioni tra il microbiota intestinale e i tessuti

Il corpo umano è abitato da un'ampia gamma di microrganismi che vengono indicati collettivamente come microbiota umano. Il microbiota ha un ruolo fondamentale nell’equilibrio tra salute e malattia all’interno dell’omeostasi corporea. Mentre i microbi ottengono un habitat e nutrimento dall'ospite, questi a loro volta aiutano l'ospite regolandone le varie funzioni fisiologiche, inclusa la digestione alimentare, impartendo un'immunità protettiva contro i patogeni e producendo metaboliti. Alterazioni nella composizione del microbiota intestinale, chiamate disbiosi, sono associate e correlate a diverse malattie, che spaziano da disordini gastrointestinali localizzati a malattie neurologiche e del sistema respiratorio. Per comprendere i meccanismi di come una condizione di disbiosi influenzi le diverse patologie si è reso necessario uno studio in vitro del microbiota intestinale. Negli ultimi anni sono stati progettati e utilizzati diversi dispositivi di microfluidica come base per lo studio di queste interazioni riproducendo in maniera più fedele l’interfaccia fisiologica tessuto-microbiota. I dispositivi di microfluidica sono sistemi a perfusione che ospitano una o più tipologie cellulari e mirano a riprodurre strutture, funzioni e aspetti chiave del metabolismo umano di un determinato tessuto o organo nella fisiologia normale e patologica. Alla luce di queste considerazioni, nel presente lavoro di tesi è stata progettata e realizzata una piattaforma microfluidica, interamente stampata in 3D, che permette lo studio del microbiota intestinale attraverso la coltura in vitro. Una soluzione a base di Pluronic F127 è stata utilizzata come inchiostro sacrificale per la realizzazione del circuito microfluidico. Inizialmente è stato realizzato un dializzatore che potesse essere utilizzato durante la coltura batterica; successivamente è stata integrata una camera di coltura al dispositivo utilizzando la stessa tecnica di stampa. Insieme a queste due tipologie di dispositivi è stato realizzato anche un frame esterno per la chiusura ermetica. È stato inoltre, impostato un modello agli elementi finiti per valutare il dispositivo progettato da un punto di vista della dialisi e della fluidodinamica coinvolta. La piattaforma ha previsto anche il design di una camera di anaerobiosi ad hoc con il fine di andare a ricreare l’ambiente necessario per la sopravvivenza e la proliferazione batterica. Questo box sensorizzato inoltre, permetterà il collegamento con una camera di coltura cellulare per analizzare i meccanismi di interazione tra il microbiota intestinale e le cellule di altri tessuti dell’ospite. The human body is inhabited by a wide range of microorganisms that are collectively referred to as the human microbiota. The microbiota plays a key role in the balance between health and disease within the body's homeostasis. While microbes obtain habitat and nourishment from the host, they in turn assist the host by regulating various physiological functions, including food digestion, imparting protective immunity against pathogens, and producing metabolites. Alterations in the composition of the gut microbiota, called dysbiosis, are associated with and related to a variety of diseases, ranging from localized gastrointestinal disorders to neurological and respiratory system diseases. To understand the mechanisms of how a dysbiosis condition affects different diseases, an in vitro study of the gut microbiota has become necessary. In recent years, several microfluidic devices have been designed and used as a basis for the study of these interactions by reproducing more faithfully the physiological tissue-microbiota interface. Microfluidics devices are perfusion systems that host one or more cell types and aim to reproduce key structures, functions and aspects of human metabolism of a given tissue or organ in normal and pathological physiology. In the light of these considerations, in the present thesis work, a microfluidic platform, entirely 3D printed, has been designed and realized to allow the study of the intestinal microbiota through in vitro culture. A Pluronic F127-based solution was used as a sacrificial ink for the realization of the microfluidic circuit. Initially, a dialyzer was made that could be used during bacterial culture; subsequently, a culture chamber was integrated to the device using the same printing technique. Along with these two types of devices, an external frame was also made for hermetic closure. In addition, a finite element model was set up to evaluate the designed device from a dialysis and fluid dynamics involved point of view. The platform has also provided the design of an ad hoc anaerobic chamber in order to recreate the necessary environment for the survival and proliferation of bacteria. This sensorized box will also allow the connection with a cell culture chamber to analyze the mechanisms of interaction between the intestinal microbiota and cells of other tissues of the host

Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study

Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Interpretation Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. Funding Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo

Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

none191norestrictedAscione, Antonio*; De Luca, Massimo; Melazzini, Mario; Montilla, Simona; Trotta, Maria Paola; Petta, Salvatore; Puoti, Massimo; Sangiovanni, Vincenzo; Messina, Vincenzo; Bruno, Savino; Izzi, Antonio; Villa, Erica; Aghemo, Alessio; Zignego, Anna Linda; Orlandini, Alessandra; Fontanella, Luca; Gasbarrini, Antonio; Marzioni, Marco; Giannini, Edoardo G.; Craxì, Antonio; Abbati, Giuseppe; Alberti, Alfredo; Andreone, Pietro; Andreoni, Massimo; Angeli, Paolo; Angelico, Mario; Angarano, Gioacchino; Angrisani, Debora; Antinori, Andrea; Antonini, Cinzia; Avancini, Ivo; Barone, Michele; Bruno, Raffaele; Benedetti, Antonio; Bernabucci, Veronica; Blanc, Pier; Boarini, Chiara; Boffa, Nicola; Boglione, Lucio; Borghi, Vanni; Borgia, Guglielmo; Brancaccio, Giuseppina; Brunetto, Maurizia; Cacciola, Irene; Calabrese, Paolo; Calvaruso, Vincenza; Campagnolo, Davide; Canovari, Benedetta; Caporaso, Nicola; Capra, Franco; Carolo, Giada; Cassola, Giovanni; Castelli, Francesco; Cauda, Roberto; Silberstein, Francesca Ceccherini; Cecere, Roberto; Chessa, Luchino; Chiodera, Alessandro; Chirianni, Antonio; Ciancio, Alessia; Cima, Serena; Coco, Barbara; Colombo, Massimo; Coppola, Nicola; Corti, Giampaolo; Cosco, Lucio; Corradori, Silvia; Cozzolongo, Raffaele; Cristaudo, Antonio; Danieli, Elena; Monforte, Antonella D’Arminio; Monache, Marco delle; Del Poggio, Paolo; de Luca, Andrea; Dentone, Chiara; Di Biagio, Antonio; Di Leo, Alfredo; Di Perri, Giovanni; Di Stefano, Marco; D’Offizi, Giampiero; Donato, Francesca; Durante, Emanuele; Erne, Elke; Fagiuoli, Stefano; Falasca, Katia; Federico, Alessandro; Felder, Martina; Ferrari, Carlo; Gaeta, Giovanni Battista; Ganga, Roberto; Gatti, Pietro; Giacomet, Vania; Giacometti, Andrea; Gianstefani, Alice; Giordani, Maria; Giorgini, Alessia; Grieco, Antonio; Guerra, Michele; Gulminetti, Roberto; Ieluzzi, Donatella; Imparato, Michele; Iodice, Valentina; La Monica, Silvia; Lazzarin, Adriano; Lenzi, Marco; Levrero, Massimo; Lichtner, Myriam; Lionetti, Raffaella; Guercio, Carmela Lo; Madonna, Salvatore; Magnani, Silvia; Maida, Ivana; Marignani, Massimo; Marrone, Aldo; Marsetti, Fabio; Martini, Silvia; Masarone, Mario; Maserati, Renato; Mastroianni, Claudio Maria; Memoli, Massimo; Menzaghi, Barbara; Merli, Manuela; Miele, Luca; Milella, Michele; Mondelli, Mario; Montalbano, Marzia; Monti, Monica; Morelli, Olivia; Morisco, Filomena; Nardone, Gaetano; Novara, Sergio; Onnelli, Giovanna; Onofrio, Mirella; Paganin, Simona; Pani, Luca; Parisi, Maria Rita; Parruti, Giustino; Pasquazzi, Caterina; Pasulo, Luisa; Perno, Carlo Federico; Persico, Marcello; Piai, Guido; Picciotto, Antonino; Pigozzi, Grazielle Marie; Piovesan, Sara; Piras, Maria Chiara; Pirisi, Massimo; Piscaglia, Anna Maria; Ponti, Laura; Potenza, Domenico; Pravadelli, Cecilia; Quartini, Mariano; Quirino, Tiziana; Raimondo, Giovanni; Rapaccini, Gian Ludovico; Rendina, Maria; Rizzardini, Giuliano; Rizzetto, Mario; Rizzo, Salvatore; Romagnoli, Dante; Romano, Antonietta; Rossi, Cristina; Rumi, Maria Grazia; Russello, Maurizio; Russo, Francesca Paolo; Russo, Maria Luisa; Sansonno, Domenico Ettore; Santantonio, Teresa Antonia; Saracco, Giorgio; Schimizzi, Anna Maria; Serviddio, Gaetano; Simeone, Filomena; Solinas, Attilio; Soria, Alessandro; Tabone, Marco; Taliani, Gloria; Tarantino, Giuseppe; Tarquini, Pierluigi; Tavio, Marcello; Termite, Antonio; Teti, Elisabetta; Toniutto, Pierluigi; Torti, Carlo; Tundi, Paolo; Vecchiet, Giacomo; Verucchi, Gabriella; Gentilucci, Umberto Vespasiani; Vinci, Maria; Vullo, Vincenzo; Zolfino, Teresa; Zuin, MassimoAscione, Antonio; De Luca, Massimo; Melazzini, Mario; Montilla, Simona; Trotta, Maria Paola; Petta, Salvatore; Puoti, Massimo; Sangiovanni, Vincenzo; Messina, Vincenzo; Bruno, Savino; Izzi, Antonio; Villa, Erica; Aghemo, Alessio; Zignego, Anna Linda; Orlandini, Alessandra; Fontanella, Luca; Gasbarrini, Antonio; Marzioni, Marco; Giannini, Edoardo G.; Craxì, Antonio; Abbati, Giuseppe; Alberti, Alfredo; Andreone, Pietro; Andreoni, Massimo; Angeli, Paolo; Angelico, Mario; Angarano, Gioacchino; Angrisani, Debora; Antinori, Andrea; Antonini, Cinzia; Avancini, Ivo; Barone, Michele; Bruno, Raffaele; Benedetti, Antonio; Bernabucci, Veronica; Blanc, Pier; Boarini, Chiara; Boffa, Nicola; Boglione, Lucio; Borghi, Vanni; Borgia, Guglielmo; Brancaccio, Giuseppina; Brunetto, Maurizia; Cacciola, Irene; Calabrese, Paolo; Calvaruso, Vincenza; Campagnolo, Davide; Canovari, Benedetta; Caporaso, Nicola; Capra, Franco; Carolo, Giada; Cassola, Giovanni; Castelli, Francesco; Cauda, Roberto; Silberstein, Francesca Ceccherini; Cecere, Roberto; Chessa, Luchino; Chiodera, Alessandro; Chirianni, Antonio; Ciancio, Alessia; Cima, Serena; Coco, Barbara; Colombo, Massimo; Coppola, Nicola; Corti, Giampaolo; Cosco, Lucio; Corradori, Silvia; Cozzolongo, Raffaele; Cristaudo, Antonio; Danieli, Elena; Monforte, Antonella D’Arminio; Monache, Marco delle; Del Poggio, Paolo; de Luca, Andrea; Dentone, Chiara; Di Biagio, Antonio; Di Leo, Alfredo; Di Perri, Giovanni; DI STEFANO, Marco; D’Offizi, Giampiero; Donato, Francesca; Durante, Emanuele; Erne, Elke; Fagiuoli, Stefano; Falasca, Katia; Federico, Alessandro; Felder, Martina; Ferrari, Carlo; Gaeta, Giovanni Battista; Ganga, Roberto; Gatti, Pietro; Giacomet, Vania; Giacometti, Andrea; Gianstefani, Alice; Giordani, Maria; Giorgini, Alessia; Grieco, Antonio; Guerra, Michele; Gulminetti, Roberto; Ieluzzi, Donatella; Imparato, Michele; Iodice, Valentina; La Monica, Silvia; Lazzarin, Adriano; Lenzi, Marco; Levrero, Massimo; Lichtner, Myriam; Lionetti, Raffaella; Guercio, Carmela Lo; Madonna, Salvatore; Magnani, Silvia; Maida, Ivana; Marignani, Massimo; Marrone, Aldo; Marsetti, Fabio; Martini, Silvia; Masarone, Mario; Maserati, Renato; Mastroianni, Claudio Maria; Memoli, Massimo; Menzaghi, Barbara; Merli, Manuela; Miele, Luca; Milella, Michele; Mondelli, Mario; Montalbano, Marzia; Monti, Monica; Morelli, Olivia; Morisco, Filomena; Nardone, Gaetano; Novara, Sergio; Onnelli, Giovanna; Onofrio, Mirella; Paganin, Simona; Pani, Luca; Parisi, Maria Rita; Parruti, Giustino; Pasquazzi, Caterina; Pasulo, Luisa; Perno, Carlo Federico; Persico, Marcello; Piai, Guido; Picciotto, Antonino; Pigozzi, Grazielle Marie; Piovesan, Sara; Piras, Maria Chiara; Pirisi, Massimo; Piscaglia, Anna Maria; Ponti, Laura; Potenza, Domenico; Pravadelli, Cecilia; Quartini, Mariano; Quirino, Tiziana; Raimondo, Giovanni; Rapaccini, Gian Ludovico; Rendina, Maria; Rizzardini, Giuliano; Rizzetto, Mario; Rizzo, Salvatore; Romagnoli, Dante; Romano, Antonietta; Rossi, Cristina; Rumi, Maria Grazia; Russello, Maurizio; Russo, Francesca Paolo; Russo, Maria Luisa; Sansonno, Domenico Ettore; Santantonio, Teresa Antonia; Saracco, Giorgio; Schimizzi, Anna Maria; Serviddio, Gaetano; Simeone, Filomena; Solinas, Attilio; Soria, Alessandro; Tabone, Marco; Taliani, Gloria; Tarantino, Giuseppe; Tarquini, Pierluigi; Tavio, Marcello; Termite, Antonio; Teti, Elisabetta; Toniutto, Pierluigi; Torti, Carlo; Tundi, Paolo; Vecchiet, Giacomo; Verucchi, Gabriella; Gentilucci, Umberto Vespasiani; Vinci, Maria; Vullo, Vincenzo; Zolfino, Teresa; Zuin, Massim

Changes in surgicaL behaviOrs dUring the CoviD-19 pandemic. The SICE CLOUD19 Study

BACKGROUND: The spread of the SARS-CoV2 virus, which causes COVID-19 disease, profoundly impacted the surgical community. Recommendations have been published to manage patients needing surgery during the COVID-19 pandemic. This survey, under the aegis of the Italian Society of Endoscopic Surgery, aims to analyze how Italian surgeons have changed their practice during the pandemic.METHODS: The authors designed an online survey that was circulated for completion to the Italian departments of general surgery registered in the Italian Ministry of Health database in December 2020. Questions were divided into three sections: hospital organization, screening policies, and safety profile of the surgical operation. The investigation periods were divided into the Italian pandemic phases I (March-May 2020), II (June-September 2020), and III (October-December 2020).RESULTS: Of 447 invited departments, 226 answered the survey. Most hospitals were treating both COVID-19-positive and -negative patients. The reduction in effective beds dedicated to surgical activity was significant, affecting 59% of the responding units. 12.4% of the respondents in phase I, 2.6% in phase II, and 7.7% in phase III reported that their surgical unit had been closed. 51.4%, 23.5%, and 47.8% of the respondents had at least one colleague reassigned to non-surgical COVID-19 activities during the three phases. There has been a reduction in elective (>200 procedures: 2.1%, 20.6% and 9.9% in the three phases, respectively) and emergency (<20 procedures: 43.3%, 27.1%, 36.5% in the three phases, respectively) surgical activity. The use of laparoscopy also had a setback in phase I (25.8% performed less than 20% of elective procedures through laparoscopy). 60.6% of the respondents used a smoke evacuation device during laparoscopy in phase I, 61.6% in phase II, and 64.2% in phase III. Almost all responders (82.8% vs. 93.2% vs. 92.7%) in each analyzed period did not modify or reduce the use of high-energy devices.CONCLUSION: This survey offers three faithful snapshots of how the surgical community has reacted to the COVID-19 pandemic during its three phases. The significant reduction in surgical activity indicates that better health policies and more evidence-based guidelines are needed to make up for lost time and surgery not performed during the pandemic