Genetic determinants in a critical domain of ns5a correlate with hepatocellular carcinoma in cirrhotic patients infected with hcv genotype 1b

HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain‐1 interacts with cellular proteins inducing pro‐oncogenic pathways. Thus, we explore genetic variations in NS5A domain‐1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype‐1b infected DAA‐naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p < 0.001), M133I (20.6% vs. 3.9%, p < 0.001), and Q181E (11.8% vs. 0.6%, p < 0.001). By multivariable analysis, the presence of >1 of them independently correlates with HCC (OR (95%CI): 21.8 (5.7–82.3); p < 0.001). Focusing on HCC‐group, the presence of these mutations correlates with higher viremia (median (IQR): 5.7 (5.4–6.2) log IU/mL vs. 5.3 (4.4–5.6) log IU/mL, p = 0.02) and lower ALT (35 (30–71) vs. 83 (48–108) U/L, p = 0.004), suggesting a role in enhancing viral fitness without affecting necroinflammation. Notably, these mutations reside in NS5A regions known to interact with cellular proteins crucial for cell‐cycle regulation (p53, p85‐PIK3, and β‐ catenin), and introduce additional phosphorylation sites, a phenomenon known to ameliorate NS5A interaction with cellular proteins. Overall, these results provide a focus for further investigations on molecular bases of HCV‐mediated oncogenesis. The role of these NS5A domain‐1 mutations in triggering pro‐oncogenic stimuli that can persist also despite achievement of sustained virological response deserves further investigation

Chewing and cognitive performance: what we know

In recent years, chewing has been discussed as producing effects of maintaining and sustaining cognitive performance. It is reported that mastication improves cognitive function by activating cerebral cortical activity, and it is important to demonstrate the cognitive effects of masticatory training using various interventions. Recent studies emphasized that chewing gum can attenuate reductions in alertness, suggesting that chewing gum enhances worker performance. Several mechanisms have been proposed to account for the facilitation in performance observed when the gum is chewed during cognitive testing. Chewing gum during exposure to stress decreases plasma and salivary cortisol levels and reduces mental stress, although other studies report no such effect. In addition, chewing reduces stress-induced changes in central nervous system morphology, especially in the hippocampus and hypothalamus. However, further research on the alerting effects of chewing gum and possible improved test performance in these situations is needed

Safety of commercial airflight in patients with craniofacial diseases

The potential risk of pressure changes during commercial air travel causing the expansion of trapped intracranial air in post-operative patients is known. Current studies reveal that it is safe for patients with space-occupying brain lesions to fly various distances. Nevertheless, in patients with pre-flight symptoms thought to be due to mass effect or cerebral oedema, the administration of dexamethasone and anticonvulsants may help minimize the risk of further brain swelling and possible seizures during air flight. Besides other oral manifestations of barometric pressure changes, such as barodontalgia, clinicians should be familiar with this entity, take preventive measures, and periodically examine patients who fly planes. Clinicians should also search for occult pathologies such as leaking restorations or secondary caries lesions. Nevertheless, pneumocephalus is not a contraindication to early post-operative flying. More significant, prospective, multi-institutional studies will be necessary to validate these recent results

Oral health and brain connection: Is there any relationship?

Several studies reported the association between periodontal diseases, a persistent inflammatory process and other chronic ailments such as cardiovascular diseases, diabetes mellitus, Alzheimer’s disease and cancer. Although many epidemiologic data support these associations, a cause-and-effect relationship has not been established. Numerous articles reporting oral bacteria in samples collected directly from brain abscesses confirmed the association between brain abscess and odontogenic infection. Dental diseases can be treated with ambulatory care rather than hospitalization and emergency care. Older adults should establish daily oral hygiene care routines during the early stages of Alzheimer’s disease

Electric toothbrush vs. sonic toothbrush, the effectiveness on gingival inflammation: a randomized clinical trial

AIM: The aim of the study is to evaluate the efficacy of electric or sonic toothbrushes on periodontal inflammation. MATERIALS AND METHODS: A randomized, controlled, one-blind study was conducted. Patients in the test group used sonic toothbrushes (Sonicare FlexCare with ProResults brush head, HX6011, Philips Oral Healthcare Inc, Bothell, Wash), whereas those in the control group used electric toothbrushes (Oral B Professional Care Triumph 4000, Procter & Gamble, Cincinnati, Ohio). Periodontal status was recorded at baseline and 3 months. In total, 60 patients were recruited for the study at baseline. Plaque Index (PI) and Loe and Silness Gingival Index (GI) were used. Student’s t-test repeated was used to compare the mean PI and GI scores obtained between the test and control groups at each time point. RESULTS: In total, 56 subjects completed the study. Significant differences were recorded between the two groups for periodontal parameters at 3 months. In addition, the indices of group Sonic were significantly reduced at 3 months compared to the Roto-oscillatory Group (P <.005). CONCLUSION: Sonic toothbrush reduced parameters of periodontal inflammation more effectively than the electric toothbrush

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

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

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)