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The onset of chemo- and/or radio-resistance in tumour cells is one of the main causes of failure of integrated treatment protocols combining intra-arterial administration of platinum derivatives and radiotherapy, and is associated with recurrent disease and/or distant metastases. In the present study, the expression of a series of markers of chemo- and/or radio-resistance was investigated in 21 patients with advanced squamous cell carcinoma of the head and neck treated with combined intra-arterial carboplatin and radiotherapy. The results were correlated with local response to treatment, recurrence and overall and disease-free survival. In non-responders or in patients presenting recurrence, caspase 8 was significantly (p 0.05) under-expressed while p-Gp (p 0.035) and MDR-3 (p 0.049) were significantly over-expressed. Tumours with unfavourable outcome more frequently over-expressed two or more anti-apoptotic factors (p-53, BCL-2, BCL-x) (p 0.01). Patients with shorter overall survival, significantly over-expressed p53 (p 0.04), LRP (p 0.038) and a larger number of trans-membrane transport proteins compared with those who survived more than one year (p 0.013). Finally, patients with the shortest disease-free survival presented over-expression of p53 (p 0.027) and BCL-x (p 0.023). Further studies are necessary to confirm the possibility, in a future perspective, of using a panel of markers of chemo- and radio-resistance to identify those patients potentially sensitive to the treatment and to avoid patients at high risk of resistance from being submitted to ineffective and toxic treatment protocols.

To estimate whether pretreatment serum iron levels, the HIC (hepatic iron concentration) and the distribution of hepatic iron identify the long-term "responders" and "non-responders" to therapy with peg-IFN and RBV, and whether the addition of phlebotomy could increase the likelihood of therapeutic response.45 subjects with chronic hepatitis C were taking peg-IFN alpha-2a 180 microg once a week and RBV 1000 mg/die. The "responders" continued therapy with peg-IFN plus RBV, while, the "non-responders" were subjected to phlebotomy. After two weeks and subsequently every month the patients were subjected to blood test and clinical appraisal.Hepatic iron storage meaningfully conditions the outcome of therapy with peg-IFN and RBV, its reduction by phlebotomy favourably correlates with response to treatment and, at last, the semiquantitative histological appraisal would have to be included in the pre-treatment work-up of patients with chronic hepatitis C.The study results, even though obtained on a small size of cases, allow to conclude that serum corporeal iron evaluation underestimates the real hepatic iron concentration; the hepatic iron concentration, in turn, negatively conditions the response to therapy with peg-IFN and RBV (by reducing the percentage of the fast virological response). Lastly, iron removal by phlebotomy favourably correlates with the response to treatment.

The aim of this paper was to assess circulating levels of metalloprotease2 (MMP2), metalloprotease9 (MMP9) and tissue inhibitor of metalloprotease2 (TIMP2) in patients with HCV-related chronic hepatitis to verify whether there was a relationship between these molecules and biochemical and histological features.Forty-nine neodiagnosed and untreated patients affected by chronic C hepatitis and twenty healthy control subjects were investigated. In overall study series, circulating levels of MMP2, MMP9 and TIMP2 were assessed by ELISA commercial kit (RD Systems). Patients with chronic hepatitis undergone to liver biopsy and histological features were examined according to Histological Activity Index (HAI).Mean values of MMP2 (1989+/-207 ng/mL. vs 1112+/-120 ng/mL), MMP9 (62.44+/-11.9 ng/mL vs 39.67+/-4.6 ng/mL) and TIMP2 (48.3+/-8.1 ng/mL vs 15.16+/-4.1 ng/mL) were significantly higher (P0.001) in patients than in controls. Among investigated molecules, only MMP2 was independently related to inflammation and fibrosis according to grading (P=0.036) and staging (P=0.032) score. Moreover, MMP2 but not MMP9 and TIMP2 was related to AST (P=0.015), ALT (P=0.049) and AST/platelet ratio index (P=0.001). No relationship (P0.05) was found between MMP2 and MMP9 or TIMP2.Our study confirms an altered pattern of metalloproteases and their tissue inhibitors in subjects with chronic C hepatitis and such alterations can contribute to development of liver fibrosis. In addition MMP2 is related to inflammation and fibrosis as assessed by liver biopsy and laboratory features. The serial detection of MMP2 could help to monitor evolution of disease and to predict onset of cirrhosis.

Surgical resection is one of the standard therapeutic choices for the treatment of hypopharyngeal cancer, whether or not combined with postoperative radiotherapy. The type of operation depends on the extension of the lesion and the subsites involved and often requires some form of reconstruction. Reconstructive strategies depend on whether the larynx, or part of it, has been preserved. We believe that the decisional flow-chart of the reconstructive methods after hypopharyngeal cancer resection should be based not only on the extent of resection, but also on the subsites involved. This report presents a literature review on the management of cancer of the hypopharynx and a proposal for a surgical decisional flow-chart.L'intervento chirurgico è il trattamento di scelta per il trattamento dei tumori ipofaringei, associato o meno a trattamento radioterapico post-operatorio. Il tipo di chirurgia dipende dall'estensione della lesione e dalle sottosedi interessate. Frequentemente si rende necessaria una ricostruzione e le strategie adottate dipendono dalla possibilità o meno di preservare la laringe. Riteniamo quindi che l'algoritmo decisionale per la ricostruzione o meno dopo chirurgia dell'ipofaringe debba essere basato non solo sull'estensione della resezione ma anche sulla sottosede coinvolta. Questo lavoro presenta una revisione della letteratura sulla gestione del cancro dell'ipofaringe ed una proposta di algoritmo decisionale chirurgico.

In medical practice we frequently encounter autoimmune syndromes, called "overlap-syndromes," which are of difficult nosographic classification because of the presence of sero-immunologic and clinical features common to various diseases having an autoimmune pathogenesis. Some of these syndromes have already been extensively described in scientific literature such as, for example, the presence of clinical and biohumoral alterations with hepatic and extrahepatic involvement, in the course of viral and autoimmune chronic hepatitis. The described clinical case can be classified as a new "overlap syndrome": Type 1 autoimmune hepatitis (AIH)/Primary pulmonary hypertension (PPH). Although the presence of pulmonary hypertension has been extensively described in the course of various connective tissue diseases (S.L.E., Mixed Connective Tissue Disease, Scleroderma, Hashimoto's Thyroiditis, Sjögren's Syndrome), in recent scientific literature, the association is quite rare. The interest in the described clinical case lies both in the possibility to classify it in the context of a more complex "overlap syndrome" AIH/PPH and in the correlated diagnostic and therapeutic implications. Therefore, in cases of primary pulmonary hypertension, a thorough immunological and hepatic functionality study is always recommended in order to ensure an early diagnosis and a prompt AIH treatment, thus warding off the risk of a rapid progression in cirrhosis.

Epidemiological studies report that in Sicily reside about 30,000 citizens with a diagnosis of chronic hepatitis due to HCV. The availability of direct antiviral action (DAA) is a real therapeutic breakthrough, but the high cost of the therapeutic regimes limits their use and forced the National Health System to establish clinical priority for the treatment.The HCV Sicily Network is a web-based model of best medical practice, which was designed to improve the management and the treatment of HCV chronic hepatitis and cirrhosis. The network includes 41 centers and 84 gastroenterologists or infectivologists connected by a web platform that recorder the diagnosis and the clinic priority for the therapy.From March 2015 to September 2016, 9,965 patients (57% male, mean age 61 years, 34% with age over 70 years) have been recorded in the web platform, 3,319 patients completed the treatment, and 1,754 completed the 12 weeks of follow-up. The Sustained Virological Response (SVR) was achieved in 1,541 patients (87.8%), while 136 patients (7.7%) 77 patients (4.5%) experienced a virological relapse during the 12 weeks of follow-up.The HCV Sicily Network is an excellent system for the Regional Department of Health that can have a real estimation of patients that received an efficacy, but high-cost therapy.

Carbohydrate 19-9 antigen (CA 19-9) has been used in the diagnosis and follow-up of gastrointestinal tumors. However, a remarkable reduction of specificity has been described in subjects with chronic diseases. Elevated CA 19-9 serum levels have been described in non neoplastic liver diseases, such as hepatic cirrhosis, where they correlate with the fibrosis grade and the disease severity. The aim of the study is to evaluate CA 19-9 levels in chronic hepatitis patients (CH) and hepatic cirrhosis patients, Hepatitis C Virus (HCV)-correlated. Our goal was to establish whether elevated CA 19-9 levels can be considered a non casual event in chronic liver disease and whether a correlation can be found between CA 19-9 levels and the severity of the disease.116 patients have been recruited (76 m, 40 f, average 54 years); 56 patients were affected by CH and 60 by hepatic cirrhosis (Child A). All patients were HCV+, genotype 1b. Patients positive to CA 19-9 high levels were subjected to abdominal echography, EGDS, colonscopy, abdominal CT.Fifty two percent presented high levels of CA 19-9. None was affected by intestinal or pancreatic neoplasia, or colestatic icterus. CA 19-9 levels were elevated in 46% of patients with chronic hepatitis, and in 54% in patients with hepatic cirrhosis. Furthermore, CA 19-9 levels in hepatic cirrhosis compared to CA 19-9 levels in chronic hepatitis was statistically significant (P0.007).Increased serum levels of CA 19-9 are frequent in chronic viral hepatitis; this often does not indicate a contemporary neoplastic disease and correlates in a statistically significant way (P0.007) with the severity of the disease.

Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis., Graphical abstract, Highlights • Under real-world conditions, OCA was effective in ~43% of patients who were non-responders to UDCA, according to Poise criteria. • Patients with cirrhosis showed lower efficacy (29.5%), mainly attributed to reduced tolerability and higher discontinuation rate. • Patients with overlap AIH-PBC showed a comparable efficacy to pure PBC, with a higher ALT reduction at 6 months. • Most patients with PBC are still in need of additional therapy if aiming to normalise liver biochemistry.

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3±11.6years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta −2.37, p&nbsp

Background: Dysphagia in the elderly, known as presbydysphagia, has become a relevant public health problem in several countries. Swallowing disorders may be a consequence of different neurological disorders (secondary presbydysphagia) or the expression of the aging process itself (primary presbydysphagia). We aimed to test the therapeutic potential of two different non-invasive brain stimulation (NIBS) techniques in subjects with primary or secondary presbydysphagia. Methods: A blinded randomized controlled trial with crossover design was carried out in 42 patients, randomly assigned to anodal transcranial direct current stimulation (tDCS) or intermittent theta-burst stimulation (TBS) group. Both tDCS and TBS were applied for 5 consecutive days over the right swallowing motor cortex. The swallowing function was assessed before and 1 and 3months after the stimulation using the Dysphagia Outcome and Severity Scale (DOSS), scored based on clinical assessment and fiberoptic endoscopic evaluation of swallowing. An electrophysiological method was also applied to evaluate changes in the reproducibility of the swallowing behavior. Key Results: Both real tDCS and TBS had beneficial effects on the swallowing function in patients with primary and secondary presbydysphagia. Anodal tDCS resulted in an improvement of 0.5 points in DOSS at 1-month follow-up (P=.014), whereas intermittent TBS induced an increase of 0.7 and 0.6 points at 1- and 3-month follow-up evaluations, respectively (P=.0001 and P=.005, respectively). Reproducibility of both the oral and pharyngeal phases of swallowing significantly increased at 1-month follow-up. Conclusions and Inferences: Our results suggest that non-invasive cortical stimulation may be useful for dysphagia recovery in elderly patients.

Background & Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI 0.17–0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR 0.70; 95% CI 0.44–1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR 0.32; 95% CI 0.13–0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00–0.19; p

Lembo d’avambraccio radiale vs lembo d’avambraccio ulnare: uno studio preliminare sulla morbilità del sito donatore.L’obiettivo di questo studio era di confrontare la morbilità del sito donatore dopo chirurgia ricostruttiva con il lembo libero d’avambraccio ulnare (UFFF) e il lembo libero d’avambraccio radiale (RFFF) con metodiche soggettive. Il UFFF e il RFFF sono stati utilizzati per la ricostruzione del difetti dei tessuti molli della testa e del collo in 30 pazienti (20 M e 10 F; range d’età 28-75 anni), affetti da carcinoma squamocellulare della testa e del collo. Il questionario sulla disabilità per l’arto superiore DASH è stato usato per valutare la morbilità del sito donatore. L’analisi del punteggio DASH dei pazienti ha dimostrato una mediana del punteggio totale DASH di 9,17. Non sono state osservate differenze significative per i valori mediani dei gruppi RFFF e UFFF (7,14 vs 10, rispettivamente) e per i valori ottenuti dai maschi e dalle femmine (5 vs 13,3, rispettivamente). Il UFFF può essere considerato una valida alternativa al RFFF per la ricostruzione dei difetti dei tessuti molli del distretto testa-collo; è affidabile, semplice da trapiantare e non causa maggiori morbilità del sito donatore come dimostrato dal questionario DASH.The objective of this study was to compare donor site morbidity after reconstructive surgery with Ulnar Forearm Free Flap (UFFF) and Radial Forearm Free Flap (RFFF) with subjective methods. The UFFF and the RFFF were applied for reconstruction of soft tissue defects of the head and neck region in 30 patients (20 M and 10 F; age range 28-75 years) affected by head and neck squamous cell carcinoma. The Disability of Arm, Shoulder and Hand (DASH) questionnaire was used to assess morbidity of the donor site. Analysis of the patients’ DASH scores showed an overall median DASH total score of 9.17. No significant differences were observed for median values of the RFFF and UFFF groups (7.14 vs 10 respectively) or for the values in males and females (5 vs 13.3 respectively). The UFFF can be considered a valid alternative to the RFFF for reconstruction of soft tissue defects of the head and neck area; it is safe, easy to harvest and is not associated with major morbidities of the donor site as demonstrated by the DASH questionnaire.

Background & aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV) after successful treatment of early hepatocellular carcinoma (HCC) has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We enrolled prospectively 163 consecutive patients with HCV-related cirrhosis and at first diagnosis of early Barcelona Clinic Liver Cancer (BCLC) 0/A HCC who had achieved a complete radiologic response after curative resection or ablation, subsequently treated with DAAs. DAA-untreated patients from ITA.LI.CA. cohort (n = 328) served as controls. After propensity-score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. Results: In DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in DAA group compared with No DAA group (hazard ratio [HR] = 0.39; 95% confidence Interval [CI] = 0.17–0.91, p = 0.03). HCC recurrence was not significantly different between DAA and No DAA groups (HR = 0.70; 95%CI = 0.44–1.13, p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in DAA group compared with No DAA group (HR = 0.32; 95%CI = 0.13-0.84, p = 0.02). In DAA group, sustained virologic response was a significant predictor of overall survival (HR 0.02, 95%CI 0.00–0.19, p < 0.001), HCC recurrence (HR 0.25, 95%CI 0.11–0.57, p < 0.001) and hepatic decompensation (HR 0.12, 95%CI 0.02-0.38, p = 0.02). Conclusions: In patients with HCV-related cirrhosis and previous successful treatment of early HCC, DAAs significantly improved OS compared with No DAA treatment.

Background and aim: Response to ursodeoxycholic acid (UDCA) is crucial for the prediction of primary biliary cholangitis (PBC) prognosis, and different response criteria were validated and proposed by reference centers for PBC. To date, rates of non-response to UDCA from real-world series are lacking.Methods: Hepatology/Gastroenterology centers belonging to 'Club Epatologi Ospedalieri' (CLEO) and 'Associazione Italiana Gastroenterologi Ospedalieri' (AIGO) were invited to participate in the study, and asked to extract all patients followed for PBC, without any selection or exclusion, and fill in the database provided.Results: Thirty-four centers were enrolled throughout Italy, for a total of 713 patients. None of these centers, except one, had a hepatology outpatient clinic devoted to the care of patients with autoimmune liver diseases. After excluding 79 cases of PBC/autoimmune hepatitis overlaps, 634 patients were analyzed: mean age, 64.4 ± 12.0 years; 91.2% females; F/M 10.3/1. For patients with at least 1 year of UDCA treatment (583), rates of non-response to UDCA were evaluated according to the Paris-I/-II, Toronto and GLOBE criteria, and compared with those in the original cohorts: 27% vs 39% in Paris-I cohort; 39.6% vs 52% in Paris-II; 20.1% vs 43.5% in Toronto; 15.7% vs 30% in GLOBE (age-specific cutoffs). Mean alkaline phosphatase levels on UDCA treatment, and the age-adjusted prevalence of F3/F4 fibrosis, appeared lower in this PBC population than in reference cohorts.Conclusions: A mean ∼15% better response to UDCA is observed in a real-world PBC population, probably due to migration of some of most severe/advanced cases to PBC referral centers.

Background and aims: Large scale, real life data on the long term course of liver disease after HCV clearance obtained with DAAs are still scanty, and the separate effects on hepatic and non-hepatic causes of death still unclear. Method: We evaluated 4147 patients (mean age: 65.7 ± 11.5 years, 57.6% males) included in the prospective RESIST-HCV cohort who started DAAs treatment in 22 centres between March 2015 and April 2017. All patients were follow after SVR to register liver-related and unrelated outcomes. The primary endpoint was the evaluation of survival since starting DAAs. Cox regression analysis was used to assess the predictors of liver-related and unrelated death. Results: Patients were observed for a median of 50 weeks (range: 1–199), 934 (22.5%) had diagnosis of chronic hepatitis (F3 in >90%), 2851 (68.7%) had Child A cirrhosis and 362 (8.7%) had Child B cirrhosis. Overall, 3766 patients (90.8%) achieved SVR while 381 patients (9.2%) were HCV-RNA positive at the last control. Fifty-five patients (1.3%) died during the observation: 25 of them died for liver related causes and 30 for unrelated causes (16: cardiovascular disease, 6: sepsis, 8: other). The lack of SVR was associated with an increased incidence of overall mortality in comparison to patients with SVR (hazard ratio [HR]; 28.9; 95% confidence interval [CI]: 16.5–50.8; p < 0.001) and death from liver-related and unrelated causes (HR: 18.5, 95%CI: 8.2–41.3; p < 0.001 and HR: 45.5; 95%CI: 19.3–107.4; p < 0.001 respectively). By multivariate Cox regression analysis lack of SVR (HR: 14.9, 95%CI: 6.3–35.1; p < 0.001) and Child B cirrhosis (HR: 29.4, 95%CI: 3.8–223.9; p < 0.001) were independently related with liver mortality. Independent predictors of liver-unrelated mortality were no SVR (HR: 41.77, 95%CI: 17.30–100.87; p < 0.001), Child B cirrhosis (HR: 3.00, 95%CI: 1.36–6.22; p = 0.006), BMI (HR: 0.89, 95%CI: 0.81–0.98, p = 0.023) and diabetes (HR: 2.38, 95%CI: 1.13–5.00, p = 0.022). Conclusion: In this real world setting using a variety of DAA regimens SVR reduced overall mortality and risk of liver-related and unrelated deaths at all stages of disease, nut mostly in Child A cirrhosis. The effect on cardiovascular deaths, which is evident also in the pre-cirrhotic stages deserves further follow up and investigation.

Background & Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. Results: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P

The supraclavicular artery island flap (SCAIF) is a thin and pliable pedicled flap that is easy and quick to harvest. Thanks to its particular features and high reliability, it is best indicated for the elderly or most fragile patients. SCAIF is very versatile, as it can be used for reconstruction of oral cavity, oropharynx, hypopharynx, facial and cervical skin and tracheostomal defects. We began using this flap in four Italian tertiary referral centres, with several indications, both as first treatment and as salvage surgery. The aim of the study was to demonstrate the easy reproducibility of the flap among four different centres. A series of 28 patients underwent head and neck reconstructions with SCAIF with no recorded complications during flap harvesting. After the very first cases, harvesting time was approximately 45 minutes; 24 patients had successful flap integration at the recipient site, while the remaining 4 suffered from partial flap necrosis, two of whom needed revision surgery. Other minor complications were reported at the recipient site, always at the most distal and most delicate portion of the flap. Donor site was always closed primarily, with only three cases of partial suture dehiscence. We only selected the most fragile patients for SCAIF reconstruction, such as the elderly or those with one or more comorbidities; for this reason, we reported some serious systemic complications and one intraoperative death. SCAIF is an easy reproducible flap, with multiple possible indications. Its use as an alternative to free flaps in the head and neck region is nowadays under discussion. Its use should be encouraged among head and neck surgeons thanks to its various advantages.Il lembo peduncolato sovraclaveare (SCAIF) nella ricostruzione del distretto testa-collo: esperienza multicentrica italiana.Il lembo peduncolato sovraclaveare è un lembo sottile e malleabile, facile e veloce da scolpire. Grazie alle sue peculiari caratteristiche e alla sua alta affidabilità trova un’ottima possibilità di utilizzo nei pazienti più anziani o più compromessi. Si tratta di un lembo molto versatile, che può essere utilizzato per ricostruzioni del cavo orale, dell’orofaringe, dell’ipofaringe, della cute della regione della faccia e del collo e dei difetti del tracheostoma. Abbiamo iniziato ad utilizzare il lembo sovraclaveare in quattro centri italiani di riferimento, con diverse indicazioni, sia come prima scelta ricostruttiva, sia come terapia di salvataggio. Con il presente studio ci si propone di dimostrare la agevole riproducibilità del lembo nei quattro diversi centri. 28 pazienti sono stati trattati con ricostruzione del distretto testa-collo mediante lembo peduncolato sovraclaveare, senza evidenza di complicanze durante l’allestimento del lembo. Dopo i primissimi casi, il tempo di allestimento si è stabilizzato attorno ai 45 minuti. In 24 casi si è verificata un’ottima integrazione del lembo nel sito ricevente, mentre i restanti 4 pazienti hanno sofferto una parziale necrosi del lembo, e 2 di essi hanno necessitato di una revisione chirurgica. Altre complicanze minori sono state riscontrate a carico del sito ricevente, sempre a livello della porzione distale e più delicata del lembo. Il sito donatore è sempre stato chiuso mediante sutura diretta, con solo tre casi di parziale deiscenza della ferita. Sono stati selezionati per ricostruzione mediante lembo peduncolato sovraclaveare solo i pazienti più delicati, ovvero i più anziani o coloro che soffrivano di una o più comorbidità; per questo motivo abbiamo riportato alcune complicanze sistemiche severe e persino un caso di morte intraoperatoria. Il lembo peduncolato sovraclaveare è un lembo riproducibile, con multiple possibili indicazioni. Nonostante il suo utilizzo in alternativa ai lembi liberi nelle ricostruzioni del distretto testa-collo rimanga dibattuto, il lembo peduncolato sovraclaveare dispone di numerosi vantaggi e pertanto il suo impiego andrebbe incoraggiato tra i chirurghi che si occupano di chirurgia ricostruttiva.

Objective To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. Methods We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. Results The reproducibility of oropharyngeal swallowing was significantly reduced both in patients with and in those without clinical signs of dysphagia, with more marked alterations being detected in the dysphagic group. The SI of both phases of swallowing, oral and pharyngeal, correlated significantly with dysphagia severity and disease severity. Conclusions In ALS different pathophysiological mechanisms can alter the stereotyped motor behaviors underlying normal swallowing, thus reducing the reproducibility of the swallowing act. A decrease in swallowing reproducibility could be a preclinical sign of dysphagia and, beyond a certain threshold, a pathological hallmark of oropharyngeal dysphagia. Significance Electrophysiological assessment is a simple and useful tool for the early detection of swallowing abnormalities, and for the management of overt dysphagia in ALS.

Background Triple therapy including Telaprevir or Boceprevir still represents in many European countries the standard of care for patients with Hepatitis C Virus genotype 1 infection. The number of patients who received this treatment resulted generally lower than expected. We investigated, among naive patients, number and characteristics of treatment candidates who were started on triple or dual therapy in comparison to those who were deferred. Patients and Methods 621 naive treatment candidates were prospectively evaluated at each center. Factors associated with decision to defer or treat with dual or triple therapy were investigated by univariate and multivariate analyses. Rates of Sustained Virological Response and safety profile were analysed. Results Of candidates to treatment, 33% did not received it. It was mostly due to high risk of Interferon-induced decompensation. Of 397 patients who were started on treatment, 266 (67%) received triple, 131 dual. Among patient receiving treatment, unfavorable IL28B, severe liver damage and higher albumin were independently associated with the physician decision to administer triple therapy. Sustained Virological Response after dual therapy was 66.4%, after triple 73.7% (p = 0.14). 142 patients received Telaprevir. The choice of Telaprevir-based therapy was associated with higher Body Mass Index and advanced liver disease. Sustained Virological Response rates were 71.1% after Telaprevir and 76.6% after Boceprevir. Conclusions Individualizing treatment with available regimens allows to maximize Sustained Virological Response and to reduce the number of patients who remain untreated. High proportion of patients with severe liver damage urgently need Interferon free treatment.