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In head and neck surgery, sealant films represent a useful adjunct to ensure a reinforcement preventing leakages, dehiscence or oozing. The aim of this pilot study is to present the potential applications of a new sealant sheet in head and neck surgery, reporting outcomes, advantages and limitations. The sample included 32 patients, that underwent oncologic or elective surgery between January 2019 and January 2021 at the Cattinara Hospital in Trieste, Italy. Data regarding the patient, the surgical procedure and the postoperative course over hospitalization in terms of surgical complications were retrospectively collected. In this study, nor complication during the regular follow-up period occurred neither difficulties emerged in TP use in any head and neck subsites. In our experience, TP represented a valid aid in suture strengthening, easy to apply and suitable also for oncologic surgery in which the closure of some surgical defects may need a greater sealing effect., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Dorsal hump reduction is a crucial point of rhinoplasty, as it has a great impact on the final shape of nasal pyramid. Depending on morphological features of the hump, its removal is usually obtained by the use of an osteotome or a rasp. In our study, we describe a closed rhinoplasty technique performed in 2 groups of patients: the only difference between the groups is the surgical tools used during the dorsal hump removal phase (rasp vs the 5-mm osteotome).We used 2 questionnaires of quality of life (QoL), Nasal Obstruction Symptom Evaluation (NOSE), and Rhinoplasty Outcome Evaluation (ROE) questionnaire, to evaluate postoperative outcome (6 months after surgery).Closed rhinoplasty was performed in 107 patients. Dorsal hump removal was carried out with rasp on 35 patients; while in 72 cases, it was performed using a 5-mm osteotome. All the patients were given 2 copies of NOSE and ROE questionnaires (1 month before surgery and 6 months after surgery) to evaluate postoperative QoL. In our study emerged that the use of osteotome in dorsal hump reduction is associated with a better aesthetic outcome (evaluated by analyzing patients QoL with ROE questionnaire) without any difference between the 2 groups in terms of functional outcome (expressed by NOSE questionnaire), major and minor complications and surgical procedure duration.

Protein induced by vitamin K absence-II (PIVKA-II) is a potential screening marker for hepatocellular carcinoma (HCC). Limited data are available about its utility in discriminating neoplastic from regenerative nodules at ultrasonography (US) evaluation in cirrhotic patients. Aim of this study was to investigate the diagnostic utility of PIVKA-II in cases showing liver nodules of uncertain diagnosis at US.Ninety cirrhotics with US evidence of liver nodule(s) were enrolled. All patients underwent blood sampling within 1 week of US and were thereafter followed up. HCC was confirmed in 40/90 cases, and in all cases it was in a very early/early stage. All sera were tested for PIVKA-II and alpha-fetoprotein (AFP) at the end of follow-up. PIVKA-II at a cut off of 60 mAU/mL was significantly associated with HCC at both univariate and multivariate analysis (P = .016 and P = .032, respectively). AFP at a cut off of 6.5 ng/mL was not associated with HCC at univariate analysis (P = .246). ROC curves showed that PIVKA-II had 60% sensitivity, 88% specificity, 80% positive predictive value (PPV), and 73% negative predictive value (NPV), whereas AFP had 67% sensitivity, 68% specificity, 63% PPV, and 72% NPV. AUROC curves showed that the combination of both biomarkers increased the diagnostic accuracy for HCC (AUC 0.76; sensitivity 70%, specificity 94%, PPV 91%, and NPV 79%).In conclusion, PIVKA-II is a useful tool for the diagnostic definition of US-detected liver nodules in cirrhotic patients, and it provides high diagnostic accuracy for HCC when combined with AFP.

Context: Sclerostin is a circulating inhibitor of the Wnt-signaling pathway produced by osteocytes, which acts as a negative regulator of bone formation. Effects of zoledronic acid on sclerostin serum levels in postmenopausal osteoporosis are unknown., Objective: The purpose of this study was to evaluate sclerostin serum levels after zoledronic acid administration and correlate variations with bone turnover markers., Design and Setting: We conducted a prospective intervention study in an ambulatory care setting., Participants and Intervention: Forty women (mean age 62.6 ± 4.9 years) with postmenopausal osteoporosis were enrolled in this study and randomized into 2 groups to receive zoledronic acid (5 mg) or placebo., Main Outcomes Measures: At baseline and then at 2, 7, 30, and 360 days after zoledronic acid or placebo administration, serum levels of sclerostin, bone-specific alkaline phosphatase (BSAP), as a bone formation marker, and serum C-telopeptide of type 1 collagen (CTX), as a bone resorption marker, were measured., Results: Sclerostin serum levels increased by day 2, reached a peak at day 7 (3-fold baseline, P < .001), and then decreased at day 30 and returned near to baseline after 360 days in the zoledronic acid group. Both CTX and BSAP were reduced, and a significant negative correlation was observed between the percentage changes of sclerostin and the variation in BSAP and CTX at all time points in the zoledronic acid group (P < .05). No changes were observed in the placebo group., Conclusions: Our data demonstrate that zoledronic acid increases sclerostin serum levels and that sclerostin could play a role in coupling bone resorption to bone formation.

Background: The high degree of diversity of the hepatitis B virus (HBV) quasispecies in chronically infected individuals raises the possibility that HBV genetic variants favouring resistance to nucleoside/nucleotide analogues (NAs) might pre-exist to treatment. The aim of this study was to investigate the genetic variability of the entire HBV reverse transcriptase (RT) domain and of the overlapping S gene in a large series of untreated hepatitis B surface antigen carriers and in lamivudine (3TC)-resistant patients., Methods: Sequencing analysis of the entire HBV RT domain of isolates from 100 untreated (treatment-naive group) and 59 3TC-resistant (3TC-resistant group) consecutive patients with chronic hepatitis B was performed., Results: In the treatment-naive group, primary mutations known to cause resistance to NAs were not detected, but variably combined secondary/compensatory mutations were found in 46 (46%) patients. Moreover, four patients carried mutations that modified the S protein antigenicity. In the 3TC-resistant group, besides the primary 3TC-resistant mutations, various combinations of primary and secondary mutations conferring resistance to other NAs were detected in 41/59 (69.5%) patients. Importantly, the RT mutations induced by 3TC provoked stop codons in the overlapping S gene in two patients and modified the S protein antigenicity in another nine., Conclusions: This study shows that HBV mutants associated with resistance to NAs might already be present as the major infecting population in untreated patients, and that variants emerging under 3TC might also carry mutations favouring resistance to other NAs and/or potentially altering the S protein immunoreactivity.

Unlabelled: STUDY SUBJECT: We longitudinally evaluated the virological behaviour and the hepatitis B virus (HBV) genomic variability in inactive HBV surface antigen (HBsAg) chronic carriers., Patients and Methods: Fourteen HBsAg-positive healthy workers (13 inactive carriers and 1 with active HBV infection) were followed up for 12 months by monthly evaluation of aminotransferase, HBV DNA, and IgM anti HBV core antigen (IgM anti-HBc) values. Moreover, HBV serum isolates from each case were amplified, cloned and sequenced to evaluate the presence of the potentially clinical relevant core-promoter and precore mutations. The same technical procedures were used to examine the S gene of isolates from 3 randomly selected inactive carriers and the patients with active HBV infections., Results: Aminotransferase values were constantly normal in all cases. Viremia levels appear to fluctuate widely over time in each individual case, although the HBV DNA remained below 2 x 10(4) copies/ml in all samples. Only four serum samples from two inactive carriers had IgM anti-HBc values higher than the specific cut-off limit of the assay. Either wild type or core-promoter/precore HBV variants or a mixture of them were detected in the inactive carriers. S gene nucleotide homology among the clones from the three inactive carriers and the subject with active infection was 98.9%, 98.3%, 98.1% and 98.2%, respectively., Conclusions: The degree of suppression of HBV replication in inactive carriers is variable over time, and the entity and quality of HBV variability is comparable between active and inactive carriers.

Background/aims: PreS2-defective hepatitis B virus (HBV) variants may emerge during chronic HBV infection. These variants carry mutation(s) at the ATG-start-codon and/or in-frame deletion into the preS2 genomic region and are commonly detected by sequencing analyses. We evaluated the prevalence of these variants in a large series of chronic HBV infected patients through non-sequencing molecular approaches., Methods: We examined HBV isolates from 110 HBV carriers: 15 were inactive carriers (IC); 50 had chronic hepatitis (CH); 25 were cirrhotics; 19 had hepatocellular carcinoma (HCC). The entire preS2 genomic region was amplified by PCR technique. The amplicons were processed: (A) through electrophoresis on acrylamide gel to reveal deleted genomes; (B) through electrophoresis on agarose gel after digestion by NlaIII enzyme that cuts the wild ATG-start-codon but not the mutated one., Results: We detected preS2 variants in 56/110 cases (51%). In particular, we found preS2-defective mutants in 2/15 IC, 25/50 CH, 13/26 cirrhotics, and 16/19 HCC. The presence of these variants was thus significantly associated with active infection and liver disease (P<0.002). Moreover, among cases with liver disease preS2-mutants were more prevalent in HCC patients (P<0.02)., Conclusions: Our non-sequencing molecular methods are sensitive and specific, and simplify the identification of all preS2 HBV variant forms. Infection by these variants is significantly associated with active infection and HCC.

The tissue tropism and possible correlation with liver disease of the TT virus (TTV) as well as its prevalence and genotype distribution remain undefined. TTV-DNA was investigated in paired sera and tissue samples from 144 patients, and sera and cerebrospinal fluids (CSF) from additional six subjects. Of the 144 tissue samples, 128 were liver biopsy specimens from subjects with hepatic disease while 16 were surgically obtained nonliver specimens from patients with extrahepatic disease. TTV cloning, sequencing and genotype analyses were performed on isolates from sera, tissue specimens and peripheral blood mononuclear cells of two patients with hepatic and four patients with extrahepatic pathologies, as well as from sera and CSFs of two subjects. TTV was found in 100% of the examined tissues and in 60.1 and 50% of sera from patients with hepatic and extrahepatic pathologies, respectively. Moreover, TTV was detected in four of the six CSFs analysed but only in two correspondent sera. Genotyping revealed the coexistence of multiple TTV genotypes and genetic variants in each infected individual, and the analysis of TTV mRNA showed the presence of transcripts in all the six different tissues studied. These results indicate that the entire adult population in our area is more likely infected by TTV, although several subjects are not viraemic and that TTV infects many different human tissues and is able to invade the central nervous system.

Nonstructural protein 5A (NS5A) of the hepatitis C virus (HCV) may repress the interferon (IFN)-induced protein kinase R (PKR). High variability of different regions in the carboxy-terminal half of NS5A implicated in the interaction with PKR (particularly the interferon sensitivity determining region (ISDR)) may be a predictor of response to IFN in patients infected with genotype 1b of HCV. We examined pretreatment serum samples from 17 HCV-1b infected patients included in the same schedule of IFN therapy. Seven patients were a rare series of sustained responders (SR) with a post-treatment follow-up of 5-7 years, while ten were nonresponders (NR). The carboxy-terminal half of the NS5A gene was amplified and directly sequenced in all 17 cases. In addition, the entire NS5A gene and the part of the HCV E2 gene coding for the hypervariable region 1 (HVR1) were amplified, cloned and sequenced in six cases (three NR and three SR). No difference in number and distribution of amino acid mutations was observed between isolates from SR and NR in any portion of the protein, including the ISDR region. Analysis of full length NS5A confirmed no difference between the two groups. The NS5A gene sequence was different among the six cases cloned although it appeared to be conserved in each individual patient independently of the quasispecies complexity evaluated through HVR1 examination. These data indicate that pretreatment analysis of theNS5A genomic variability has no value in predicting long-lasting response to IFN therapy in HCV-1b-infected patients, and that the HCV NS5A gene has high quasispecies homology.

No data are available about the amount of hepatitis B virus (HBV) genomes in liver of patients with chronic HBV infection. The aim of this study was to quantify the intrahepatic HBV DNA in hepatitis B surface antigen (HBsAg)-positive patients with either active or suppressed viral replication and in HBsAg-negative subjects with occult HBV infection. We optimized the Roche "Amplicor HBV Monitor" kit for quantifying liver HBV DNA and analyzed hepatic DNA extracts and serum samples from 19 HBs-Ag-positive and 43 HBsAg-negative individuals. Eight of the HBsAg carriers had active HBV replication, and for 3 of them we analyzed samples obtained before and at the end of 1 year of lamivudine treatment. Five hepatitis Delta virus (HDV) coinfected patients and 6 healthy HBsAg carriers had inhibited HBV activity. Among the HBsAg-negative subjects 21 had occult HBV infection and 22 had no evidence of HBV infection. The median of HBV genomes per microgram of liver DNA milliliter of serum was 34,500 to 2,620,000 in patients with active viral replication, 20,000 to 3,900, 000 before and 10,000 to 2,800 at the end of therapy in lamivudine-treated individuals, 9,800 to 600 in HDV-infected individuals, and 7,450 to 17,400 in healthy HBsAg carriers. These data indicate that cases with suppressed HBV activity, despite the very low levels of viremia, maintain a relatively high amount of intrahepatic viral genomes. This virus reservoir is likely involved in HBV reactivation, which is usually observed after stopping lamivudine treatment. Finally, the analysis of cases with occult HBV infection showed that the assay we used was able to specifically detect and quantify as few as 100 copies of viral genomes per microgram of liver DNA.

Background/aims: Hepatitis B virus (HBV) core gene heterogeneity may influence the outcome of liver disease and the response to interferon (IFN) therapy in adult HBV carriers. The aim of this study was to evaluate the possible association between HBV core gene variability and evolution of chronic hepatitis in children., Methods: We examined serum samples from 25 children with HBV chronic hepatitis and HBe antigen (HBeAg) positivity who were followed-up for a mean of 7.4 years. Seven cases spontaneously seroconverted to anti-HBe, becoming HBV healthy carriers; nine cases were successfully treated with IFN; nine cases were non-responders to IFN therapy. HBV-DNA was extracted from one serum sample ("I") collected during the HBeAg positive phase, and from a second sample ("II") collected after the anti-HBe seroconversion or, in non-responders, after stopping therapy. The entire core gene of the HBV isolates was amplified and sequenced., Results: Each isolate showed single or no missense mutation independently of the clinical behavior of the patients. HBeAg-defective viruses were detected in one case in both samples and in two cases only in sample "II"., Conclusions: Core gene variability does not seem to be involved either in the outcome of infection or in the response to IFN treatment in children with HBV chronic hepatitis. Considering that most of the HBV carriers in our area acquire the infection in childhood, our data suggest that core gene heterogeneity is not a major cause of progression to chronicity.

Development of type 1 insulin-dependent diabetes mellitus has been recently reported in patients who underwent interferon-alpha (IFN-alpha) therapy because of chronic viral hepatitis. Furthermore IFN-alpha seems to be involved in the immunological events that lead to beta-cell destruction and development of type 1 diabetes. To evaluate whether IFN-alpha treatment could elicit an autoimmune response against beta-cell antigens, we determined the occurrence of islet cell antibodies and insulin autoantibodies in the sera of 60 patients with HCV- or HBV-related chronic hepatitis who had been treated with IFN-alpha for 6 or 12 months. The presence of antibodies against thyroglobulin, thyroid microsomal antigen, gastric parietal cells, and non-organ-specific antigens was also investigated. Insulin autoantibody positivity was observed in 2/60 (3.3%), 8/60 (13.3%), and 4/30 (13.3%) patients, before IFN-alpha treatment, and after 6 months and 12 months of therapy, respectively. None of the studied patients developed islet cell antibodies or type 1 diabetes. Before IFN-alpha therapy four patients showed thyroid autoantibodies and four others developed antibodies against thyroglobulin and/or thyroid microsomal antigen during the treatment. Coexistence of insulin autoantibodies and thyroid autoantibodies was observed in only two patients. Our results showed that IFN-alpha therapy in patients with chronic viral hepatitis is capable of inducing development of autoantibodies against insulin. This event seems to be not related to other autoimmune disorders.

Objectives: To evaluate whether peculiar histological changes are present in liver tissue of patients with chronic hepatitis by hepatitis B and hepatitis C (HBV and HCV) virus combined infections., Methods: We studied liver biopsy specimens from 14 HB surface antigen/anti-HCV-positive patients consecutively admitted to hospital because of chronic liver disease from 1987 to 1992. Alcohol abusers, drug addicts, hepatitis delta virus- and HIV-infected subjects were excluded from the study. All of them were positive for serum HBV-DNA and/or intrahepatic HB core antigen and for serum HCV-RNA. Histological examination showed mild or moderate chronic hepatitis in nine cases and severe chronic hepatitis with cirrhosis in five cases. Two additional sets of liver biopsy specimens were also included in the study, consisting of liver samples from 14 patients with chronic liver disease due to active HBV infection alone (group B) and from 14 patients with active HCV infection alone (group C). Cases from group B and C matched for age, sex, and histological diagnosis with those from group B + C. Histological patterns of all the liver specimens of the three groups were re-examined by two authors who scored the found features using a scale from 0 to 3., Results: No peculiar histological pattern was revealed in group B + C, and most of the detected microscopic features were similarly present in all three groups. Bile duct lesions and well defined lymphoid follicles were found only in liver samples of patients from groups C and B + C. Ground-glass hepatocytes were observed only in cases from the groups B and B + C., Conclusions: Histological examination of liver tissue from patients with chronic HBV and HCV combined infection does not show either typical patterns or evidence that this subgroup of chronic viral hepatitis is a more severe form of liver disease than that caused by a single virus infection. The observation in liver samples of peculiar lesions by HBV or HCV infection does not exclude a combined infection by both viruses.

We analysed DNA extracted from liver biopsy specimens and serum samples from 42 HCV-RNA-positive/HBsAg-negative subjects with chronic hepatitis. Twenty-eight of them were anti-HBs/anti-HBc-positive (group A), while 14 were negative for all HBV markers (group B). HBV sequences were found in hepatic DNA of 12 cases (11 of group A, one of group B), but in the serum of only two cases of group A. Sequencing analysis of pre-core region of HBV-DNA showed the presence of wild-type HBV in three cases, HBeAg-defective HBV in three cases, and the coexistence of both viral populations in six cases. These results indicate that HBV and HCV infection may coexist in HBsAg-negative chronic hepatitis, particularly in anti-HBs/anti-HBc-positive patients. However, HBV replication appears suppressed in these cases, and this state of latency may involve both wild and HBeAg-defective HBV types.

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to anti-hepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3-4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G+A), indicating a mixture of wild-type and "e minus" variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity.

We analyzed hepatitis B virus (HBV) genomes obtained from serum samples and liver biopsy specimen of a chronic HBsAg/anti-HBe carrier with hepatocellular carcinoma (HCC). Before the liver biopsy, performed at the time of HCC diagnosis, the patient had been followed for 2 years; the serum samples collected in that period resulted negative for HBV-DNA dot blot hybridization. The hepatic DNA was at first examined by Southern blot, but no HBV sequence was detected. Polymerase chain reaction (PCR) amplification revealed the presence of HBV genomes in DNA extracted from the liver tissue and from two serum samples collected, respectively, 1 and 2 years before the biopsy. Direct sequence of the amplified preC/C and preS regions showed that the viral populations present in serum and liver were identical and that they had a 34 nucleotide deletion in the preS2 region, while the preC region presented two mutations each introducing a translational stop codon, one at the carboxy terminal end and the other at the second codon of the region, both able to prevent HBeAg expression. These results identify a new HBV variant which was selected during a chronic infection, and had very low levels of replication as shown by its detection only after PCR amplification.

The histological features in liver biopsy specimens from seven patients with acute exacerbation of chronic type B hepatitis were analysed. In all the cases typical changes of acute hepatitis were superimposed on signs of chronicity, namely peripheral piecemeal necrosis, plasma cell infiltration and porto-portal bridges, which in three cases contained elastic fibres. Reactivation of silent hepatitis B virus chronic infection should be considered as a possible diagnosis in any patient with histological findings of acute and chronic hepatitis.

The presence of HBV-DNA sequences was evaluated in DNA extracted from serum samples, peripheral blood lymphocytes and liver biopsy specimens of five HBsAg/anti-HBe-positive carriers with chronic HDV infection. DNAs were tested by polymerase chain reaction (PCR) amplification technique using two pairs of oligonucleotide primers specific for the preC/C and S regions of the HBV; viral sequences were found exclusively in liver extracts and only in three out of the five cases. The direct sequencing of the amplified preC/C regions showed wild-type sequences in two cases, while in the third case a combination of 'wild' and 'e minus variant' viral populations was observed. Moreover, liver DNA of one positive case was electrophoresed through a low melting agarose gel and the following amplification, performed on DNA re-extracted from three different fragments of the gel, showed the presence of free HBV genomes but the absence of replicative intermediate forms. These results show that anti-HBe positivity is not constantly related to precore mutant HBV infection and suggest that HDV inhibits HBeAg production. Moreover, as it was observed in 'e minus' HBV variants, also during a chronic HBV wild-type infection, the viral replication might be suppressed to undetectable levels.

We analysed the serum samples and the liver biopsies of six consecutive chronic HBsAg/anti-HBe carriers admitted to hospital because of an episode of acute hepatitis. The six patients became positive for IgM anti-HBc and negative for HBeAg, hepatitis Delta virus (HDV) markers, IgM anti-hepatitis A virus (HAV), anti-cytomegalovirus (CMV) and anti-Epstein-Barr virus (EBV). Two patients showed positivity for hepatitis B virus (HBV)-DNA in serum obtained on admission, with no positivity in the subsequent weeks; the results of the other four patients were always negative for seric HBV-DNA. The Southern-blot analysis of the DNA extracted from the liver tissue of four subjects showed the presence of HBV-DNA in the form of replicative intermediates; focal positivity of HBcAg was detected in the liver of only one. The liver biopsies of the last two patients were negative for HBV-DNA and for HBcAg. The analysis of HBV-DNA in the liver extracts and the demonstration of an increase of the IgM anti-HBc titre at the time of the abrupt elevation of the aminotransferase levels seem to be the most useful tools in revealing HBV activation as a cause of acute hepatitis in chronic HBsAg carriers, overall when the phase of viremia is transient.

The role of active hepatitis B virus (HBV) infection in chronic HBsAg positive hepatitis with and without hepatitis delta virus (HDV) superinfection was analysed in percutaneous liver biopsy specimens from 50 patients. Each specimen was divided into two--one part for histological evaluation and for the detection of HBcAg and delta antigen; the other part was tested for HBV-DNA using Southern blotting. Ten cases were of chronic lobular hepatitis, 10 of chronic persistent hepatitis, and 30 of chronic active hepatitis. Ten cases were delta antigen positive and showed high grade lobular activity but no evidence of HBV-DNA episomal forms or HBcAg reactivity. Twenty one cases showed HBV-DNA replicative intermediate forms; 19 had high grade lobular activity, which occurred in five cases without evidence of free viral DNA. Of the 21 biopsy specimens with HBV-DNA episomal forms, 14 were positive for HBcAg; only one of the 19 cases without detectable viral DNA was positive for such antigen. These data indicate that the presence of HBV or HDV active infection correlates with the histological finding of prominent lobular necrosis. Moreover, intrahepatic HBV-DNA seems to be a more sensitive marker than the presence of viral antigens for indicating HBV replication.