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Background: The combination of atezolizumab-bevacizumab has been proven to be superior to sorafenib for the treatment of unresectable hepatocellular carcinoma not amenable to locoregional treatments, be-coming the standard of care of systemic therapy.Aim: This study aimed at assessing real-world feasibility of atezolizumab-bevacizumab in patients treated with tyrosine-kinase inhibitors.Methods: Among 1447 patients treated with tyrosine-kinase inhibitors from January 2010 to December 2020, we assessed the percentage of those potentially eligible to atezolizumab-bevacizumab (according to IMbrave-150 trial criteria), and the overall survival of eligible and non-eligible patients.Results: 422 (29%) patients were qualified for atezolizumab-bevacizumab therapy. The main exclusion causes were Child-Pugh class and Performance Status. Adopting the more permissive inclusion criteria of SHARP trial, 535 patients became eligible. The median overall survival of tyrosine-kinase inhibitors patients was 14.9 months, longer in eligible patients than in their counterpart due to better baseline liver function and oncological features.Conclusion: Real-world data indicate that less than one-third of hepatocellular carcinoma patients treated with tyrosine-kinase inhibitors are potentially eligible to atezolizumab-bevacizumab according to the reg-istration trial criteria. These patients have a longer survival than the non-eligible ones. If the selection criteria of atezolizumab-bevacizumab trial are maintained in clinical practice, tyrosine-kinase inhibitors will remain the most used systemic therapy for hepatocellular carcinoma patients.(c) 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background Hepatitis C virus recurrence after liver transplantation is universal, leading to chronic hepatitis and cirrhosis. Aims and patients We evaluated the efficacy and safety of pegylated interferon and ribavirin in 20 patients with recurrent Hepatitis C virus after liver transplantation (10 naive and 10 non-responders to a previous interferon course). Methods Treatment consisted of pegylated interferon alfa-2b (1.0 μg/kg once weekly) and ribavirin (600 mg/daily) for at least 6 months. Therapy continued for an additional 6 months only in patients with undetectable serum Hepatitis C virus-RNA or >2 log drop from baseline levels. Results Eleven out of 20 patients (55%) completed 1 year of treatment. Nine patients (45%) had undetectable Hepatitis C virus-RNA at the end of treatment, six of them were naives and three non-responders. In all of them, virological response persisted 6 months after discontinuation of therapy, so the sustained virological response rate was 60% in naive patients and 30% in non-responders. Conclusions Our results suggest that pegylated interferon plus ribavirin combination therapy may be effective in patients with post-liver transplantation recurrent chronic Hepatitis C, even in those previously non-responders to interferon plus ribavirin. These results need to be confirmed by large studies.

In the field of cardiovascular diseases, elevated levels of serum uric acid (UA) reflect a marked activation of the xanthine oxidase pathway with increase in free radicals production; it is often associated with an inflammatory state, oxygen consumption and endothelial dysfunction. All these associations have been also confirmed in heart failure (HF) but the pathophysiological role of UA in this setting is not well understood. The aim of this study was to evaluate the prognostic role of UA in outpatients enrolled in the Italian Registry of Congestive Heart Failure (IN-CHF).All patients met the European Society of Cardiology (ESC) criteria for diagnosis of HF. We considered patients with complete clinical data and UA level available at the baseline and at 1-year follow-up. The study population was composed of 877 patients aged 63 ± 12 years. One-year mortality was 10.8% and dead patients had a higher level of UA than survivors (7.1 mg dl⁻¹ vs 6.6 mg dl⁻¹, p0.0207). In multivariable full model of analysis, UA did not result in an independent predictor of death in overall population, but only in patients with low body mass index (BMI) (≤22 kg m⁻²) (hazard ratio (HR): 2.38, 95% confidence interval (CI) 1.36-4.18). In this subgroup, a statistically significant gradual relationship between UA and survival was detected starting from values higher than 8 mg dl⁻¹.Elevated level of UA is not an independent predictor of mortality in chronic HF, but it markedly worsens outcome if associated with low level of BMI. This association is likely an indicator of chronic inflammatory and catabolic state.

Background Mitral annular calcification (MAC) is a common echocardiographic finding. Caseous calcification of the mitral annulus (CCMA) is, on the other hand, a less known, rarely described variant, seen as a round mass with a central echolucent area composed of a puttylike admixture of fatty acids, cholesterol, and calcium. The aims of this study were to assess the prevalence of CCMA, assess its morphologic changes over the course of time, and evaluate the patients' characteristics and clinical outcome on follow-up. Methods Between January 2002 and December 2004, 20,468 consecutive patients, referred for transthoracic echocardiography, were included in the study. All patients underwent echocardiographic examinations. Four echocardiographic laboratories participated in the registry. CCMA was defined as a large, round, echodense mass with smooth borders located in annular region, without acoustic shadowing and with central areas of echolucencies resembling liquefaction. Results A total of 2169 (10.6%) patients were given the diagnosis of MAC by 2-dimensional echocardiography. A total of 14 patients (0.64% of all MACs, 0.068% of all studies) were given the diagnosis of echocardiographic findings compatible with CCMA. Six (43%) patients underwent transesophageal echocardiography (TEE) to better evaluate the nature of the mass. A complete TEE examination was performed using 2-dimensional and color flow Doppler, and the best visualizations of the mass were performed by midesophageal 4-chamber view, midesophageal 2-chamber view, and midesophageal long-axis view. More detailed imaging of the masses, above all a better visualization of the central areas of echolucency, the assessment of the posterior mitral leaflet motion, and the assessment of the correct location of the mass was achieved by TEE views. All calcifications were confined to the mitral annulus. The most common symptom was palpitation, which occurred in 43% of the patients. During a mean follow-up of 3.4 ± 1.2 years, one patient died. The cause was unrelated to the annular mass; it was the result of neoplasm. During the follow-up period, in 6 (43%) cases, the studies changed, in regard to the features of CCMA, in comparison with baseline studies, thus likely suggesting a changeable condition. Conclusions This study confirms prior observations that CCMA is a rare and benign condition. It illustrates the potential role of TEE in confirming the precise location of the lesion and in more clearly defining the extent of the involvement of the posterior mitral leaflet. There were no typical clinical characteristics in patients with CCMA although the absolute number of patients with CCMA was too small to be statistically significant. However, CCMA does tend to occur in older patients and all 14 patients with CCMA in this study had hypertension. CCMA may be a dynamic process based on the observation that 3 patients with MAC progressed to CCMA and 3 patients with CCMA reverted back to MAC during the study period. To avoid diagnostic mistakes such as tumor, abscess, or thrombus among echocardiographers, it is important for us to consider a more widespread knowledge of this rare lesion.

Background In the large-scale trial, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-3 (GISSI-3), patients receiving the combination of lisinopril and glyceryl trinitrate benefited most from experimental therapy. Therefore, a multicenter, randomized, double-blind study, Delapril Remodeling After Acute Myocardial Infarction (DRAMI), was designed to assess (1) the possible additive beneficial effect on left ventricular remodeling of nitrates when combined with an angiotensin-converting enzyme inhibitor (ACEI), and (2) the tolerability of a new ACEI, delapril, in respect to lisinopril in patients with large myocardial infarction (MI). Methods A total of 177 patients were randomized to receive delapril plus isosorbide-5-mononitrate (IS5MN) placebo, delapril plus IS5MN, lisinopril plus IS5MN placebo, or lisinopril plus IS5MN starting within the first 36 hours after the onset of symptoms and continuing for 3 months. Results More than 80% of the patients showed extensive ST-segment changes and 36.7% had signs or symptoms of heart failure during the first 36 hours. Over 3 months, IS5MN reduced, by 76%, the increase in LVEDV (17.4 ± 5.0 mL placebo vs 4.2 ± 4.4 mL IS5MN, P = .0439), reversed the increase in LVESV (7.5 ± 3.9 mL placebo vs −5.5 ± 2.9 mL IS5MN, P = .0052), and increased the recovery of LVEF (1.9% ± 1.3% placebo vs 6.7% ± 1.2% IS5MN, P = .0119). Overall, 3-month mortality was 10.2%; the most frequent clinical events were new episodes of severe heart failure (18.1%), persistent hypotension (10.7%), and post-MI angina (18.1%), with no differences between treatment groups. Conclusions Administration for 3 months of IS5MN combined with an ACEI, both started within 36 hours from the onset of symptoms, was safe and effective in reducing LV dilation and dysfunction after MI. The 2 ACEIs, delapril and lisinopril, appeared to be equally well tolerated.

The relationship between consumption of fat in seasoning and risk of breast cancer was considered in a case-control study conducted in Northern Italy of 2663 cases of breast cancer and 2344 controls admitted in the same network of hospitals with acute, non-neoplastic and non-gynaecological conditions. Subjective scores corresponding to three levels (low, intermediate and high) of intake of butter, margarine and oil, together with a combined variable of these three items (“total fat”), were used to evaluate the personal use of fat in seasoning. Compared to low use, a slight but significant increase in risk was observed for intermediate and high intake of butter, oil and total fat with relative risks of 1.5 (95% confidence interval [CI], 1.1–1.9) for high intake of butter, 1.3 (95% CI, 1.0–1.6) for high intake of oil and 1.4 (95% CI, 1.2–1.7) for high intake of total seasoning fat. These results were not materially modified after allowance for a number of identified potentially distorting factors. The results of this study suggest that there is a positive association, although moderate, between breast cancer risk and intake of fat added in seasoning, which may represent an indirect indicator of the subject's attitude towards fat.

This study sought to prospectively assess which factors were related to short-term worsening heart failure (HF) leading to or not to hospital admission, in long-term outpatients followed by cardiologists. The subsequent decision-making process was also analyzed. The study population consisted of 2,701 outpatients enrolled in the registry of the Italian Network on Congestive Heart Failure (IN-CHF) and followed by 133 cardiology centers (19% of all existing Italian cardiology centers). Clinical and follow-up data were collected by local trained clinicians; 215 patients (8%) had short-term decompensation (on average 2 months after the index outpatient visit). Multivariate analysis showed that previous hospitalization, long duration of symptoms, ischemic etiology, atrial fibrillation, higher functional class (New York Heart Association classification III to IV), higher heart rate, and low systolic blood pressure were independently associated with HF destabilization. Poor compliance (21%) and infection (12%) were the most frequent precipitating factors, but a precipitating factor was not identified in 40% of the patients. Poor compliance was more common in women, but no other clinical characteristics emerged as being related with a specific precipitating factor. Fifty-seven percent of the patients with a short-term recurrence of worsening HF required hospital admission; infusion treatment with inotropes and/or vasodilators was necessary in 19% of them. Long-term therapy was changed in 48% of the patients. Thus, in ambulatory HF patients, short-term worsening HF can be predicted according to the clinical characteristics on an outpatient basis. Nearly 1/3 of precipitating factors can be prevented. Patient education and avoidance of inappropriate treatment may reduce the number of relapses.

Background and aims: Interferon-α treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. Methods: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. Results: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls ( P =0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively ( P =0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls ( P =0.0019). Conclusion: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

In the present study, high levels of CD30s, a glycoprotein preferentially expressed and released by T lymphocytes producing Th(2)-type cytokines, were seen in the sera of patients with chronic hepatitis C, and a correlation with histological activity of the disease was found. CD30s levels were assayed in the sera of 29 HCV RNA-positive patients with histologically proven chronic active hepatitis and in 30 healthy blood donors. Thirteen of 29 (45%) HCV patients had CD30s serum levels above the normal range (>20 U/ml). Mean CD30s serum levels were significantly higher in HCV patients than in controls (P

Objective Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. Methods 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. Results Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. Conclusions The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.

Background: interferon-α is able to induce a sustained inhibition of hepatitis B virus replication in about 30–40% of patients with chronic hepatitis B. There is evidence that non-steroidal antiinflammatory drugs can enhance the synthesis of antiviral proteins induced by interferon-α, Aim: to evaluate the efficacy and tolerability of combined therapy with interferon-α plus indomethacin in HBeAg and HBV-DNA positive patients affected by chronic active hepatitis non-responders to a previous interferon-α treatment. Methods: after six months of retreatment with interferon-α (6 MU thrice weekly) six patients were enrolled, without stopping the therapy, to receive interferon-α (with the same schedule) plus indomethacin (25 mg orally twice daily) for an additional six month course. Results: at the end of treatment and after six months of follow-up alanine transaminase normalization was seen in three (50%) and four (66.7%) patients, HBV-DNA loss in one (17%) and three (50%), HBeAg HBeAb serum conversion in one (17%) and two (33%), respectively. The combined therapy was well tolerated and no indomethacin side-effects were observed. The treatment was stopped in one patient after 4 months because of a remarkable increase of alanine transaminase levels, and in another after five months because of hyperthyroidism occurrence. Conclusions: the results of this study, even if obtained in a small number of patients, are encouraging and suggest a randomized controlled trial to be confirmed.

Interferon-α (IFN-α) stimulates the synthesis of antiviral proteins, such as 2′,5′-oligoadenylate synthetase (2′5′-OAS), and activation of arachidonic acid (AA) metabolism seems to constitute the post-receptorial signal induced by this cytokine. We evaluated the in vitro effect of IFN-α, indomethacin (an inhibitor of cyclooxygenase pathway of AA) and IFN-α plus indomethacin on 2′5′-OAS release by cultured liver biopsies of patients with active or inactive HCV infection and uninfected patients with various liver diseases. The results demonstrated that basal 2′5′-OAS release was significantly higher in patients with active HCV infection with respect to uninfected ones. In two HCV-Ab positive but HCV-RNA negative patients, basal 2′5′-OAS was similar to uninfected patients. In HCV-RNA positive patients, indomethacin alone was able to significantly increase the 2′5′-OAS production in a similar fashion to IFN-α alone, while a synergistic effect on 2′5′-OAS increase was seen when biopsies were cultured with IFN-α plus indomethacin. A similar trend was observed in the uninfected and in the HCV-Ab positive but HCV-RNA negative patients, even if the increase did not reach statistical significance. These results confirm the interaction between IFN-α and AA metabolites and suggest an evaluation of the in vivo response of IFN-α plus nonsteroid antiinflammatory drugs combined therapy.

148 LIVER TRANSPLANTATION IN CIRRHOTIC PATIENTS WITH MELD SCORE