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Background: Acute kidney injury (AKI) is a well-known complication of ST-elevation acute myocardial infarction (STEMI) with an adverse impact on prognosis. Since AKI develops more frequently in elderly patients, we hypothesized that its higher incidence in older STEMI patients might explain their increased in-hospital mortality. We assessed the relationship between AKI and in-hospital mortality in patients with STEMI of different age groups., Methods: We retrospectively evaluated 5136 STEMI patients treated with primary percutaneous coronary intervention (pPCI). We defined AKI as ≥0.5 mg/dl creatinine increase in the first 72 h. Patients were grouped according to age (<75 [n = 4040] or ≥ 75 [n = 1096] years). The primary endpoint was in-hospital mortality., Results: The incidence of AKI was 7%. It was 4.6% in patients <75 years and 15.1% in those ≥75 years (P < 0.0001). The overall in-hospital mortality was 4%. It was 2.6% and 8.5% in patients younger and older than 75 years, respectively (P < 0.0001). It was higher in AKI than in non-AKI patients, both in the overall population (27% vs. 2%) and in the two age groups (25% vs. 2% and 29% vs. 5% in younger and older patients, respectively; P < 0.0001). The adjusted odds ratio of in-hospital mortality associated with AKI progressively decreased in parallel with increasing age decades (from 24.7 [95% CI 11.2-54.1] in patients <65 years to 3.9 [95% CI 1.6-9.7] in those >85 years)., Conclusions: In STEMI patients treated with pPCI, AKI incidence and in-hospital mortality steadily increase with age. However, the prognostic impact of AKI is progressively reduced as age increases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cardiogenic shock (CS) is the leading cause of in-hospital mortality in ST-segment elevation myocardial infarction (STEMI). Only limited data are available on the long-term outcome of STEMI patients with CS undergoing contemporary treatment. We aimed to investigate long-term mortality and its predictors in STEMI patients with CS and to develop a risk score for long-term mortality prediction., Methods and Results: We retrospectively included 465 patients with STEMI complicated by CS and treated with primary angioplasty and intra-aortic balloon pump between 2005 and 2018. Long-term mortality, including both in-hospital mortality and all-cause mortality following discharge from the index hospitalization, was the primary endpoint. The long-term mortality (median follow-up 4 (2.0-5.2) years) was 60%, including in-hospital mortality (34%). At multivariate analysis, independent predictors of long-term mortality were age (HR 1.41, each 10-year increase), admission left ventricular ejection fraction (HR 1.51, each 10%-unit decrease) and creatinine (HR 1.28, each mg/dl increase), and acute kidney injury (HR 1.81). When these predictors were pooled together, the area under the curve (AUC) for long-term mortality was 0.80 (95% CI 0.75-0.84). Using the four variables, we developed a risk score with a mean (cross-validation analysis) AUC of 0.79. When the score was applied to in-hospital mortality, its AUC was 0.79, and 0.76 when the score was applied to all-cause mortality following discharge., Conclusions: In STEMI patients with CS, the risk of death is still substantial in the years following the index event. A simple clinical score at the time of the index event accurately predicts long-term mortality risk.

Background: Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. The utility of serum alpha-fetoprotein (α-FP) in its detection is questionable. Over-expression and high circulating levels of insulin-like growth factor-II (IGF-II) were reported in tissue and in serum of patients with HCC. We investigated the diagnostic application of IGF-II in the diagnosis of HCC., Methods: Serum IGF-II and α-FP levels were measured in 178 patients (82 with HCC and 96 with liver cirrhosis) and in 30 healthy controls. Spearman test, non parametric combination test and confidence interval analysis were used for statistical evaluation of data., Results: The best cut-off values selected by ROC curves were 796 ng/ml for IGF-II and 132 ng/ml for α-FP. IGF-II mean values were higher in patients with HCC than in those with liver cirrhosis (LC) (p=0.0001) but lower in LC than in controls (p=0.0001). Serum IGF-II levels above cut-off were found in 22% of patients with HCC, in 9.3% of those with cirrhosis and in 20% of controls. α-FP serum levels >132 ng/ml were observed in 48% of HCC, in 3.1% of LC and in none of control group. By correlation study, serum IGF-II levels were significantly correlated with serum α-FP levels (r=0.427, p=0.0001) and with nodules' diameter (r=0.252, p=0.0130) but not with nodules' number (p>0.050). Finally, IGF-II showed lower sensitivity, specificity and predictive values than α-FP., Conclusion: Circulating IGF-II is not a useful marker for HCC. Further researches are however needed to evaluate its diagnostic accuracy before and after nutritional adjustment., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background/aims: The role of resistin, an adipocyte-secreted hormone, in insulin resistance and in inflammation is controversial. In chronic hepatitis C, insulin resistance, type 2 diabetes and liver steatosis are frequent and inconsistently correlated to circulating resistin levels. In this study we assessed if viral aetiology and host metabolic parameters influence serum resistin in patients with HCV- and HBV- related chronic hepatitis., Methodology: Serum resistin was measured by ELISA and correlated to viral aetiology, age, gender, BMI, HOMA-IR, liver steatosis, hepatitis staging and grading, blood glucose, triglycerides and cholesterol in 43 patients with chronic hepatitis C, in 16 with chronic hepatitis B and in 29 healthy controls., Results: In both groups of patients resistin was significantly higher than in controls, with higher values in HBV- than in HCV-patients (p = 0.0007). Resistin levels were correlated to aetiology and, inversely, to age (p = 0.026), diabetes (p = 0.036) and steatosis (p = 0.029). Multiple regression analysis showed that resistin concentration was dependent only on the aetiology of liver disease (p = 0.001)., Conclusions: In chronic viral hepatitis serum resistin levels are high and not associated with altered metabolic parameters or with the histological activity of the disease. The meaning of higher resistin in HBV- than in HCV- chronic hepatitis is unclear.

The phosphoinositide 3-kinase/Akt pathway is involved in the pathogenesis of several human cancers. In this study, the biological and prognostic value of phosphoinositide 3-kinase/Akt pathway dysregulation was assessed by immunohistochemistry in a well-characterized series of 72 patients with node-negative breast cancer with a long-term follow-up. Phosphorylated Akt and PTEN expression was reduced in 32% and 12.5% of the tumors, respectively. Phosphorylated Akt or PTEN status was not associated with the main clinicopathologic and biological parameters, whereas their expression was tightly related to their downstream targets cyclin D1 and p27(Kip1) which are involved in cell proliferation. Survival analysis showed a strong association between a shorter disease-free survival and the dysregulated expression of phosphorylated Akt (P = .036), PTEN (P = .003), p27(Kip1) (P = .008), and Ki67 (P = .0007), or the distinct subtypes of breast tumors (luminal, HER2 overexpressing, and basal-like; P = .03). Moreover, multivariate analysis using the Cox proportional-hazards regression model showed that PTEN and Ki67 were independent predictive factors of disease recurrence and that their simultaneous dysregulation strongly increased the hazards ratio of the patients with node-negative breast cancer (hazards ratio, 38.30; P = .0014). In conclusion, our results show that the dysregulation of the phosphoinositide 3-kinase/Akt/PTEN pathway is relevant to the prognosis in node-negative breast carcinoma and that the evaluation of key components of this pathway might be a useful tool to identify the patients with node-negative breast cancer at high-risk of disease recurrence.

Objective: To perform (i) an immunohistochemical investigation of cell proliferation, apoptosis, angiogenesis, and malignancy markers in 15 functioning and 15 nonfunctioning thyroid adenomas, and in normal adjacent tissue, and (ii) a genetic analysis of thyroid-stimulating hormone receptor (TSH-r), Gsalpha, and RAS mutations in the same group of adenomas, in order to describe their expression within tissues and to correlate them with the hormonal functioning., Design: Thirty patients who underwent surgery for a solitary thyroid nodule were included in the study. Adenomas and normal adjacent tissues were evaluated by immunohistochemistry using the following antibodies: MIB-1 for proliferative activity, bcl-2 and mutant p53 for apoptosis control, vascular endothelial growth factor-A (VEGF-A) for angiogenic activity, and galectin-3 as a marker for malignancy. To calculate microvascular density, "hot spots" were selected and defined by cells positive for CD34 staining. Genetic analysis for TSH-r, Gsalpha, and H-, K-, and N-RAS mutations was performed on adenoma specimens., Main Outcomes: Our results evidenced that a proportion of both functioning and nonfunctioning adenomas showed immunohistochemical phenotypes similar to normal adjacent tissue. No differences were found between functioning and nonfunctioning thyroid adenomas with regard to the expression of markers associated to angiogenesis (VEGF-A, microvascular density) and apoptosis control (mutant p53, bcl-2). All adenomas resulted negative for galectin-3 immunostaining. MIB-1 was the only marker showing a substantial difference of expression between the two groups of adenomas. TSH-r mutations were found in 12 out of 15 functioning adenomas, whereas the absence of Gsalpha and H-, K-, and N-RAS mutations was demonstrated in all adenomas., Conclusions: Our data suggest that the differences between functioning and nonfunctioning thyroid adenomas are restricted to the genetic mutations of the TSH-r, to the hormonal status of tumors, and to the proliferative activity, not involving markers of apoptosis control and angiogenesis.

Aim: The utility of serum alpha-fetoprotein (alpha-FP) in the detection of hepatocellular carcinoma (HCC) is questionable. Very high circulating levels of nociceptin/orphanin FQ (N/OFQ), a ligand for a novel opioid receptor, have recently been reported in HCC. The aim of this study was to assess the role of plasma N/OFQ in the diagnosis of HCC arising in patients with liver cirrhosis., Methods: Plasma N/OFQ levels were measured by ELISA in 58 patients (28 HCC and 30 liver cirrhosis) and in 25 healthy controls. The values were correlated with clinical and laboratory features including alpha-FP. Spearman index, biserial correlation coefficient, non parametric combination (NPC) test and discriminant stepwise analysis were used for statistical evaluation of data., Results: The upper normal limit of nociceptin was 122 pg/mL. Plasma levels above this cut-off were found in 21.4% of patients with HCC, in 23.3% of those with cirrhosis and in 8% of healthy subjects. alpha-FP serum levels > 200 ng/mL were found in 46.4% of the patients with HCC and in none of those with cirrhosis. No correlation was found between N/OFQ levels and any of the clinical and laboratory features, including alpha-FP. By NPC test, HCC and cirrhotic patients were different with regard to alpha-FP (P = 0.000) but not in terms of nociceptin (P = 0.595). By point biserial correlation, HCC presence was positively correlated with alpha-FP (rpb = 0.52, P = 0.000) but not with N/OFQ (rpb = 0.16, P = 0.157). In a discriminant analysis, alpha-FP was significant in the Wilks test (Y = -0.709 + 0.03 alpha-FP) and properly classified 81% of all patients and 61% of HCC. N/OFQ had lower sensitivity, specificity and predictive values than alpha-FP., Conclusion: Nociceptin is increased in patients with chronic liver disease, independently of the presence of HCC, although the underlying mechanism has yet to be clarified. We conclude it is not a useful marker for HCC.

Spa therapy is an ancient approach to degenerative diseases such as osteoarthritis, but until today this tradition has been predominantly empiric and intuitive and few studies have focused on the biological changes derived from this treatment. We assessed the clinical efficacy and variations in amino acid concentrations in serum samples from patients with knee osteoarthritis who underwent spa therapy and put forward an explanation of their role in clinical improvement. Thirty-one patients with knee osteoarthritis who underwent spa therapy underwent a clinical evaluation, and serum amino acid levels were assayed before and after a cycle of balneotherapy and mud-pack therapy. The thermal treatments were carried out in Sciacca. Analysis of the data showed a significant reduction in pain and improvement in joint motility. Serum concentrations of tryptophan, cysteine and citrulline were significantly higher than at baseline. No significant differences were observed in serum levels of the remaining free amino acids. The results of this study confirm the efficacy of spa therapy in the treatment of osteoarthritis. A possible role for changes in serum amino acid concentration is discussed.

Background/aims: Thrombopoietin is a thrombopoietic factor mainly synthesized in the liver. Its production is regulated by the mass of megakaryocytes and platelets. Impaired production of thrombopoietin may be responsible for thrombocytopenia in chronic liver disease., Methodology: We studied thrombopoietin serum concentration in 68 patients with chronic liver disease of various degrees (39 with thrombocytopenia), in 5 patients with thrombocytopenia due to hematological disease, and in 27 healthy controls., Results: Thrombopoietin concentration was higher in patients with liver disease than in controls. Patients with hematological disease had much higher thrombopoietin concentration than patients with liver disease. Among patients with liver disease and thrombocytopenia, thrombopoietin concentration was higher in cirrhosis than in chronic hepatitis. A negative correlation was found between platelet counts and spleen size and between thrombopoietin concentration and spleen size. No correlation was found between thrombopoietin concentration and liver disease severity., Conclusions: Patients with liver disease and thrombocytopenia have serum thrombopoietin concentration higher than normal controls. It seems therefore that the liver, even seriously diseased, maintains the ability to produce thrombopoietin. In the liver patients the number of circulating platelets and the serum levels of thrombopoietin are inversely correlated with the size of the spleen suggesting that thrombopoietin, although normally produced, might be turned over in platelets sequestrated in the spleen.

Background/aims: We retrospectively evaluated the long-term efficacy of interferon retreatment in patients with chronic hepatitis C, who did not have a sustained response to a 1st cycle of treatment., Methodology: Sixty-six patients, 43 non-responder and 23 relapser to alpha interferon treatment, were retreated with alpha interferon, 6 MU thrice weekly for 12 months. Response was defined as negative HCV viremia. Responders underwent long-term follow-up (27-43 months)., Results: The response rates were 14% and 35% at the end of retreatment, 7% and 22% at 6 months, and 2% and 13% at long-term follow-up in non-responders and relapsers respectively. The outcome of retreatment was not statistically influenced by age, cirrhosis, viral genotype, dose and duration of previous treatment., Conclusions: Interferon retreatment, for sustained viral eradication, is not effective in non-responders and useful in few relapsers. Whereas, retreatment could prove effective in slowing down the activity of the disease and reducing the incidence of hepatocarcinoma, since some relapses occur late during the follow-up. Therefore, retreatment should be confined to relapsers with contraindications to new more efficient therapeutic strategies.

Background/aims: The impact of the treatment with interferon (IFN) on the natural history of chronic hepatitis C is not defined. The aim of this study was to evaluate the long term effect of the treatment in patients with chronic hepatitis C., Methodology: In 31 patients with chronic hepatitis C (9 with cirrhosis) consecutively treated with recombinant alpha 2a interferon (r alpha 2a IFN), the evolution of the disease at 10 years from the therapy was evaluated by means of upper endoscopy, liver ultrasonography (US), liver function tests and hepatitis C virus (HCV) viremia., Results: Among 10/31 patients previously classified as responders, only 1 has signs of evolution to cirrhosis; HCV-RNA is still present in 2. Among 21 non-responder patients, 5 developed hepatocarcinoma (HCC) and 4 died during the follow-up; HCV-RNA is present in all the patients still alive. The 6 patients already cirrhotic when treated have clinical signs of progression to Child class B and C. The biochemical, ultrasonographical and endoscopical evaluation shows onset of cirrhosis in 7 of the others., Conclusions: Patients with chronic hepatitis C who respond to treatment with interferon have good outcome and rare evolution to cirrhosis. The treatment does not seem to influence the natural history of the disease in non-responders.

Background/aims: Enhanced hepatocellular display of class I HLA antigens together with rising serum beta-2-microglobulin (a subunit of class I HLA molecule) and transaminases is reported in patients with chronic hepatitis B during treatment with interferon as an index of immune lysis of virus infected cells., Methodology: We studied class I HLA antigens and beta-2-microglobulin display in the livers of 23 patients with chronic hepatitis C before and after a 12 month treatment with recombinant alpha interferon. Beta-2-microglobulin serum values were monitored. In all the patients before treatment, class I HLA antigens and beta-2-microglobulin were diffusely displayed in the bile duct epithelium, in the sinusoidal lining cells, in approximately 50% of the inflammatory cells and in the hepatocyte membrane with marked staining in the areas of periportal and lobular necrosis., Results: At the end of the treatment, class I HLA antigens and beta-2-microglobulin were no longer or only faintly detectable in the hepatocytes of 12 patients who showed clinical and histological improvement. The immunohistochemical pattern was unchanged in the 11 patients who did not respond to the therapy. Baseline serum beta-2-microglobulin values were high in all the patients and decreased significantly only in the group of responders. No peaks of transaminases were registered., Conclusions: The disappearance or reduction of HLA hepatocellular display without acute increase of serum beta-2-microglobulin values and transaminases during successful treatment with interferon in chronic hepatitis C suggests a clearance of the virus due to direct antiviral rather than immunologically mediated mechanism.

Viral infection may play a role in alcoholic liver disease with histological features of chronic active hepatitis (CAH). Human leucocyte antigen (HLA) hepatocellular display is supposed to allow HLA-restricted T-lymphocyte cytotoxicity in chronic viral hepatitis. We studied the presence of serum anti-hepatitis C virus (HCV) antibodies, the hepatic HLA display and the composition of the mononuclear cell infiltrate in 16 patients with alcoholic liver disease and histological features of CAH and in 11 patients with alcohol-related degenerative changes. All patients were negative for hepatitis B virus (HBV) markers. Anti-HCV were tested by microplate ELISA. Class I HLA A, B, class II HLA DR, lymphocytes pan T, T helper/inducer, T suppressor/cytotoxic, B, and K NK cells were stained on liver cryostat sections by monoclonal antibodies and double indirect immunoperoxidase. Anti-HCV were present in all the patients with features of CAH and absent in those with only degenerative changes. In livers with features of CAH the mononuclear cell infiltrate consisted largely of T lymphocytes with marked prevalence of suppressor/cytotoxic cells in periportal and lobular areas. K NK cells were rare. Class I HLA, diffusely displayed on bile duct epithelium and on sinusoidal cells, also appeared on liver cells in the areas of periportal and lobular necrosis, namely on the hepatocytes in close contact with suppressor/cytotoxic T cells. In livers with only degenerative changes class I HLA were diffusely displayed on bile duct epithelium and on sinusoidal cells but absent on the hepatocytes. In all the specimens HLA DR antigens were expressed on sinusoidal and inflammatory cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Sera from 619 HBsAg+ subjects living in eastern Sicily, consecutively collected from 1975-1985, were tested for markers of delta virus (HDV) infection: delta antigen (HDAg), antibodies to delta (anti-HDIg), and also for antibodies to HBcore of IgM type (anti-HBcIgM) and for the system HBe-anti-HBe. The subjects included 210 asymptomatic carriers, 238 patients with acute hepatitis and 171 patients with chronic liver disease. HDAg was not found in any of the samples. Anti-HD was found in 28/171 (16.3%) patients with chronic liver disease, in 13/210 (6%) asymptomatic HBsAg carriers and in 13/238 (5.4%) patients with acute hepatitis. None of our patients were drug addicts. One had a history of blood transfusion, and nine came from the same family unit. The prevalence of HDV infection in eastern Sicily is lower than in other areas of Sicily possibly because of the lower percentage of HBsAg carriers in the local population. Parenteral transmission of HDV does not seem to play a major role in our area, while the familial clustering suggests close body contact as an important way of spread.

Anti-HBV core IgM antibodies (anti-HBc IgM) were tested by RIA in the sera from 269 patients with acute viral hepatitis (AVH), from 39 patients with chronic HBSAg+ hepatitis (CH) at various stage of evolution, in 41 asymptomatic HBsAg carriers and in 30 healthy volunteers. Anti-HBc IgM were found in 100/108 HBsAg+ AVH, in 6/161 HBsAg--AVH, in 9/39 with CH and only 1 asymptomatic HBsAg carrier. Among the chronic patients with anti-HBc IgM, 3 were HBeAg+ and 6 were anti-HBe+. The test of anti-HBc IgM results useful in the early aetiological diagnosis of acute hepatitis since it is always positive in HBV acute hepatitis even in the subjects who early seroconvert to anti-HBs; the absence of anti-HBc IgM in the HBsAg+ acute hepatitis suggests other overinfecting agents. The presence of anti-HBc IgM in CH seems not to be related to an active viral replication.

The parameters in antibody-positive with LAS/ARC and antibody negative drug-users have been studied. The results show that in the first group the lymphocyte profile and in vitro immunoglobulin production are greatly affected. In the second group only modifications about activation markers and PWM induced B lymphocyte differentiation are present.

The prevalence of the anti-HBc antibodies was studied in 54 patients with chronic liver disease and in a group of controls pair-matches. The meaning of the anti-HBc antibodies titer in the patients HBsAg negative is discussed. From our data, obtained by Radioimmunoassay, anti-HBc titers I:I000 seem to indicate an ongoing or recent viral replication, being probative, even in the absence of the HBsAg marker, for the viral etiology.

HBeAg and anti-HBe were tested by RIA (Abbott Kits) in 53 patients (38 HBsAg +) with acute viral hepatitis (AVH), in 27 patients (5 HBsAg +) with chronic active hepatitis (CAH), in 54 (8 HBsAg +) with cirrhosis, in 32 (17 HBsAg +) undergoing haemodialysis, in 6 HBsAg carriers and in 45 controls. Most of the patients with HBsAg + AVH were HBeAg + in the first week and showed seroconversion to anti-HBe within the fourth week of the illness. Two from the four patients still HBeAg + in the fourth week seroconverted later on and clinically recovered, one is still HBsAg +/HBeAg + in the seventh week and one developed CAH HBsAg +/HBeAg +. High prevalence of HBeAg was found in the haemodialysed (94%) and in the patients with CAH (80%) while anti-HBe was more frequent in the HBsAg carriers (100%) and in the cirrhotics (62,5%). Among the patients HBsAg-, none was HBeAg + while 18% with CAH, 21,7% with cirrhosis, 26,6% of the haemodialysed and 4% of the controls were anti-HBe +. Our data, relating to AVH, are similar to those referred in the literature, but show conversely high prevalence of anti-HBe in CAH and in cirrhosis.

Little is known from the literature about the epidemiology of non A - non B hepatitis (NANB/H) in childhood. Aim of this study was to assess the prevalence of NANB/H in a consecutive series of children with acute viral hepatitis hospitalized over an one year's period. Thirty children, 9 females, aged 3-12 years, were studied. Serial blood samples were tested for HBsAg, anti-HBs, anti-HBc, anti-HAV (Abbott RIA), anti-HAV-IgM (Absorption Staph. aureus protein A), anti-EBV (Immunofluorescence), anti-CMV, anti-Herpes s. virus (complement fixation). The diagnosis of NANB/H was based on the absence of these markers. Nineteen patients (63,3%) had type A, and 5 (16,6%), had type B hepatitis. One child showed antibodies anti-Herpes with rising titer and 5 (16.6%), 2 females, were considered suffering from NANB/H. None of these patients had been injected or haemotransfuded; all but one came from rural ambient and two from the same family. Two children had an anicteric course. The illness lasted less than 30 days in all but one, who showed three peaks of transaminases and recovered after 70 days. These data show a prevalence of NANB/H in childhood greater than that elsewhere reported, while the absence of injections suggests a way of infection other than parenteral.

As high levels of Prostaglandins E2 were observed in several gastric diseases, the Authors determined the PGE2 levels in gastric cancer patients without recurrences, in pre and post-operative period. PGE levels were correlated with cancer progression and their significance as tumoral markers was also assessed.