Hepatocellular carcinoma (HCC) represents a worldwide health matter with a major care burden, high prevalence, and poor prognosis. Its pathogenesis mainly varies depending on the underlying etiological factors, although it develops from liver cirrhosis in the majority of cases. This review summarizes the role of the most interesting soluble factors as biomarkers for early diagnosis and as recommended targets for treatment in accordance with the new challenges in precision medicine. In the premalignant environment, inflammatory cells release a wide range of cytokines, chemokines, growth factors, prostaglandins, and proangiogenic factors, making the liver environment more suitable for hepatocyte tumor progression that starts from acquired genetic mutations. A complex interaction of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory cytokines (TGF-α and -β), pro-angiogenic molecules (including the Angiopoietins, HGF, PECAM-1, HIF-1α, VEGF), different transcription factors (NF-kB, STAT-3), and their signaling pathways are involved in the development of HCC. Since cytokines are expressed and released during the different stages of HCC progression, their measurement, by different available methods, can provide in-depth information on the identification and management of HCC.

We aimed to investigate the role of positron emission computed tomography (PET/CT) with ¹⁸F-choline for predicting the outcome of metastatic castration-resistant prostate cancer (mCRPC) submitted to treatment with Radium-223 (²²³Ra-therapy). Clinical records of 20 mCRPC patients submitted to PET/CT with ¹⁸F-choline before ²²³Ra-therapy were retrospectively evaluated. The following PET-derived parameters were calculated: number of lesions, maximum and mean standardized uptake values (SUVmax, SUVmean), lean body mass corrected SUV peak (SULpeak), metabolic tumor volume (MATV), and total lesion activity (TLA). After ²²³Ra-therapy, all patients underwent regular follow-up until death. The predictive power of clinical and PET-derived parameters on overall survival (OS) was assessed by Kaplan–Meier analysis and the Cox proportional hazard method. All the patients showed ¹⁸F-choline-avid lesions at baseline PET/CT. Among the enrolled subjects, eleven (55%) completed all the six scheduled cycles of ²²³Ra-therapy; seven (35%) were responders according to imaging and biochemical parameters. Mean OS was 12.7 ± 1.4 months: by Kaplan–Meier analysis, number of lesions, PSA level and TLA were significantly correlated with OS. In multivariate Cox analysis, TLA remained the only significant predictor of survival (p = 0.003; hazard ratio = 7.6, 95% confidence interval = 1.9–29.5 months). ¹⁸F-choline PET may be useful for patients’ stratification before ²²³Ra-therapy. In particular, high metabolically active tumor burden (i.e., TLA) was predictive of poor outcome.

The antibody-related immune response is mediated by immunoglobulins (Igs), soluble circulating glycoproteins produced by activated B cells that, upon the recognition of specific epitopes on pathogen surfaces, activate, proliferate, and differentiate into antibody-secreting plasma cells. Although the antibodies are effectors of the humoral immune adaptive response, their overproduction in response to a dysregulated proliferation of clonal plasma cell production in tumoral conditions (i.e., multiple myeloma), enriches the serum and urinary matrices, assuming the crucial role of biomarkers. Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the expansion and accumulation of clonally activated plasma cells in bone marrow, determining the release of high amounts of monoclonal component (MC) that can be detected as intact immunoglobulin (Ig), immunoglobulin fragments, or free light chains (FLCs). The importance of detecting biomarkers for the diagnosis, monitoring, and prognosis of diseases is highlighted by the international guidelines that recommend specific assays for the analysis of intact Igs and FLC. Moreover, a developed assay called Hevylite^® allows for the quantification of immunoglobulins that are both involved (iHLC) and not involved (uHLC) in the tumor process; this is a fundamental aspect of following up the patient’s workup and evaluating the progression of disease, together with the treatments response. We here summarize the major points of the complex scenario involving monoclonal gammopathies and MM clinical management in view of advantages derived for the use of Hevylite^®.

Background Biosimilar drugs have a similar, but usually not inferior although not hidentical effects of old registred drugs. Safety is hidentical to old registred drug. Aims Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha is not inferior to erythropoietin alpha in terms of safety, efficacy and costs. Methods This study is a dicentric, nonrandomized, retrospective study. Between july 2008 and june 2012, 92 patients affected by refractory anemia were studied. Median follow-up was 22 months (R3-34). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In both groups patients received liposomal iron (Sideral^®) 14 mg, 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median age was 70 years (R63-75), M/F: 18/28; in group B median age was 64 years (R60-70), M/F: 25/21. IPSS was low in 30 patients and int-1 in 13 patients in group A, and low in 32 patients and int-1 in 11 patients, in group B. Patients with 5q- were excluded from this study. Median level of haemoglobin was 8.5 g/dl in group A (R8-11) and 9.2 g/dl (R8.5-11.5) in group B. Results Group A patients increased Hb level of 1 g/dl after a median time of 5 weeks (R4-9) and after a median time of 4 weeks (R3-8) in group B. No relevant side effects were observed in both groups. Erythropoietin alpha was reduced in group A because Hb achieved a level > 12g/dl after a median of 12 weeks (R 4-18). Biosimilar erythropoietin alpha was reduced in group B because Hb achieved a level > 12g/dl after a median of 10.5 weeks (R 3-16). In group A maintenance dose was administered with a median of every two weeks (2-4), In group B maintenance dose was administered with a median of every three weeks (2-5). Median cost for every month of erythropoietic therapy was 1536 euros/month (R1240-1850) in group A and 1354 euros/month (R954-1550) in group B. Five patients need transfusion support in group A and seven patients need transfusion support in group B Summary/conclusion Biosimilar erythropoietin alpha plus liposomal iron (Sideral^®) and B12 and folates support seems to be safe, feasible, probably equally cost-effective and substantially not inferior to classical erythropoietin alpha support in patients affected by refractory anemia. This study needs confifrmation on a larger cohort of patients.

Background: Interpreting low-grade of high-sensitivity cardiac troponin I (hs-TnI) concentrations reflecting myocardial injury in asymptomatic populations remains clinically uncertain. This study characterized predefined sex-specific hs-TnI categories in apparently healthy blood donors and compared them with conventional cardiovascular assessment methods. Methods: We performed a cross-sectional analysis of 292 blood donors (77 women, 26.4%; 215 men, 73.6%; age range, 40–65 years). Hs-TnI was measured using the Abbott ARCHITECT STAT High Sensitive Troponin-I assay and categorized according to predefined sex-specific thresholds. Categories were compared with clinical variables, cholesterol/HDL-ratio categories, Framingham Risk Score categories, and SCORE2 in eligible participants (n = 287). Additional analyses included non-parametric comparisons, Spearman correlations, agreement statistics, and multivariable models. A sensitivity analysis used sex-specific empirical hs-TnI tertiles, and effect sizes with bootstrap 95% confidence intervals were reported for key comparisons. Results: Hs-TnI categories were low in 253 subjects (86.6%), intermediate in 17 (5.8%), and elevated in 22 (7.5%). Hs-TnI was markedly skewed, especially in the elevated category (median, 21.5 ng/L; IQR, 15.25–36.0; range, 11–199). Agreement with conventional categories was low, with weighted kappa values of 0.035 versus Framingham, −0.008 versus cholesterol/HDL-ratio categories, and 0.076 versus SCORE2. Conventional cardiovascular variables showed limited independent association with intermediate/elevated hs-TnI categories. Tertile-based sensitivity analyses yielded weighted kappa values of 0.045 versus Framingham, 0.033 versus cholesterol/HDL-ratio categories, and 0.037 versus SCORE2. Conclusions: In selected blood donors, predefined hs-TnI categories showed limited concordance with conventional cardiovascular scores, exploratory-wise suggesting a distinct phenotype of low-grade myocardial injury.