Infections ACLF Death Different clinical courses of acutely decompensated cirrhosis Pre-ACLF Unstable decompensated cirrhosis Stable decompensated cirrhosis 0 90 180 270 360 Days Highlights Patients with acutely decompensated cirrhosis without ACLF develop 3 different clinical courses. Patients with pre-ACLF develop ACLF within 90 days and have high systemic inflammation and mortality. Patients with unstable decompensated cirrhosis suffer from complications of severe portal hypertension. Patients with stable decompensated cirrhosis have less frequent complications and lower 1-year mortality risk.

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Summary Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The MetlHGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P=0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P<0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

Digital ulcers (DU) at the hands are one of the more frequent and severe complications in systemic sclerosis. Data on their prevalence and distribution in the different subsets of disease are variable in the literature. We studied the frequency of DU in a cohort of 333 scleroderma patients followed in the last 10 years in our Unit. DU have been recorded in 133 patients (39,9%), more frequently in males, in patients with cutaneous diffuse form of disease and in patients with anti-Scl70 ANA specificity. Complications of DU have been observed in 12,3% of cases. Surgery of the hands has been required in 8,7% of patients. The more effective treatment of DU are i.v. prostanoids, performed usually in day hospital, with high costs for the National Health Service. Recently the efficacy of bosentan, an oral receptor antagonist of endothelin, has been demonstrated, thus opening new perspectives in the treatment of DU in systemic sclerosis