Post-recurrence survival in hepatocellular carcinoma after percutaneous radiofrequency ablation

Background

Overall survival in hepatocellular carcinoma patients treated with percutaneous radiofrequency ablation is influenced by both recurrence and successive treatments. We investigated post-recurrence survival after radiofrequency ablation.

Methods

Data on 103 early/intermediate patients initially treated with radiofrequency ablation and followed for a median of 78 months (range 68–82) were retrospectively analysed. If intrahepatic disease recurrence occurred within or contiguous to the previously treated area it was defined as local, otherwise as distant; recurrence classified as Barcelona Clinic Liver Cancer stage C was defined by neoplastic portal vein thrombosis or metastases.

Results

A total of 103 patients were included (82.5% male; median age 70 years, range 39–86). During follow-up, 64 recurrences were observed. Median overall survival was 62 months (95% confidence interval: 54–78) and survival rates were 97%, 65% and 52% at 1, 4 and 5 years, respectively. Median post-recurrence survival was 22 months (95% confidence interval: 16–35). Child–Pugh score, performance status, sum of tumour diameters at recurrence and recurrence patterns were independent predictors of post-recurrence survival.

Conclusions

In patients with hepatocellular carcinoma after radiofrequency ablation, clinical and tumour parameters assessed at relapse, in particular the type of recurrence pattern, influence post-recurrence survival.     

IsdC from Staphylococcus lugdunensis Induces Biofilm Formation under Low-Iron Growth Conditions

Staphylococcus lugdunensis is a coagulase-negative staphylococcus that is a commensal of humans and an opportunistic pathogen. It can cause a spectrum of infections, including those that are associated with the ability to form biofilm, such as occurs with endocarditis or indwelling medical devices. The genome sequences of two strains revealed the presence of orthologues of the ica genes that are responsible for synthesis of poly-N-acetylglucosamine (PNAG) that is commonly associated with biofilm in other staphylococci. However, we discovered that biofilm formed by a panel of S. lugdunensis isolates growing in iron-restricted medium was susceptible to degradation by proteases and not by metaperiodate, suggesting that the biofilm matrix comprised proteins and not PNAG. When the iron concentration was raised to 1 mM biofilm formation by all strains tested was greatly reduced. A mutant of strain N920143 lacking the entire locus that encodes iron-regulated surface determinant (Isd) proteins was defective in biofilm formation under iron-limited conditions. An IsdC-null mutant was defective, whereas IsdK, IsdJ, and IsdB mutants formed biofilm to the same level as the parental strain. Expression of IsdC was required both for the primary attachment to unconditioned polystyrene and for the accumulation phase of biofilm involving cell-cell interactions. Purified recombinant IsdC protein formed dimers in solution and Lactococcus lactis cells expressing only IsdC adhered to immobilized recombinant IsdC but not to IsdJ, IsdK, or IsdB. This is consistent with a specific homophilic interaction between IsdC molecules on neighboring cells contributing to accumulation of S. lugdunensis biofilm in vivo.     

Molecular events underlying interleukin‐6 independence in a subclone of the CMA‐03 multiple myeloma cell line

We explored the molecular mechanisms involved in the establishement of CMA‐03/06, an IL‐6‐independent variant of the multiple myeloma cell line CMA‐03 previously generated in our Institution. CMA‐03/06 cells grow in the absence of IL‐6 with a doubling time comparable with that of CMA‐03 cells; neither the addition of IL6 (IL‐6) to the culture medium nor co‐culture with multipotent mesenchymal stromal cells increases the proliferation rate, although they maintain the responsiveness to IL‐6 stimulation as demonstrated by STAT1, STAT3, and STAT5 induction. IL‐6 independence of CMA‐03/06 cells is not apparently due to the development of an autocrine IL‐6 loop, nor to the observed moderate constitutive activation of STAT5 and STAT3, since STAT3 silencing does not affect cell viability or proliferation. When compared to the parental cell line, CMA‐03/06 cells showed an activated pattern of the NF‐κB pathway. This finding is supported by gene expression profiling (GEP) analysis identifying an appreciable fraction of modulated genes (28/308) in the CMA‐03/06 subclone reported to be involved in this pathway. Furthermore, although more resistant to apoptotic stimuli compared to the parental cell line, CMA‐03/06 cells display a higher sensibility to NF‐κB inhibition induced by bortezomib. Finally, GEP analysis suggests an involvement of a number of cytokines, which might contribute to IL‐6 independence of CMA‐03/06 by stimulating growth and antiapoptotic processes. In conclusion, the parental cell‐line CMA‐03 and its variant CMA‐03/06 represent a suitable model to further investigate molecular mechanisms involved in the IL‐6‐independent growth of myeloma cells. © 2013 Wiley Periodicals, Inc.     

Identification and management of invasive mycoses in internal medicine: a road-map for physicians

Invasive mycoses are a rising problem, not only in traditional categories of patients like hematologic or neutropenic ones, but also in elderly non-neutropenic patients admitted to internal medicine wards. Patients being admitted to medical wards are usually older, have multiple comorbidities, e.g., liver cirrhosis or chronic obstructive respiratory disease, may be malnourished or receive peripheral or total parenteral nutrition, and frequently are undergoing chronic corticosteroid therapy, chemotherapy for cancer or monoclonal antibodies for autoimmune diseases. Such risk factors may be contemporarily present in a single patient increasing the risk for the development of invasive mycoses. Diagnosis of candidemia and invasive aspergillosis is particularly difficult in patients hospitalized on medical wards, since symptoms and signs have low specificity, and most diagnostic tests have been only validated in neutropenic hematologic patients, but not in those without neutropenia. Both candidemia and invasive aspergillosis carry significant morbidity and mortality. The aim of this paper is to provide a simple guide to physicians for a prompt identification and treatment of patients with possible or suspected invasive mycoses.     

The association among food addiction,binge eating severity and psychopathology in obese and overweight patients attending low-energy-diet therapy

Several studies have shown that food addiction (FA) is strongly related with psychopathology. However, this relationship may be partly mediated by the presence and severity of binge eating. The aim of the current study was to assess the strength of the association between FA and psychopathology, and whether this relationship was mediated by the presence and severity of binge eating. Participants were 112 patients seeking weight loss interventions. All the participants were administered the Yale Food Addiction Scale (YFAS), The Symptom Check list-90-R (SCL-90), and the Binge Eating Scale (BES). Thirty-eight (33.9%) individuals were diagnosed as having FA. FA severity was strongly associated with binge eating, whereas both FA and binge eating were positively and moderately associated with psychopathology. A mediational model analyzing direct and indirect (through the mediating role of binge eating) effects of FA on psychopathology indicated that the relation between FA and psychopathology was fully mediated by the severity of binge eating. This finding suggests that FA may contribute to the development of psychopathology through its effect on binge eating.     

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.     

Intra-aortic balloon pumping recruits graft flow reserve by lowering coronary resistances

Background

The intra-aortic balloon pump (IABP) is used worldwide as an anti-ischemic strategy and to reduce myocardial workload. However, whether IABP augments coronary flow after coronary bypass via a passive increase in diastolic pressure or an active response of the coronary bed remains uncertain.

Methods

We analyzed transit-time flow measurements and the contemporary changes in coronary resistances obtained during 1:1 IABP and during its cessation in 144 consecutive patients receiving prophylactic IABP before isolated coronary artery bypass grafting (n = 340 graft segments).

Results

Normally functioning grafts showed lower coronary resistances, greater percentage decrease in resistance, and greater increases in average maximum diastolic and mean flow during 1:1 IABP compared with IABP cessation (P < .001). Arterial and sequential saphenous vein grafts showed better flowmetry and greater reductions in coronary resistances compared with single venous grafts. Accordingly, graft flow reserve (defined as mean flow during 1:1 IABP/mean flow with IABP off) was recruited (graft flow reserve > 1) during 1:1 IABP in all normally functioning grafts, with higher values in single arterial or sequential saphenous vein grafts than in single venous grafts (both P < .001). Coronary resistances were higher in 7 failed grafts versus normal-functioning grafts at baseline; these did not decrease during 1:1 IABP and showed worse transit-time flow results.

Conclusions

IABP recruits graft flow reserve by lowering coronary resistance in functioning grafts. Arterial and sequential venous grafts showed greater reduction in coronary resistance compared with single saphenous grafts.