Epstein-Barr viral load, interleukin-6 and interleukin-10 levels in post-transplant lymphoproliferative disease: a nested case-control study in a renal transplant cohort

The possible correlation among Epstein-Barr virus (EBV) load, interleukin-6 (IL-6) and interleukin-10 (IL-10) levels has become an attractive issue and can provide a useful tool for diagnosis and monitoring of patients at risk for post-transplant lymphoproliferative disease (PTLD) development. At the time of diagnosis of PTLD, 11 patients were prospectively enrolled and 55 nested controls were selected from a 1800 renal transplant cohort. Real-time polymerase chain reaction (PCR) was used to quantify EBV load in peripheral blood mononuclear cells (PBMC). Serum IL-6 and IL-10 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The median EBV load of PTLD cases was 17400 copies/10(6) PBMC, statistically different from controls (P=0.001). The median IL-6 level of PTLD cases was not different from controls (P=0.079). However, median IL-10 levels showed a significant difference in both groups (P < or = 0.001). The receiver-operating characteristic (ROC) curve analysis was applied to estimate the IL-10 cut-off value predictive of PTLD development. We found that 73.5 pg/ml has high sensitivity (1.00) and specificity (0.85). Also, Pearson's analysis showed a strong correlation between EBV load and serum IL-10 concentration (P < or = 0.001). This nested case-control study demonstrates that EBV load at diagnosis of PTLD correlates with IL-10 levels, and that monitoring of IL-10 can provide a less expensive and less time-consuming tool for PTLD diagnosis and close follow-up of patients at risk. Furthermore, we were able to define a cut-off value of IL-10 mostly predictive of PTLD development in this cohort. Our data suggest that serial measurements prior to PTLD development must be carried out to validate our hypothesis.     

The absence of CD20 messenger RNA in recurrent cutaneous B-cell lymphoma following rituximab therapy

BACKGROUND: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported. METHODS: Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available. RESULTS: Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology. CONCLUSIONS: Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.     

Endocarditis due to glycopeptide-intermediate Staphylococcus aureus: case report and strain characterization

We report a case of infective endocarditis due to vancomycin-intermediate Staphylococcus aureus (VISA) that did not respond to high doses of vancomycin. Initial vancomycin MIC of the last isolate recovered from blood was 8 micro g/mL, but could be induced up to 32 micro g/mL by consecutive growing with vancomycin. Clinical response was only accomplished when linezolid was included in therapy.     

Protective role of tauroursodeoxycholate during harvesting and cold storage of human liver: a pilot study in transplant recipients

BACKGROUND: Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. Tauroursodeoxycholic acid (TUDCA), a natural amidated hydrophilic bile salt, protects from cholestasis and hepatocellular damage in a variety of experimental models, as well as from ischemia-reperfusion injury. We investigated in the human liver transplantation setting the effect of the addition of TUDCA at time of liver harvesting and cold storage on the intra- and postoperative enzyme release and liver histopathology at the end of cold storage, at reperfusion, and 7 days after transplantation. METHODS: Eighteen patients undergoing elective liver transplantation were studied, including 6 serving as controls. In six patients, TUDCA was added to the University of Wisconsin solution used during harvesting and cold storage, to reach final concentrations of 2 mM. In three of these patients, TUDCA (3 g) was infused in the portal vein of the donor before organ explantation; in the other three cases, TUDCA was given through both routes. RESULTS: The use of TUDCA did not cause adverse events. The release of aspartate aminotransferase in the inferior vena cava blood during liver flushing was significantly lower (P=0.05) in TUDCA-treated than in control grafts, as were cytolytic enzyme levels in peripheral blood during the first postoperative week (P<0.02). At electron microscopy, an overt endothelial damage (cytoplasmic vacuolization, cell leakage, and destruction with exposure of hepatocytes to the sinusoidal lumen) was invariably found in control grafts, both at reperfusion and at day 7 after transplant. These features were significantly ameliorated by TUDCA (P<0.001). Several ultrastructural cytoplasmic abnormalities of hepatocytes were seen. Among these, damage to mitochondria matrix and crystae was significantly reduced in TUDCA-treated versus control grafts (P<0.01). Mild to severe damage of bile canaliculi was a constant feature in control biopsies, with dilatation of canalicular lumen and loss of microvilli. Both these abnormalities were markedly ameliorated (P<0.001 by TUDCA). The best preservation was observed when TUDCA was given through both routes. CONCLUSIONS: The use of TUDCA during harvesting and cold storage of human liver is associated with significant protection from ischemia-reperfusion injury. The clinical significance of this findings must be studied.     

Intravenous ciprofloxacin for the treatment of severe infections

Intravenous ciprofloxacin at a daily dosage of 400 mg divided in two doses was administered to 19 patients with severe infections caused by ciprofloxacin-susceptible bacteria. These infections included: 11 surgical would infections, 5 soft tissue infections, 2 respiratory tract infections, 1 urinary tract infection. The offending pathogens were: 8 coagulase-negative staphylococci, 3 Staphylococcus aureus, 3 Pseudomonas aeruginosa, 2 Proteus spp., 1 Escherichia coli, 1 Branhamella catarrhalis, 1 Klebsiella ozenae and 1 Serratia liquefaciens. Overall, 17 of 19 infections (89%) showed a satisfactory clinical response to trial therapy (15 cures and 2 improvements). Microbiological eradication was observed in 17 out of 20 isolated pathogens. Emergence of resistance to ciprofloxacin occurred in 1 coagulase-negative Staphylococcus and was associated with clinical failure. No side effects were observed. We conclude that intravenous ciprofloxacin may represent efficacious and safe therapy of severe infections; however close microbiological monitoring seems to be necessary to evaluate the emergence of resistance during quinolone therapy.     

Pancreatic cystadenocarcinoma and pregnancy: a case report

We report a case of cystadenocarcinoma occurring in a pregnant woman. After child birth, a subtotal pancreatectomy was performed, without rupture of the cyst. The patient is asymptomatic, 24 months after surgery. The presentation of cystadenocarcinoma in pregnancy has been reported in another single case. The possibility of hormonal dependence is discussed.     

Can colorectal cancer mass-screening organization be evidence-based? Lessons from failures: The experimental and pilot phases of the Lazio program

Background  

Screening programmes should be organized to translate theoretical efficacy into effectiveness. An evidence-based organizational model of colorectal cancer screening (CRCS) should assure feasibility and high compliance.