Herpesvirus infections in children with acute lymphatic leukemia

33 children with acute lymphatic leukemia and 33 healthy controls were longitudinally studied for herpesvirus infections. Active herpes simplex-virus, varicella-zoster virus and cytomegalovirus (CMV) infections were more frequent in patients than in controls. CMV and Epstein-Barr virus infections were often inapparent or associated with infections of the upper respiratory tract. Analysis of serological datas revealed a coincidence of active CVM infection and lethal course of the leukemia. This may be a result of the immunodeficiency in leukemia patients caused by disease and therapy. An additional influence of the immunosuppressive effect of active CMV infections on the course of the disease is discussed.     

Heat Flow from Rechargeable Neuromodulation Systems into Surrounding Media

A synergistic investigation involving both experiment and numerical simulation was performed in vitro to determine the heat flow from rechargeable neuromodulation systems into surrounding media. Each system consists of an implant and an external recharging antenna, and the heat flows of each of these components were determined separately. Three systems, each produced by a different medical device firm, were evaluated. The evaluated products included those from Medtronic Inc. (MDT), ANS (a St. Jude Company), and the Boston Scientific Company (BSC, formerly Advanced Bionics). To ensure statistical significance, three nominally identical samples of each of the three systems were included in the study. Furthermore, for each sample of each system, replicate evaluations were performed for both the implant and the antenna. It was found that for both components of MDT, substantially lower rates of heat flow were produced compared with those for ANS and BSC. With regard to the latter systems, the higher rates of heat flow were not consistently ordered for the implant and for the antenna. In general, replicate data runs for each system and each component were in satisfactory agreement. The different samples of the MDT system showed only minor deviations with regard to heat flow. The deviations among the different samples of both ANS and BSC were larger than those evidenced for MDT.     

Effects of implementation of psychiatric guidelines on provider performance and patient outcome: systematic review

OBJECTIVE: To identify evidence from comparative studies on the effects of psychiatric guideline implementation on provider performance and patient outcome. Effects of different implementation strategies were reviewed. METHOD: Articles published between 1966 and March 2006 were searched through electronic databases and hand search. A systematic review of comparative studies of structured implementation of specific psychiatric guidelines was performed. Rates of guideline adherence, provider performance data, illness detection and diagnostic accuracy rates were extracted in addition to patient relevant outcome data. RESULTS: Eighteen studies (nine randomized-controlled trials, six non-randomized-controlled studies and three quasiexperimental before-and-after studies) were identified. Effects on provider performance or patient outcome were moderate and temporary in most cases. Studies with positive outcomes used complex multifaceted interventions or specific psychological methods to implement guidelines. CONCLUSION: There is insufficient high-quality evidence to draw firm conclusions on the effects of implementation of specific psychiatric guidelines.     

Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study

Background and Aims

Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies.

Methods

We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI).

Results

Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy.

Conclusions

ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.     

Contrast media: future aspects

In spite of the dramatic development in CT, there was no major breakthrough in the iodinated contrast media development. New agents based on hybrid between MRI and CT compounds may be a new innovative alternative. This new approach may also open new indications such as radiotherapy.     

Magnetic resonance imaging of atherosclerosis by targeting extracellular matrix deposition with Gadofluorine M

As previously reported, Gadofluorine M‐enhanced magnetic resonance imaging clearly demarcates atherosclerotic plaques from the normal vessel wall. To date, the underlying mechanism has remained unknown. Gadofluorine M is a gadolinium‐containing macrocyclic contrast agent containing hydrophilic and hydrophobic moieties. To elucidate the mechanism of accumulation, fluorescently labeled and radioactively labeled derivates of Gadofluorine M were used to determine affinity and specificity of Gadofluorine M binding to blood serum and plaque components in vitro and for the distribution within the plaque of WHHL rabbits in vivo. Gadofluorine M binds to serum albumin, leading to a breakdown of micelles after intravenous injection. The affinity of Gadofluorine M to serum albumin is k_D = 2 µmol/l. Gadofluorine then penetrates the atherosclerotic plaque while bound to albumin and then accumulates within the extracellular, fibrous parts of the plaque by binding to collagens, proteoglycans and tenascin, having the same affinity to these plaque constituents as to albumin. In contrast, weak binding was determined to LDL (k_D = 2 mmol/l) and even no binding to hyaluronic acid. The driving force of binding and accumulation is the hydrophobic moiety of the molecules interacting with hydrophobic plaque materials. Thus, Gadofluorine M accumulates within the fibrous plaque or in the fibrous cap of a plaque containing high amounts of extracellular matrix components, but not in the lipid‐rich areas. In combination with high‐resolution MRI, Gadofluorine M might enable the detection of thin‐cap fibroatheromas, also named the vulnerable plaque. Copyright © 2007 John Wiley & Sons, Ltd.