Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.     

Cigarette smoking and risk of non-Hodgkin's lymphoma--a population-based case-control study.

BACKGROUND: Epidemiologic evidence of an association between tobacco smoking and non-Hodgkin's lymphoma has been conflicting. This may reflect that non-Hodgkin's lymphoma comprises several distinct disease entities with different etiologies, as some studies have indicated an association between smoking and follicular lymphoma. OBJECTIVE: To investigate the association between cigarette smoking and non-Hodgkin's lymphoma risk, overall and by subtype. METHODS: As part of a nationwide Danish-Swedish population-based case-control study, we interviewed 3,055 incident non-Hodgkin's lymphoma patients and 3,187 population controls. All lymphomas were uniformly classified according to the WHO classification. We used unconditional logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for the association between cigarette smoking and risk of non-Hodgkin's lymphoma. RESULTS: Cigarette smoking was not associated with the risk of non-Hodgkin's lymphoma overall (OR, 0.97; 95% CI, 0.87-1.08) nor with the major subgroups such as diffuse large B-cell lymphoma (OR, 0.94; 95% CI, 0.79-1.10), chronic lymphocytic leukemia (OR, 0.86; 95% CI, 0.72-1.02), or follicular lymphoma (OR, 1.03; 95% CI, 0.85-1.24). Female smokers were at a marginally increased risk of follicular lymphoma (OR, 1.41; 95% CI, 1.04-1.92). Men who had ever smoked had a significantly increased risk of T-cell lymphoma (OR, 1.67; 95% CI, 1.11-2.51). No dose-response association with cigarette smoking could be established for any lymphoma subgroup. CONCLUSION: We found little evidence of an association between cigarette smoking and non-Hodgkin's lymphoma risk overall. Although increased risks of follicular lymphoma in female smokers and of T-cell lymphoma in male smokers were suggested, no dose-response relationship was observed, leaving limited support for causality.     

Revision Hip Arthroplasty with A Modular Cementless Stem: Mid-Term Follow Up

Despite the increasing volume of revision total hip arthroplasty (THA) being performed in the United States, there are few studies reporting mid-term clinical and radiographic outcomes of modular fully porous-coated femoral stems. We retrospectively studied a consecutive series of patients who underwent revision THA with a modular extensively porous-coated femoral component at a single institution and by a single surgeon. The final study group included 54 hips (52 patients) followed for an average of 84 months. Ten-year survival rates with revision for any reason and revision for femoral loosening as endpoints were 94% and 100%, respectively. No complications regarding the modular junction were encountered. Of the 50 hips with adequate radiographs, all showed proximal ingrowth and 42 (84%) had both proximal and distal ingrowth. The modular, fully porous-coated femoral stem studied demonstrated excellent survivorship and bone ingrowth at mid-term follow up.     

Being in transit and in transition The experience of time at the place,when living with severe incurable disease ‐ a phenomenological study

The aim of this study is to describe the experience of time as it presents itself at the place being situated when living with severe incurable disease and receiving palliative care. The empirical data consist of 26 open‐ended interviews with 23 patients receiving palliative care at home, at a palliative day care, in a palliative bed unit in hospital or in a nursing home in Norway. A common meaning of a shifting space for living emerged from the analysis and was revealed through three different aspects: (i) Transition from a predictable to an unpredictable time: To live with severe incurable disease marks a transition to a changed life involving an ongoing weakened and altered body with bothersome symptoms making experience of time different and unpredictable. (ii) Transition between a safe and unsafe time: When time is unpredictable, feeling safe is revealed as essential to how time is experienced at the place being situated. (iii) To be in transition from a homely to a homeless existence: In a time of increased bodily weakness, unpredictable ailments and displacements, the sense of belonging to the place is revealed as significant to the experience of time. Not knowing where to be in a time of change is like an existential cry of distress where the foothold in existence is lost. The findings are discussed and interpreted as an embodied experience originating from the passage of time continually affecting life sometimes so fundamentally that it marks a transition to a changed space of life that is reflected in the experience of time.     

MZB1 is a GRP94 cochaperone that enables proper immunoglobulin heavy chain biosynthesis upon ER stress

MZB1 (pERp1) is a B-cell-specific and endoplasmic reticulum (ER)-localized protein implicated in antibody secretion and integrin-mediated cell adhesion. Here, we examine the role of MZB1 in vivo by conditional gene inactivation in the mouse germline and at different stages of B lymphopoiesis. Deletion of MZB1 impairs humoral immune responses and antibody secretion in plasma cells that naturally undergo ER stress. In addition, we found that experimental induction of ER stress by tunicamycin injections in mice results in a block of pro-B-cell to pre-B-cell differentiation specifically in Mzb1^−/− mice. A similar developmental block was observed in Mzb1^fl/flmb1^Cre mice, whereby a Cre recombinase-induced genotoxic stress unmasks a role for MZB1 in the surface expression of immunoglobulin µ heavy chains (µHCs). MZB1 associates directly with the substrate-specific chaperone GRP94 (also called HSP90B1 or gp96) in an ATP-sensitive manner and is required for the interaction of GRP94 with µHCs upon ER stress. Thus, MZB1 seems to act as a substrate-specific cochaperone of GRP94 that enables proper biosynthesis of µHCs under conditions of ER stress.     

Motility of Campylobacter concisus isolated from saliva,feces, and gut mucosal biopsies

Campylobacter concisus is an emerging pathogen associated with gastrointestinal disorders such as gastroenteritis and inflammatory bowel diseases (IBD), but the species is also found in healthy subjects. The heterogeneous genome of C. concisus increases the likelihood of varying virulence between strains. Flagella motility is a crucial virulence factor for the well‐recognized Campylobacter jejuni; therefore, this study aimed to analyze the motility of C. concisus isolated from saliva, gut biopsies, and feces of patients with IBD, gastroenteritis, and healthy subjects. The motility zones of 63 isolates from 52 patients were measured after microaerobic growth in soft‐agar plates for 72 hours. The motility of C. concisus was significantly lower than that of Campylobacter jejuni and Campylobacter fetus subsp. fetus. The motility of C. concisus varied between isolates (4–22 mm), but there was no statistical significant difference between isolates from IBD patients and healthy subjects (p = 0.14). A tendency of a larger motility zones was observed for IBD gut mucosa isolates, although it did not reach statistical significance (p = 0.13), and no difference was found between oral or fecal isolates between groups. In conclusion, the varying motility of C. concisus could not be related to disease outcome or colonization sites.