Secreted Wnt Antagonists During Eradication of Cytomegalovirus Infection in Solid Organ Transplant Recipients

We evaluated secreted wingless (Wnt) modulators during cytomegalovirus (CMV) infection in solid organ transplant recipients (SOTr). The major findings were: (i) Plasma levels of Dickkopf‐1 (DKK‐1) were significantly lower in patients with CMV DNAemia above lower level of quantification at baseline. (ii) Receiver operating characteristic analysis indicated that low DKK‐1 and increased secreted frizzled related protein‐3 levels were predictors of poor virological outcomes during follow‐up. Our findings demonstrate an imbalanced pattern of circulating secreted Wnt modulators in SOTr with poor virological outcomes following treatment for CMV disease, and may suggest a role for dysregulated Wnt signaling on viral pathogenesis during CMV infection.     

Kidney allograft subclinical rejection modulates systemic inflammation measured by C‐reactive protein at 1 year after transplantation

Kidney allograft inflammation is associated with proinflammatory modifications of peripheral blood mononuclear cells, suggesting that renal inflammation contributes to systemic inflammation. Thus, the aim of this study was to evaluate the relationship between subclinical inflammation in surveillance biopsies performed at 1 year and systemic inflammation assessed by C‐reactive protein (CRP) levels at the time of biopsy. We analyzed 544 surveillance biopsies performed at 1 year that were classified as normal (n = 368), borderline (n = 148), or subclinical rejection (SCR) (n = 28). CRP levels were divided into quartiles. Patients in 1st, 2nd, and 3rd quartile were classified as low CRP (n = 408) and patients in the 4th quartile as high CRP (n = 136). Univariate analysis showed that the proportion of patients with SCR was higher in the high CRP group (10.3% vs 3.4%, P = 0.0067). Multivariate analysis showed that independent predictors of high CRP were body mass index (odds ratio [OR] 1.072 and 95% confidence interval [CI] 1.027‐1.119), a positive urine culture at the day of the biopsy (OR 2.760 and 95% CI 1.205‐6.323), and the presence of SCR at 1‐year surveillance biopsy (OR 7.260 and 95% CI 3.530‐14.935). In summary, we describe that subclinical acute rejection constitutes an independent predictor of systemic inflammation as measured by CRP.     

Genetic and Environmental Variances of Bone Microarchitecture and Bone Remodeling Markers: A Twin Study

All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size – void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high‐resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold‐based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ～18%) for the distal tibial total, cortical, and medullary cross‐sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p < 0.001). For the corresponding distal radius traits, genetic factors accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross‐twin cross‐trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (r_MZ = 0.49) than DZ (r_DZ = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle‐aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than differences in their environment. © 2014 American Society for Bone and Mineral Research.     

Markers of endothelial and platelet activation are associated with high on-aspirin platelet reactivity in patients with stable coronary artery disease

Introduction

Aspirin inhibits the cyclooxygenase-1 (COX-1) mediated thromboxane A2 synthesis. Despite COX-1 inhibition, in patients with coronary artery disease (CAD), platelets can be activated through other mechanisms, like activation by thrombin.

Materials and Methods

At baseline in this cross-sectional substudy of the ASCET trial, 1001 stable CAD patients, all on single aspirin treatment, were classified by the PFA100® method, as having high on-aspirin residual platelet reactivity (RPR) or not. Markers of hypercoagulability, endothelial and platelet activation as related to RPR, were evaluated to explore the potential mechanisms behind high on-aspirin RPR.

Results

Altogether, 25.9% (n = 259) of the patients were found to have high on-aspirin RPR. S-thromboxane B₂ levels were very low and did not differ between patients having high on-aspirin RPR or not. Patients with high on-aspirin RPR had significantly higher levels of von Willebrand Factor (vWF) (124 vs 100%, p < 0.001, platelet count (236 vs 224 × 10⁹/l, p = 0.008), total TFPI (68.4 vs 65.5 ng/ml, p = 0.005) and ß-thromboglobulin (ß-TG) (33.3 vs 31.3 IU/ml, p = 0.041) compared to patients with low on-aspirin RPR. No significant differences between the groups were observed in levels of endogenous thrombin generation (ETP), pro-thrombin fragment 1+2 (F1+2), D-dimer, soluble TF (sTF) or P-selectin (all p > 0.05).

Conclusions

The high on-aspirin RPR as defined by PFA100® seems not to be due to increased thrombin activity as evaluated with ETP, sTF, F1+2 or D-dimer. The elevated levels of platelet count, ß-TG, TFPI and especially vWF might be explained by increased endothelial and platelet activation in these patients.     

Long‐term follow‐up of tailored behavioural treatment and exercise based physical therapy in persistent musculoskeletal pain: A randomized controlled trial in primary care

This study examined long‐term effects of a tailored behavioural treatment protocol (TBT), as compared with an exercise based physical therapy protocol (EBT). One‐hundred and twenty‐two patients who, due to persistent musculoskeletal pain, consulted physical therapists in primary care were originally randomized to either of the two conditions. Follow‐up assessments two‐year post‐treatment were completed by 65 participants. According to per‐protocol analyses, short‐term effects were maintained in both groups for the primary outcome, pain‐related disability. The TT‐group reported lower disability levels compared with the EBT‐group. Intention‐to‐treat analyses (ITT) conveyed similar results. Secondary outcomes of pain intensity, pain control, and functional self‐efficacy were maintained over the 2‐year post‐treatment, but previous group differences were levelled out according to the most conservative method of ITT. Fear of movement/(re)injury increased in the EBT‐group, and EBT participants reported higher fear of movement/(re)injury two years post‐treatment compared to TT. The study supports tailoring of treatments in concordance with patients’ needs and preferences of activity goals and functional behavioural analyses including predictors of pain‐related disability, for successful immediate outcomes and their maintenance in the long run. Exercise‐based treatments resulted in somewhat smaller immediate treatment effects but had similar maintenance of effects over the 2‐year follow‐up period.     

Nuclear imaging of molecular processes in cancer

Molecular imaging using radionuclides has brought about the possibility to image a wide range of molecular processes using radiotracers injected into the body at very low concentrations that should not perturb the processes being studied. Examples include specific peptide receptor expression, angiogenesis, multi drug resistance, hypoxia, glucose metabolism, and many others. This article presents an overview, aimed at the non-specialist in imaging, of the radionuclide imaging technologies positron emission tomography and single photon radionuclide imaging, and some of the molecules labeled with gamma- and positron-emitting radioisotopes that have been, or are being, developed for research and clinical applications in cancer.     

Diagnostic considerations of tongue-base malignancies

Summary Forty-two patients with malignancies localized to the base of the tongue were treated at Sahlgrenska Hospital between 1971 and 1980. These patients were re-analyzed with respect to symptomatology and clinical outcome. Pain in the mouth, throat, and ears as well as swallowing difficulties were the most frequent overt symptoms of disease. In general, patients experienced symptoms for at least 3 months before a positive tumor diagnosis was made. In all, 75% of the patients were found to have large tumors which extended beyond the base of the tongue. Most of the patients were treated with irradiation. The overall 3-year survival rate was 28%, while individual patient survival was related to the size of the primary tumor and to the occurrence of lymph node metastases. Careful attention to symptomatology may reduce delays in establishing an accurate diagnosis and consequently improve the prognosis for patients with these cancers.