The clinical significance of incidental intra-abdominal findings on positron emission tomography performed to investigate pulmonary nodules

<p>Abstract</p> <p>Background</p> <p>Lung cancer is a common cause of cancer-related death. Staging typically includes positron emission tomography (PET) scanning, in which¹⁸F-fluoro-2-dexoy-D-glucose (FDG) is taken up by cells proportional to metabolic activity, thus aiding in differentiating benign and malignant pulmonary nodules. Uptake of FDG can also occur in the abdomen. The clinical significance of incidental intraabdominal FDG uptake in the setting of pulmonary nodules is not well established. Our objective was to report on the clinical significance of incidental intra-abdominal FDG activity in the setting of lung cancer.</p> <p>Methods</p> <p>Fifteen hundred FDG-PET reports for studies performed for lung cancer were retrospectively reviewed for the presence of incidental FDG-positive intraabdominal findings. Patient charts with positive findings were then reviewed and information extracted.</p> <p>Results</p> <p>Twenty-five patients (25/1500) demonstrated incidental intraabdominal FDG uptake thought to be significant (1.7%) with a mean patient age of 71 years. Colonic uptake was most common (n = 17) with 9 (52%) being investigated further. Of these 9 cases, a diagnosis of malignancy was made in 3 patients, pre-malignant adenomas in 2 patients, a benign lipoma in 1 patient and no abnormal findings in the remaining patients. 8 patients were not investigated further (3 diagnosed with metastatic lung cancer and 2 were of advanced age) secondary to poor prognosis.</p> <p>Conclusion</p> <p>Incidental abdominal findings in the colon on FDG-PET scan for work-up of pulmonary nodules need to be further investigated by colonoscopy.</p

Longitudinal peak strain detects a smaller risk area than visual assessment of wall motion in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis (peak strain, displacement, mitral annular movement (MAM)) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality ≥50%.</p> <p>Methods</p> <p>Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality.</p> <p>Results</p> <p>On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences (p ≤ 0.001, p ≤ 0.001, p ≤ 0.001 and p = 0.03) between the two study visits, but MAM did not (p = 0.17). On all levels (global, regional and segmental) and both pre- and post PCI, WMSI showed a higher correlation with scar transmurality compared to strain. We found that both strain and WMSI predicted the development of scar transmurality ≥50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis.</p> <p>Conclusions</p> <p>In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality ≥50% at follow-up.</p

An Empirical Explanation of the Speed-Distance Effect

Understanding motion perception continues to be the subject of much debate, a central challenge being to account for why the speeds and directions seen accord with neither the physical movements of objects nor their projected movements on the retina. Here we investigate the varied perceptions of speed that occur when stimuli moving across the retina traverse different projected distances (the speed-distance effect). By analyzing a database of moving objects projected onto an image plane we show that this phenomenology can be quantitatively accounted for by the frequency of occurrence of image speeds generated by perspective transformation. These results indicate that speed-distance effects are determined empirically from accumulated past experience with the relationship between image speeds and moving objects

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Enhancing treatment decision-making: pilot study of a treatment decision aid in stage IV non-small cell lung cancer

We developed a decision aid (DA) for patients with metastatic non-small cell lung cancer (NSCLC), to better inform patients of their prognosis and treatment options, and facilitate involvement in decision-making. In a pilot study, 20 patients with metastatic NSCLC attending outpatient clinics at a major cancer centre, who had already made a treatment decision, reviewed acceptability of the DA. The median age of the patients was 61 years (range 37–77 years), 35% were male, 20% had a university education, and most (75%) had English as a first language. Most had received chemotherapy, with 65% currently on treatment. Patients were not anxious at baseline and had clear understanding of the goals and toxicity of chemotherapy in advanced NSCLC. After reviewing the DA, patients' anxiety decreased slightly (P=0.04) and knowledge scores improved by 25% (P<0.001). Most improvements in understanding were of prognosis with and without chemotherapy, although patients still believed advanced NSCLC to be curable. Patients rated the DA highly with respect to information clarity, usefulness and were positive about its use in practice, although 40% found the prognostic information slightly upsetting. The DA for advanced NSCLC is feasible, acceptable to patients and improves understanding of advanced NSCLC without increasing patient anxiety

The Neuronal EGF-Related Gene Nell2 Interacts with Macf1 and Supports Survival of Retinal Ganglion Cells after Optic Nerve Injury

Nell2 is a neuron-specific protein containing six epidermal growth factor-like domains. We have identified Nell2 as a retinal ganglion cell (RGC)-expressed gene by comparing mRNA profiles of control and RGC-deficient rat retinas. The aim of this study was to analyze Nell2 expression in wild-type and optic nerve axotomized retinas and evaluate its potential role in RGCs. Nell2-positive in situ and immunohistochemical signals were localized to irregularly shaped cells in the ganglion cell layer (GCL) and colocalized with retrogradely-labeled RGCs. No Nell2-positive cells were detected in 2 weeks optic nerve transected (ONT) retinas characterized with approximately 90% RGC loss. RT-PCR analysis showed a dramatic decrease in the Nell2 mRNA level after ONT compared to the controls. Immunoblot analysis of the Nell2 expression in the retina revealed the presence of two proteins with approximate MW of 140 and 90 kDa representing glycosylated and non-glycosylated Nell2, respectively. Both products were almost undetectable in retinal protein extracts two weeks after ONT. Proteome analysis of Nell2-interacting proteins carried out with MALDI-TOF MS (MS) identified microtubule-actin crosslinking factor 1 (Macf1), known to be critical in CNS development. Strong Macf1 expression was observed in the inner plexiform layer and GCL where it was colocalizied with Thy-1 staining. Since Nell2 has been reported to increase neuronal survival of the hippocampus and cerebral cortex, we evaluated the effect of Nell2 overexpression on RGC survival. RGCs in the nasal retina were consistently more efficiently transfected than in other areas (49% vs. 13%; n = 5, p<0.05). In non-transfected or pEGFP-transfected ONT retinas, the loss of RGCs was approximately 90% compared to the untreated control. In the nasal region, Nell2 transfection led to the preservation of approximately 58% more cells damaged by axotomy compared to non-transfected (n = 5, p<0.01) or pEGFP-transfected controls (n = 5, p<0.01)

Palliative chemotherapy or best supportive care? A prospective study explaining patients' treatment preference and choice

Item does not contain fulltextIn palliative cancer treatment, the choice between palliative chemotherapy and best supportive care may be difficult. In the decision-making process, giving information as well as patients' values and preferences become important issues. Patients, however, may have a treatment preference before they even meet their medical oncologist. An insight into the patient's decision-making process can support clinicians having to inform their patients. Patients (n=207) with metastatic cancer, aged 18 years or older, able to speak Dutch, for whom palliative chemotherapy was a treatment option, were eligible for the study. We assessed the following before they consulted their medical oncologist: (1) socio-demographic characteristics, (2) disease-related variables, (3) quality-of-life indices, (4) attitudes and (5) preferences for treatment, information and participation in decision-making. The actual treatment decision, assessed after it had been made, was the main study outcome. Of 207 eligible patients, 140 patients (68%) participated in the study. At baseline, 68% preferred to undergo chemotherapy rather than wait watchfully. Eventually, 78% chose chemotherapy. Treatment preference (odds ratio (OR)=10.3, confidence interval (CI) 2.8-38.0) and a deferring style of decision-making (OR=4.9, CI 1.4-17.2) best predicted the actual treatment choice. Treatment preference (total explained variance=38.2%) was predicted, in turn, by patients' striving for length of life (29.5%), less striving for quality of life (6.1%) and experienced control over the cause of disease (2.6%). Patients' actual treatment choice was most strongly predicted by their preconsultation treatment preference. Since treatment preference is positively explained by striving for length of life, and negatively by striving for quality of life, it is questionable whether the purpose of palliative treatment is made clear. This, paradoxically, emphasises the need for further attention to the process of information giving and shared decision-making

Neuropeptidomic Components Generated by Proteomic Functions in Secretory Vesicles for Cell–Cell Communication

Diverse neuropeptides participate in cell–cell communication to coordinate neuronal and endocrine regulation of physiological processes in health and disease. Neuropeptides are short peptides ranging in length from ~3 to 40 amino acid residues that are involved in biological functions of pain, stress, obesity, hypertension, mental disorders, cancer, and numerous health conditions. The unique neuropeptide sequences define their specific biological actions. Significantly, this review article discusses how the neuropeptide field is at the crest of expanding knowledge gained from mass-spectrometry-based neuropeptidomic studies, combined with proteomic analyses for understanding the biosynthesis of neuropeptidomes. The ongoing expansion in neuropeptide diversity lies in the unbiased and global mass-spectrometry-based approaches for identification and quantitation of peptides. Current mass spectrometry technology allows definition of neuropeptide amino acid sequence structures, profiling of multiple neuropeptides in normal and disease conditions, and quantitative peptide measures in biomarker applications to monitor therapeutic drug efficacies. Complementary proteomic studies of neuropeptide secretory vesicles provide valuable insight into the protein processes utilized for neuropeptide production, storage, and secretion. Furthermore, ongoing research in developing new computational tools will facilitate advancements in mass-spectrometry-based identification of small peptides. Knowledge of the entire repertoire of neuropeptides that regulate physiological systems will provide novel insight into regulatory mechanisms in health, disease, and therapeutics

Synthetic Double-Stranded RNAs Are Adjuvants for the Induction of T Helper 1 and Humoral Immune Responses to Human Papillomavirus in Rhesus Macaques

Toll-like receptor (TLR) ligands are being considered as adjuvants for the induction of antigen-specific immune responses, as in the design of vaccines. Polyriboinosinic-polyribocytoidylic acid (poly I:C), a synthetic double-stranded RNA (dsRNA), is recognized by TLR3 and other intracellular receptors. Poly ICLC is a poly I:C analogue, which has been stabilized against the serum nucleases that are present in the plasma of primates. Poly I:C12U, another analogue, is less toxic but also less stable in vivo than poly I:C, and TLR3 is essential for its recognition. To study the effects of these compounds on the induction of protein-specific immune responses in an animal model relevant to humans, rhesus macaques were immunized subcutaneously (s.c.) with keyhole limpet hemocyanin (KLH) or human papillomavirus (HPV)16 capsomeres with or without dsRNA or a control adjuvant, the TLR9 ligand CpG-C. All dsRNA compounds served as adjuvants for KLH-specific cellular immune responses, with the highest proliferative responses being observed with 2 mg/animal poly ICLC (p = 0.002) or 6 mg/animal poly I:C12U (p = 0.001) when compared with immunization with KLH alone. Notably, poly ICLC—but not CpG-C given at the same dose—also helped to induce HPV16-specific Th1 immune responses while both adjuvants supported the induction of strong anti-HPV16 L1 antibody responses as determined by ELISA and neutralization assay. In contrast, control animals injected with HPV16 capsomeres alone did not develop substantial HPV16-specific immune responses. Injection of dsRNA led to increased numbers of cells producing the T cell–activating chemokines CXCL9 and CXCL10 as detected by in situ hybridization in draining lymph nodes 18 hours after injections, and to increased serum levels of CXCL10 (p = 0.01). This was paralleled by the reduced production of the homeostatic T cell–attracting chemokine CCL21. Thus, synthetic dsRNAs induce an innate chemokine response and act as adjuvants for virus-specific Th1 and humoral immune responses in nonhuman primates