Performance of 18F-FDG PET/contrast-enhanced CT in the staging of squamous cell carcinoma of the oral cavity and oropharynx

The aim of this study was to assess the diagnostic value of integrated whole body positron emission tomography/contrast-enhanced CT (PET/CECT) as a one step examination in the initial staging of oral and oropharyngeal squamous cell carcinoma (OOSCC). Seventy three consecutive OOSCC patients who underwent PET/CECT for initial staging and tumour resection and neck dissection as primary treatment, were included. For each PET/CECT result, the contribution of fluorine-18 fluorodeoxyglucose (¹⁸F-FDG)-uptake and radiologic criteria was assessed. PET/CECT results were correlated to histological specimens obtained with tumour resection and neck dissection. For detecting the primary tumour PET/CECT showed a sensitivity of 96% and for detecting cervical metastases a sensitivity and specificity of 89% and 81%, respectively. In the clinically N0 subgroup (n = 37), PET/CECT showed a sensitivity and specificity of 64% and 81%, respectively. In five of six patients PET/CECT detected a second primary tumour. The results show that the use of diagnostic PET/CECT as a one step examination is a reliable alternative for PET/CT in combination with a separate diagnostic CT in patients with OOSC for initial staging. The need for treatment of the neck in the clinically negative neck should not be based on PET/CECT results only, due to the risk of missing a small metastasis.     

Comment on the use of self‐reporting instruments to assess patients with rheumatoid arthritis: The longitudinal association between the DAS28 and the VAS general health

Objective

Recently, the use of patient self‐reporting instruments instead of clinical, objective measurements to assess rheumatoid arthritis (RA) patients was proposed. This assumes a constant association between disease activity and the self‐reporting instruments. The objective was to explore the association (in time) between disease activity and patient perception of general health, disease activity, pain, and functional disability in patients with RA.

Methods

Data of 624 newly diagnosed RA patients who completed 3 years of followup were analyzed. Cross‐sectional linear regression models and longitudinal regression models were estimated, with a visual analog scale (VAS) measuring general health (VAS‐GH; 0 = best, 100 = worst) as a dependent variable and the Disease Activity Score (DAS28) without the VAS‐GH as an independent variable. Other dependent variables were VAS disease activity, pain, and the Health Assessment Questionnaire.

Results

The DAS28 and VAS‐GH were significantly associated in RA patients (P < 0.001). However, the explained variance was low (6.7%). From diagnosis to 3 years after the diagnosis, the intercept decreased given the same regression coefficient. The longitudinal regression model showed that the VAS‐GH improved during disease course independent of a change in DAS28. Analyses on the other outcome parameters showed similar results.

Conclusion

Patients' perception of health can be different with equal disease activity, depending on the moment in the disease course. Furthermore, our results indicate that self‐reported measures on functionality, disease activity, and general health cannot substitute for objective measures of disease activity in RA in longitudinal studies; subsequently, both need to be measured.

     

Activation of serotonin receptors promotes microglial injury-induced motility but attenuates phagocytic activity

Microglia, the brain immune cell, express several neurotransmitter receptors which modulate microglial functions. In this project we studied the impact of serotonin receptor activation on distinct microglial properties as serotonin deficiency not only has been linked to a number of psychiatric disease like depression and anxiety but may also permeate from the periphery through blood-brain barrier openings seen in neurodegenerative disease. First, we tested the impact of serotonin on the microglial response to an insult caused by a laser lesion in the cortex of acute slices from Cx3Cr1-GFP-/+ mice. In the presence of serotonin the microglial processes moved more rapidly towards the laser lesion which is considered to be a chemotactic response to ATP. Similarly, the chemotactic response of cultured microglia to ATP was also enhanced by serotonin. Quantification of phagocytic activity by determining the uptake of microspheres showed that the amoeboid microglia in slices from early postnatal animals or microglia in culture respond to serotonin application with a decreased phagocytic activity whereas we could not detect any significant change in ramified microglia in situ. The presence of microglial serotonin receptors was confirmed by patch-clamp experiments in culture and amoeboid microglia and by qPCR analysis of RNA isolated from primary cultured and acutely isolated adult microglia. These data suggest that microglia express functional serotonin receptors linked to distinct microglial properties.     

‘Diabetes is a gift from god’ a qualitative study coping with diabetes distress by Indonesian outpatients

Quality of Life Research - More than two-thirds of patients diagnosed with type 2 diabetes mellitus (T2DM) in Indonesia encounter medical-related problems connected to routine self-management of...     

Ageing is associated with a prolonged fever response in human endotoxemia

The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-alpha and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.     

Circulating adiponectin levels during human endotoxaemia

Adiponectin, an adipocytokine secreted by fat tissue, may prevent development of diabetes type II, as high adiponectin levels are linked with insulin sensitivity. In contrast, tumour necrosis factor (TNF)-alpha, which is also produced by fat tissue, leads to insulin resistance and furthermore inhibits adiponectin mRNA production and secretion of the protein. However, adiponectin also negatively regulates TNF-alpha levels. Therefore, we set out to test whether an infusion of endotoxin would influence circulating adiponectin levels in healthy human subjects. Twenty-three healthy human subjects were injected with endotoxin (2 ng/kg body weight); eight of these subjects were also injected with saline and served as controls. Plasma levels of adiponectin, TNF-alpha and interleukin-6 were measured at 0, 1.5, 2, 4, 8 and 24 h. TNF-alpha and interleukin-6 levels peaked at 1.5 h and 2 h, respectively. Control subjects injected with saline showed a decrease in adiponectin plasma levels with time (P < 0.05) presumably owing to the effect of fasting or physical inactivity. However, there was no change in adiponectin plasma levels in endotoxin injected subjects, thus the effect of fasting was opposed. In conclusion, circulating adiponectin levels are reduced during a resting and fasting state, an effect reversed by endotoxin injection.     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Amygdala Inhibitory Circuits Regulate Associative Fear Conditioning

Associative memory formation is essential for an animal’s survival by ensuring adaptive behavioral responses in an ever-changing environment. This is particularly important under conditions of immediate threats such as in fear learning. One of the key brain regions involved in associative fear learning is the amygdala. The basolateral amygdala is the main entry site for sensory information to the amygdala complex, and local plasticity in excitatory basolateral amygdala principal neurons is considered to be crucial for learning of conditioned fear responses. However, activity and plasticity of excitatory circuits are tightly controlled by local inhibitory interneurons in a spatially and temporally defined manner. In this review, we provide an updated view on how distinct interneuron subtypes in the basolateral amygdala contribute to the acquisition and extinction of conditioned fear memories.     

Discrete Choice Modeling for the Quantification of Health States: The Case of the EQ-5D

ObjectivesProbabilistic models have been developed to establish the relative merit of subjective phenomena by means of specific judgmental tasks involving discrete choices (DCs). The attractiveness of these DC models is that they are embedded in a strong theoretical measurement framework and are based on relatively simple judgmental tasks. The aim of our study was to determine whether the values derived from a DC experiment are comparable to those obtained using other valuation techniques, in particular the time trade-off (TTO).MethodsTwo hundred nine students completed several tasks in which we collected DC, rank, visual analog scale, and TTO responses. DC data were also collected in a general population sample (N = 444). The DC experiment was designed using a Bayesian approach, and involved 60 choices between two health states and a comparison of all health states to being dead. The DC data were analyzed using a conditional logit and a rank-ordered logit model, relying, respectively, on TTO values and the value for being dead to anchor the DC-derived values to the 0 to 1 quality-adjusted life-year (QALY) scale.ResultsAlthough modeled DC data broadly replicated the pattern found in TTO responses, the DC consistently produced higher values. The two methods for anchoring DC-derived values on the QALY scale produced similar results.ConclusionsOn the basis of the high level of comparability between DC-derived values and TTO values, future valuation studies based on a combination of these two techniques may be considered. The results further suggest that DC can potentially be used as a substitute for TTO.     

Visual analogue scales: scale recalibration by patients with dementia and their proxies

Background

Visual analogue scales (VAS) are often used to measure health-related quality of life (HRQoL). However, when such scales contain ambiguous anchors like “best imaginable health state,” they produce answers that are difficult to interpret, as such anchors are interpreted differently by respondents of different age. This phenomenon that people’s interpretation of subjective response scales changes in response to changing circumstances is known as scale recalibration. The current study attempts to investigate whether scale recalibration in a patient sample with cognitive limitations and proxies differs from the general population.

Methods

The participants in the current study were 151 pairs of community-dwelling patients with dementia and their proxies. They were administered three VASs with different upper anchors; (A) “best imaginable health state,” (B) “best imaginable health state for someone your age,” and (C) “best imaginable health state for a 25-year-old.” From literature, we inferred a conceptual model for the general population that predicts the ordinal relationship of the VASs to be B ≥ A ≥ C. This rank order is tested by repeated measure ANOVA’s in the aforementioned populations.

Results

VAS scores of patients with dementia were in line with the conceptual model. Proxy VAS scores for assessing patient HRQoL were not in line with the model: A > B > C. In addition, proxy VAS scores for assessing their own health were not in line with the model: A > B > C.

Conclusion

Patients with dementia use the VAS in a similar way to the general population. Proxies assessing either patients or themselves differ from the general population.