Responsiveness of the generic EQ-5D summary measure compared to the disease-specific EORTC QLQ C-30

Introduction: We investigated whether the sensitivity of the generic health-related quality of life (HRQoL) EQ-5D summary measure (or index) to detect changes over time in a clinical setting is comparable with that of a disease-specific HRQoL questionnaire. Methods: Patients with liver metastases (n = 75) filled out the five domains of the EQ-5D self-classifier, the EQ VAS, and the EORTC QLQ C-30 (a disease-specific (cancer) HRQoL questionnaire). The HRQoL instruments were completed before intervention, and 1/2 month and 3 and 6 months after intervention. Three analyses were performed. First, the EQ-5D index (based on self-classification) was compared to the EQ VAS. Second, the EQ-5D domains were compared to corresponding EORTC QLQ C-30 scales. Third, EQ-5D index and EQ VAS were compared with the EORTC QLQ C-30 global health-status scale. Effect size was chosen as the metric of responsiveness. Results: The EQ-5D index was slightly less responsive than the EQ VAS. Overall, the responsiveness of the EQ-5D index and EQ VAS was equal to the EORTC QLQ C-30 global health-status scale. Conclusion: Despite its generic principle and the apparent crudeness of its framework, the responsiveness of the EQ-5D proved to be comparable to that of a disease-specific HRQoL questionnaire in this specific clinical setting.     

Perioperative Outcomes Following Surgical Resection of Renal Cell Carcinoma with Inferior Vena Cava Thrombus Extending Above the Hepatic Veins: A Contemporary Multicenter Experience

Background

Surgery for renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus above the hepatic veins is technically complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with poor outcomes.

Objective

To determine the preoperative predictors of major complications and 90-d mortality after surgery in RCC patients who have IVC thrombus above the hepatic veins.

Design, setting, and participants

We reviewed medical records of all RCC patients who had IVC tumor thrombus above hepatic veins and had had surgery between January 2000 and December 2012 at the Mayo Clinic, M.D. Anderson Cancer Center, University of Texas Southwestern Medical Center, and the University of Wisconsin Hospital.

Outcome measurement and statistical analysis

Major complications recorded were defined as ≥3A according to the Clavien-Dindo system within 90 d of surgery. Univariate and multivariate analyses were used to evaluate associations of preoperative variables with risk of major complications or 90-d mortality.

Results and limitations

A total of 162 patients were identified for study (level 3, 4 in 69, 93 patients, respectively, according to the Neves classification). Cardiopulmonary bypass was used in 60 of 162 patients (37.5%), and 40 patients (24.7%) had preoperative angioembolization. Major complications were reported in 55 patients (34.0%), with the most common being respiratory, cardiac, and hematologic issues. After multivariate analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with increased risk of major complications. Mortality was reported in 17 patients (10.5%) within 90 d after surgery. After multivariate analysis, Eastern Cooperative Oncology Group (ECOG) performance status (PS) and low serum albumin were preoperative factors independently associated with increased risk of 90-d mortality.

Conclusions

Contemporary perioperative mortality and major complication rates for RCC patients who have upper-level thrombus are 10% and 34%, respectively. Patients who have ECOG PS >1 or low serum albumin have increased risk for perioperative mortality.     

Retrograde perfusion in isolated perfused mouse lungs—Feasibility and effects on cytokine levels and pulmonary oedema formation

Retrograde lung vascular perfusion can appear in high‐risk surgeries. The present report is the first to study long‐term retrograde perfusion of isolated perfused mouse lungs (IPLs) and to use the tyrosine kinase ephB4 and its ligand ephrinB2 as potential markers for acute lung injury. Mouse lungs were subjected to anterograde or retrograde perfusion with normal‐pressure ventilation (NV) or high‐pressure ventilation (=overventilation, OV) for 4 hours. Outcome parameters were cytokine, ephrinB2 and ephB4 levels in perfusate samples and bronchoalveolar lavage (BAL), and the wet‐to‐dry ratio. Anterograde perfusion was feasible for 4 hours, while lungs receiving retrograde perfusion presented considerable collapse rates. Retrograde perfusion resulted in an increased wet‐to‐dry ratio when combined with high‐pressure ventilation; other physiological parameters were not affected. Cytokine levels in BAL and perfusate, as well as levels of soluble ephB4 in BAL were increased in OV, while soluble ephrinB2 BAL levels were increased in retrograde perfusion. BAL levels of ephrinB2 and ephB4 were also determined in vivo, including mice ventilated for 7 hours with normal‐volume ventilation (NVV) or high‐volume ventilation (HVV) with increased levels of ephB4 in HVV BAL compared to NVV. Retrograde perfusion in IPL is limited as a routine method to investigate effects due to collapse for yet unclear reasons. If successful, retrograde perfusion has an influence on pulmonary oedema formation. In BAL, ephrinB2 seems to be up‐regulated by flow reversal, while ephB4 is a marker for acute lung injury.     

Frequency vs. intensity: Framing effects on patients' use of verbal rating scale anchors

Background

The present study examined the hypothesis that patients' ratings would be less congruent and stable if they were asked to rate imprecise terms on frequency and intensity that were embedded in a behavioral or perceptual framework. Based on data acquired from the patients' ratings the presented terms were analyzed concerning their interindividual congruency, intraindividual stability across time and distinguishability of adjacent terms. Afterward, the results were compared to the results regarding the same analysis of unframed terms from an earlier investigation [16].

Methods

In a longitudinal design, 44 patients (age M = 39.1, SD = 15.2, 68.2% female) with a depressive disorder filled out two established questionnaires (BDI or SCL-90) and questionnaires containing frequency and intensity terms framed in sentences concerning the subjective experience of sadness. Patients should rate the terms with regard to the percentage of time or intensity that is reflected by each term at two different measuring times within one week. Data analysis contained t-tests for paired samples and effect sizes d according to Cohen.

Results

The congruency of framed terms was influenced by an additional factor (vocabulary skills) in comparison to unframed terms. However, congruencies for both sets of terms were rather low. In contrast to unframed items, framed terms showed no intraindividual instability for frequency and intensity terms at all, but were influenced by all of the analyzed factors (age, gender, vocabulary skills, depression, and overall mental symptom burden). Patients could distinguish more adjacent framed terms than unframed terms.

Conclusions

The results give no clear suggestion if unframed or framed terms should be preferred as verbal anchors in self-report instruments. Unframed terms seem to have a slight advantage over framed terms as they are less influenced by the patient's background. However, patients are able to distinguish more adjacent terms if presented framed in a behavioral or perceptual context they are familiar with. Frequency terms showed a higher intraindividual stability of mental representations while both groups of terms exhibited low interindividual congruency. No more than four different verbal anchors could be used safely together in rating scales, as patients with a depressive disorder would not be able to reasonably differentiate more than these.     

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.     

Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer.

BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. RESULTS: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels. CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.     

Concurrent uveoretinitis and pineocytoma in a child suggests a causal relationship.

Uveoretinitis was observed in a 9-year-old girl 6 months prior to the clinical appearance of a pineal tumour. Surgical removal was not successful but biopsy revealed a parenchymal neoplasm with differentiated pinealocytes and absent mitotic activity. Some of the tumour cells contained S-antigen, rhodopsin, and serotonin. Systemic glucocorticoid therapy followed by radiation therapy caused considerable reduction in size of the tumour and a complete normalisation of all eye symptoms. This report demonstrates for the first time that a pineocytoma can occur together with uveoretinitis in humans. The latter resembles the experimentally induced autoimmune uveoretinitis described in animals. It is speculated that the retinitis might reflect an autoimmune response to S-antigen present in some tumour cells of the pineocytoma.