Survival Prediction of Patients Who Were Terminally Ill Using the EORTC QLQ-C15-PAL Scores and Laboratory Test Values.

Background: Prognostics for patients with cancer is especially important for the supportive care of those who are terminally ill. We previously found that symptom scores as patient-reported outcomes (PROs)-such as dyspnea and fatigue scores-some biochemical parameters, the palliative performance scale (PPS) scores, and symptom clusters were useful prognostic factors; however, the predictability of a prognosis based on these factors remains unclear. Objective: To identify appropriate three-week survival predictive factor(s), in terms of performance, in patients who were terminally ill. Design: We collected symptom scores as PROs using the Japanese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL). Setting/Subjects: We used data from terminally ill patients with cancer who were hospitalized at the palliative care unit of the Higashisumiyoshi-Morimoto Hospital (Osaka, Japan) from June 2018 to December 2019 (n = 130), as well as additional data obtained from the same clinical study from January to March 2020 (n = 31). Measurements: To evaluate predictive performance, indices such as sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated. Results: We found that the presence of a symptom cluster showed high sensitivity but low specificity and that a higher PPS value (>30) showed high specificity but low sensitivity, suggesting that these factors could provide relevant information for survival prognosis (less than or equal to three weeks). Conclusion: Symptom clusters obtained from patients is important for effective supportive care of those who are terminally ill.

Symptom clusters and their influence on prognosis using EORTC QLQ-C15-PAL scores in terminally ill patients with cancer.

PURPOSE: The aims of the present study were to investigate the symptom clusters in terminally ill patients with cancer using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL), and to examine whether these symptom clusters influenced prognosis. METHODS: We analyzed data from 130 cancer patients hospitalized in the palliative care unit from June 2018 to December 2019 in an observational study. Principal component analysis was used to detect symptom clusters using the scored date of 14 items in the QLQ-C15-PAL, except for overall QOL, at the time of hospitalization. The influence of the existence of these symptom clusters and Palliative Performance Scale (PPS) on survival was analyzed by Cox proportional hazards regression analysis, and survival curves were compared between the groups with or without existing corresponding symptom clusters using the log-rank test. RESULTS: The following symptom clusters were identified: cluster 1 (pain, insomnia, emotional functioning), cluster 2 (dyspnea, appetite loss, fatigue, and nausea), and cluster 3 (physical functioning). Cronbach's alpha values for the symptom clusters ranged from 0.72 to 0.82. An increased risk of death was significantly associated with the existence of cluster 2 and poor PPS (log-rank test, p = 0.016 and p < 0.001, respectively). CONCLUSION: In terminally ill patients with cancer, three symptom clusters were detected based on QLQ-C15-PAL scores. Poor PPS and the presence of symptom cluster that includes dyspnea, appetite loss, fatigue, and nausea indicated poor prognosis.

The role of EORTC QLQ-C15-PAL scores and inflammatory biomarkers in predicting survival in terminally ill patients with cancer.

BACKGROUND: The clinical use of patient-reported outcomes as compared to inflammatory biomarkers for predicting cancer survival remains a challenge in palliative care settings. We evaluated the role of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative scores (EORTC QLQ-C15-PAL) and the inflammatory biomarkers C-reactive protein (CRP), albumin (Alb), and neutrophil-lymphocyte ratio (NLR) for survival prediction in patients with advanced cancer. METHODS: This was an observational study in terminally ill patients with cancer hospitalized in a palliative care unit between June 2018 and December 2019. Patients' data collected at the time of hospitalization were analyzed. Cox regression was performed to examine significant factors influencing survival. A receiver operating characteristic (ROC) analysis was performed to estimate cut-off values for predicting survival within 3 weeks, and a log-rank test was performed to compare survival curves between groups divided by the cut-off values. RESULTS: Totally, 130 patients participated in the study. Cox regression suggested that the QLQ-C15-PAL dyspnea and fatigue scores and levels of CRP, Alb, and NLR were significantly associated with survival time, and cut-off values were 66.67, 66.67, 3.0 mg/dL, 2.5 g/dL, and 8.2, respectively. The areas under ROC curves of these variables were 0.6-0.7. There were statistically significant differences in the survival curves between groups categorized using each of these cut-off values (p < .05 for all cases). CONCLUSION: Our findings suggest that the assessment of not only objective indicators for the systemic inflammatory response but also patient-reported outcomes using EORTC QLQ-C15-PAL is beneficial for the prediction of short-term survival in terminally ill patients with cancer.

Comparison of Patient Self-Reported Quality of Life and Health Care Professional-Assessed Symptoms in Terminally ill Patients With Cancer.

BACKGROUND: Few studies evaluated whether health care professionals accurately assess several symptoms for patients with cancer in palliative care units. We determined the agreement level for several symptoms related to quality of life (QOL) between patient-reported QOL assessment and health care professional-assessed symptoms based on the Support Team Assessment Schedule (STAS). METHOD: An observational study was performed with terminally ill patients with cancer hospitalized in the palliative care unit between June 2018 and December 2019. Patients and health care professionals independently assessed 7 symptoms at the time of hospitalization and after 1 week. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C15-PAL). In examining the proportions of exact agreement, "exact agreement" referred to the pairs of the scores (QLQ-C15-PAL vs STAS) being (1 vs 0), (2 vs 1), (3 vs 2 or 3), or (4 vs 4). The relationships of physical functioning between QLQ-C15-PAL and Palliative Performance Scale (PPS) were examined. RESULTS: Of 130 patients, approximately 60% had PPS scores from 40 to 60. The highest mean score on QLQ-C15-PAL was for fatigue (63.8). The exact agreement on symptoms between patients and health care professionals ranged from 15.4% (fatigue) to 57.7% (nausea and vomiting). The mean of the transformed QLQ-C15-PAL and proportions of exact agreement were negatively correlated (R 2 = 0.949, P < .05). The physical function scores in QLQ-C15-PAL for each PPS group showed no differences. CONCLUSION: We expect patient-reported outcomes including QLQ-C15-PAL to be added to health care professionals' assessment of serious symptoms such as fatigue in terminally ill patients with cancer.

[Differences in Measured Values among Homogenous Assay Reagents of LDL-C in LP-X Positive Serum Samples].

The LDL-C level measures with homogeneous (direct) assays in almost of clinical laboratories. Several reports however showed differences in measured values among the assay reagents. We investigated the differences in LDL-C values among direct assays and Friedewald formula (F-f) in 58 LP-X positive serum samples from jaundice patients by comparing LDL-C values measured by anion-exchange chromatography (AEX-HPLC), largely comparable to ultracentrifugation method. Changes in LDL-C values during the treatment of 8 patients were also investigated. Direct assay reagents from Sekisui Medical (S-r), Denka-Seiken (D-r), Wako Chemical (W-r), and Kyowa Medics (K-r) were used for comparison. F-f, S-r, and D-r correlated with AEX-HPLC with r values < 0.6 while W-r and K-r correlated with AEX-HPLC with r-vales > 0.6. Two samples in which F-f values provided 500 mg/dL plus bias to AEX-HPLC (LDL-C value of 220 mg/dL) demonstrated increased levels of IDL-C before treatment. LDL-C values (S-r and D-r) of the 2 samples were relatively high and near to F-f data while LDL-C values (W-r and K-r) were relatively low and close to AEX-HPLC data. The jaundice treatment decreased LDL-C values (S-r and D-r) and converged to 220 mg/dL, indicating that S-r and D-r might react markedly to IDL. These changes were consistent with decreases in serum free cholesterol and phospholipid in support of LP-X. By contrast, W-r and K-r data showed upward tendency and also converged to 220 mg/dL. These results suggest that LDL-C direct assay reagents would be classified into 2 groups with respect to the reagent reactivity to LP-X.

[Temporary use of centrifugal pump for pump thrombosis in patients with paracorporeal ventricular assist device].

Nipro paracorporeal ventricular assist device( VAD) is often associated with pump thrombosis which causes severe complications such as brain infarction, often requiring pump change. However, Nipro VAD pump is an expensive device and it is difficult to change pumps frequently at a short interval. We have temporarily used Rotaflow centrifugal pump for recurrent pump thrombosis in patients with Nipro VADs. From January 2012 through December 2013, 19 patients underwent Nipro VADs implantation at our institution, and 9 of them underwent pump change from Nipro pumps to Rotaflow centrifugal pumps. A total of 25 Rotaflow centrifugal pumps were used in these 9 patients, with the total circulatory support duration of 526 days. The median support period was 15 days (range;2-128 days). There were 2 cerebrovascular accidents and 1 Rotaflow pump circuit thrombosis during this period. Change from Rotaflow to Nipro VAD pump resulted in decrease in hematocrit by about 3 point. There was no difference in liver or renal function between before and after the pump change. Our results suggest that temporary use of Rotaflow centrifugal pump for recurrent pump thrombosis in patients with Nipro VADs may be a promising alternative.

Local diagnostic reference level based on size-specific dose estimates: assessment of pediatric abdominal/pelvic computed tomography at a Japanese national children's hospital.

BACKGROUND: A child's body size is not accurately reflected by volume CT dose index (CTDIvol) and dose-length product (DLP). Size-specific dose estimation (SSDE) was introduced recently as a new index of radiation dose. However, it has not yet been established as a diagnostic reference level (DRL). OBJECTIVE: To calculate the SSDE of abdominal/pelvic CT and compare the SSDE with CTDIvol. To calculate the DRLs of CTDIvol and SSDE. Our hypotheses are: SSDE values will be greater than CTDIvol, and our DRL will be smaller than the known DRLs of other countries. MATERIALS AND METHODS: The CTDIvol and DLP of 117 children who underwent abdominal/pelvic CT were collected retrospectively. The SSDE was calculated from the sum of the lateral and anteroposterior diameters. The relationships between body weight and effective diameter and between effective diameter and CTDIvol/SSDE were compared. Further, the local DRL was compared with the DRLs of other countries. RESULTS: Body weight and effective diameter and effective diameter and SSDE were positively correlated. In children ages 1, 5 and 10 years, the SSDE is closer to the exposure dose of CTDIvol for the 16-cm phantom, while in children ages 15 years, the SSDE falls between CTDIvol for the 16-cm phantom and that for the 32-cm phantom. The local DRL was lower than those of other countries. CONCLUSION: With SSDE, the radiation dose increased with increasing body weight. Since SSDE takes body size into account, it proved to be a useful indicator for estimating the exposure dose.

Automated measurement method for the determination of vitamin E in plasma lipoprotein classes.

In a subendothelial space of atherosclerotic arteries, apolipoprotein B-containing lipoproteins are accumulated and oxidized, and the oxidized lipoproteins promote macrophage foam cell formation. Therefore, the analysis of vitamin E, a major antioxidant in lipoproteins, is important for understanding atherosclerotic pathogenesis. A new method for the automated measurement of vitamin-E (γ- and α-tocopherols) in plasma HDL, LDL, and VLDL was established by using anion-exchange-chromatography for separation of lipoproteins, reverse-phase-chromatography for separation of γ- and α-tocopherols in each of lipoproteins, and fluorescent detection. The within-day assay and between-day assay coefficients of variation for lipoprotein tocopherol levels were 4.73-12.84% and 7.00-14.73%, respectively. The γ- and α-tocopherol/cholesterol ratios of VLDL were higher in healthy plasma than in plasma of untreated patients with dyslipidemia, but the ratios of LDL and HDL were not different. This new estimated method can provide the reliable data of lipoprotein vitamin-E and would be useful for the clinical settings.

Relevance of intermediate-density lipoprotein cholesterol to Framingham risk score of coronary heart disease in middle-aged men with increased non-HDL cholesterol.

BACKGROUND: Cholesterol levels of non-high-density lipoprotein (non-HDL), which contains low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), very low-density lipoprotein (VLDL) and chylomicron (CM) remnant, have been proven to perform a significant predictor of coronary heart disease (CHD) better than LDL-cholesterol regardless of triglyceride (TG) levels. The present study investigated the relevance of TG-rich lipoproteins (IDL, VLDL, CM) to Framingham risk score (FRS) predictive of 10-year CHD risk. METHODS: Lipoprotein profiles (cholesterol levels of HDL, LDL, IDL, VLDL, CM) in Japanese men (n = 487) who underwent medical check-up were determined by using our developed anion-exchange high performance liquid chromatography (AEX-HPLC). Total-cholesterol (TC), TG, fasting blood sugar (FBS) and hemoglobin (Hb) A1c were measured by routine methods. The lipoprotein profiles, non-HDL-cholesterol, TC, and TG were examined on these associations with FRS. RESULTS: The lipid levels except for CM-cholesterol were significantly different between two groups (low FRS, < 10%; high FRS, ≥10%) (P < 0.0001), and body mass index (BMI), TC, TG, IDL-, and VLDL-cholesterol were significantly and positively correlated with FRS. Among them, the significant association of non-HDL-cholesterol to FRS was noted (r = 0.411, P < 0.0001). Multiple stepwise regression analysis shows that, in addition to non-HDL-cholesterol, IDL-cholesterol in TG-rich lipoproteins was significantly correlated with FRS in independently of BMI. These correlation results were similarly found even when the part of the study subjects (n = 348) without the drug therapy for hyperlipidemia, diabetes, and hypertension was investigated. CONCLUSIONS: These results suggest that IDL-cholesterol may serve as a useful marker for CHD risk in Japanese men with increased non-HDL-cholesterol.

[Triglyceride (TG) and remnant lipoproteins].

Lowering low-density lipoprotein (LDL) cholesterol (LDL-C) can reduce the risk of cardiovascular disease (CVD) by approximately 30%, and the remaining 70% should be the second front of CVD risk reduction. Such residual risks include high triglyceride (TG) concentrations and low levels of high-density lipoprotein (HDL) cholesterol (HDL-C) in terms of dyslipidemia. TG-rich lipoproteins are heterogenous and composed of a variety of subfractions, all of which are not necessarily relevant to atherosclerosis and CVD risk. However, remnant lipoproteins, TG-rich lipoproteins, are atherogenic and related to CVD risk. Two different methods (RLP-C and RemL-C) have been developed to measure cholesterol levels of remnant lipoproteins. Although there is a difference in affinity to intermediate-density lipoprotein (IDL) between the two methods, they may be better qualified as biomarkers of CVD risk than TG itself. TG measurements play a certain role in the evaluation of CVD risk, but the remnant lipoprotein cholesterol measurement can provide better screening for patients at high CVD risk than TG and may be a useful examination in both quantity and quality.

Estimation of lipoprotein profile in patients with type II diabetes and its relevance to remnant lipoprotein cholesterol levels.

BACKGROUND: Remnant lipoprotein (RLP), associated with atherosclerosis progression, is often elevated in diabetes mellitus. The RLP level is estimated by immune-separation method and agarose-gel electrophoresis (AGE). METHODS: The patients were grouped into three groups according to tertile of RLP-cholesterol (RLP-C) levels. The lipoprotein profiles of type II diabetic patients (T2DM) (n=194) were measured by an anion-exchange liquid chromatography (AEX-HPLC) and an AGE with lipid-staining or cholesterol-staining. RESULTS: IDL- and VLDL-cholesterol by the AEX-HPLC, and VLDL-levels by the AGE with lipid-staining and with cholesterol-staining were significantly different in the three groups. In all the subjects, IDL-cholesterol (r=0.531) and VLDL-cholesterol (r=0.880) by the AEX-HPLC method were strongly correlated with RLP-C, but only VLDL levels were correlated with RLP-C in AGE, respectively. CONCLUSION: These results suggest that the AEX-HPLC, which can provide cholesterol levels of not only VLDL but also IDL, is helpful for estimation of lipid profiles in T2DM with high RLP-C.

Optimization of injection dose based on noise-equivalent count rate with use of an anthropomorphic pelvis phantom in three-dimensional 18F-FDG PET/CT.

The optimal injection dose for imaging of the pelvic region in 3D FDG PET tests was investigated based on the noise-equivalent count (NEC) rate with use of an anthropomorphic pelvis phantom. Count rates obtained from an anthropomorphic pelvis phantom were compared with those of pelvic images of 60 patients. The correlation between single photon count rates obtained from the pelvic regions of patients and the doses per body weight was also evaluated. The radioactivity at the maximum NEC rate was defined as an optimal injection dose, and the optimal injection dose for the body weight was evaluated. The image noise of a phantom was also investigated. Count rates obtained from an anthropomorphic pelvis phantom corresponded well with those from the human pelvis. The single photon count rate obtained from the phantom was 9.9 Mcps at the peak NEC rate. The coefficient of correlation between the single photon count rate and the dose per weight obtained from patient data was 0.830. The optimal injection doses for a patient with weighing 60 kg were estimated to be 375 MBq (6.25 MBq/kg) and 435 MBq (7.25 MBq/kg) for uptake periods of 60 and 90 min, respectively. The image noise was minimal at the peak NEC rate. We successfully estimated the optimal injection dose based on the NEC rate in the pelvic region on 3D FDG PET tests using an anthropomorphic pelvis phantom.

Redox-induced reversible metal assembly through translocation and reversible ligand coupling in tetranuclear metal sandwich frameworks.

Sandwich structures formed by metal atoms intercalated between sp(2)-carbon planes can be found either in metal-graphite-based materials or discrete multinuclear sandwich complexes. Their reactivity, and in particular their dynamic behaviour, has recently attracted interest both from a structural and a practical aspect, for example in catalysis. However, progress in this area has been rather slow, and it remains difficult to elucidate their structure and behaviour at the molecular level. Here, we report two sandwich complexes--in which four palladium centres are incorporated between two π-conjugated ligands--which exhibit two modes of redox-switchable structural changes. In the first complex, the tetrapalladium chain is split by oxidation into two well-separated dipalladium units. This motion is reversed on reduction. In the second complex, reversible carbon-carbon coupling occurs between the ligands during the redox process.

Formation and coordination modes of the C4E4 moiety (E = COOMe) bound to two palladium(II) moieties.

The transmetallation of the palladacyclopentadiene complex Pd{C(COOMe)C(COOMe)C(COOMe)C(COOMe)}(bipy) with the dicationic Pd(II) complex [Pd(bipy)(CH(3)CN)(2)][BF(4)](2) afforded a terminally σ-palladated diene complex [Pd(2){µ-η(1):η(1)-C(COOMe)C(COOMe)C(COOMe)C(COOMe)}(bipy)(2)(CH(3)CN)(2)][BF(4)](2). It was revealed by X-ray crystallographic analysis that replacement of the acetonitrile ligands in a terminally σ-palladated diene complex with PPh(3) ligands resulted in the conformation change of the σ-palladated diene moiety from skewed s-cis to planar s-trans. Treatment of a bis-triphenylphosphine dipalladium complex [Pd(2)(PPh(3))(2)(CH(3)CN)(4)][PF(6)](2) with dimethoxyacetylene dicarboxylate (DMAD) (1 equiv.) in acetonitrile resulted in the insertion of DMAD to the Pd-Pd bond to afford [Pd(2){µ-η(1):η(1)-C(COOMe)C(COOMe)}(PPh(3))(2)(CH(3)CN)(4)][PF(6)](2). Addition of the second DMAD gave the ylide-type complex [Pd(2){µ-η(2):η(3)-C(COOMe)C(COOMe)C(COOMe)C(COOMe)(PPh(3))}(PPh(3))(2)(CH(3)CN)(3)][PF(6)](2) of which the structure was determined by X-ray crystallographic analysis.

Effects of supervised aerobic exercise training on serum adiponectin and parameters of lipid and glucose metabolism in subjects with moderate dyslipidemia.

AIM: To examine the effects of supervised aerobic exercise training on serum adiponectin and lipids, including triglyceride (TG)-rich lipoproteins, in moderate dyslipidemic subjects. METHODS: Twenty-five dyslipidemic patients [mean body mass index (BMI)=24.6 kg/m²; mean age= 39 years; mean total cholesterol=226 mg/dL; mean TG=149 mg/dL] without metabolic syndrome, diabetes, and hypertension underwent supervised aerobic exercise training (60 min/day, 2 to 3 times/week) at an intensity of 60-80% of age-predicted maximal heart rate for 16 weeks. Lipoprotein cholesterol levels were measured by our established anion-exchange HPLC method. RESULTS: Aerobic exercise training significantly decreased BMI, cholesterol levels of LDL- and IDL-, and markedly reduced VLDL-cholesterol at week 8 (-45%) and week 16 (-50%), but changes in TG and HDL-cholesterol were not significant. Adiponectin significantly increased by 51% and HOMA-R was significantly decreased at week 16, although changes in these parameters were not significant at week 8. There was no significant relationship between changes in adiponectin and in VLDL- or IDL- cholesterol, but changes in adiponectin were inversely but insignificantly associated with changes in BMI (r=-0.343, p=0.095). CONCLUSIONS: These results suggest that supervised aerobic exercise training two to three times/week in the presence of body weight loss increases serum adiponectin with an improved lipid profile and insulin sensitivity at week 16 in non-obese moderate dyslipidemic patients, and that VLDL-cholesterol is markedly decreased by supervised aerobic exercise training.

Analysis of cholesterol levels in lipoprotein(a) with anion-exchange chromatography.

We previously established an analysis method for determining the cholesterol levels of five major lipoprotein classes [HDL, LDL, intermediate density lipoprotein (IDL), VLDL, and chylomicrons] in serum by an anion-exchange (AEX)-HPLC method, but lipoprotein(a) [Lp(a)], a well-known risk factor for atherosclerotic diseases, was not determinable. Therefore, we established new AEX-HPLC separation conditions for analyzing the cholesterol levels of six lipoprotein classes, including Lp(a). Serum lipoproteins were separated by HPLC with a diethylaminoethyl-ligand nonporous polymer-based column by elution with a stepwise gradient of the sodium perchlorate concentration. In this improved method, HDL, LDL, IDL, VLDL, chylomicrons, and Lp(a) were each eluted from the column. The cholesterol levels of the eluted lipoproteins were measured enzymatically by a postcolumn reaction. The within-day assay and between-day assay coefficients of variation for the lipoprotein cholesterol levels were in the ranges of 0.29-11.86% and 0.57-11.99%, respectively. The Lp(a) cholesterol levels determined by AEX-HPLC were significantly correlated with the amounts of Lp(a) protein measured by an immunoturbidimetry method available commercially (r = 0.9503, P < 0.0001). Taken together, this AEX-HPLC method may be effectively applied to the analysis of serum lipoproteins with high levels of Lp(a).

An anthropomorphic pelvis phantom for optimization of the diagnosis of lymph node metastases in the pelvis.

OBJECTIVE: An anthropomorphic pelvis phantom was made by the modification of a National Electrical Manufacturers Association (NEMA) phantom, currently the most popular one, and its clinical usefulness was evaluated. METHODS: The NEMA plus bone phantom was made by placing the pelvic bone model in the NEMA phantom. The NEMA plus bladder phantom was made by placing an imitation of the urinary bladder in the NEMA phantom. The pelvis phantom was also made by placing both the pelvic bone model and the bladder in the NEMA phantom. Four kinds of phantoms were imaged by both 2D and 3D dynamic modes, and for each phantom, prompt coincidence count rates, random ones, true plus scatter ones, and single photon rates were measured and these coincidence count rates were compared with those from the actual clinical data. After image reconstruction, the contrast ratio and image noise were also investigated. RESULTS: For the random coincidence count rate, the data obtained from each phantom showed good correspondence to the clinical data. The prompt coincidence count rates and true plus scatter ones of the clinical data were different from those obtained from NEMA phantom, NEMA plus bone one and NEMA plus bladder one, whereas there was a good correspondence between the data of the pelvis phantom and the clinical data. For the contrast ratio and image noise, there were discrepancies between the data of NEMA phantom and pelvis phantoms. CONCLUSIONS: We made an anthropomorphic pelvis phantom by the simple modification of a NEMA phantom. This phantom showed performance similar to that of the actual human pelvis, suggesting clinical usefulness in the evaluation of new acquisition protocols and reconstruction algorithms.