Tumors use many strategies to evade the immune system. A new study adds a new trick to the list-inhibiting the migration of dendritic cells from tumors toward lymph nodes (pages 98-105).
Cardiomyocytes can be sorted to high purity upon staining them with a dye that labels mitochondria. This permits the preparation of pure populations of cardiomyocytes differentiated from stem cells.
BACKGROUND: To compare the median overall survival of patients with isolated nonresectable liver metastases in comparable groups of patients treated with either isolated hepatic perfusion (IHP)... Show moreBACKGROUND: To compare the median overall survival of patients with isolated nonresectable liver metastases in comparable groups of patients treated with either isolated hepatic perfusion (IHP) with melphalan or systemic chemotherapy. PATIENTS AND METHODS: Colorectal cancer patients with isolated liver metastases, who underwent IHP, were included in this study. The control group consisted of a subgroup of colorectal cancer patients with liver metastases only, who were enrolled in the randomized CApecitabine, IRinotecan, Oxaliplatin (CAIRO) phase III study. RESULTS: Ninety-nine patients were treated with IHP, and 111 patients were included in the control group. All patient characteristics were comparable except for age. Median follow-up was 78.1 months for IHP versus 54.7 months in the control group. Median overall survival was 25.0 [95% confidence interval (CI) 19.4-30.6] months for IHP and 21.7 (95% CI 19.6-23.8) months for systemic treatment and did not differ significantly (P = 0.29). Treatment-related mortality was 2% for the systemic treatment and 6% for IHP (P = 0.11). CONCLUSION: Compared with a patient group with comparable characteristics treated with systemic chemotherapy, IHP does not provide a benefit in overall survival in patients with isolated nonresectable colorectal liver metastases. Currently, the use of IHP cannot be advocated outside the scope of clinical studies. Show less
Decision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision... Show moreDecision-making involves the ability to choose between competing actions that are associated with uncertain benefits and penalties. The Iowa Gambling Task (IGT), which mimics real-life decision-making, involves learning a reward-punishment rule over multiple trials. Patients with damage to ventromedial prefrontal cortex (VMPFC) show deficits learning these rules, although this performance deficit is not exclusively associated with VMPFC damage. In this study, we used functional Magnetic Resonance Imaging (fMRI) to study the roles of prefrontal cortex regions involved in rule learning and rule application in healthy adults using an adapted version of the Iowa Gambling Task. Participants (N=20) were asked to infer rules over series of 16 trials in a two-deck card game. Rewards were given on each trial and punishment was unpredictable. For half of the series, those decks that gave high rewards were also better decks in the long run. For the other half of the series, the decks that gave low rewards were better decks in the long run. Behaviorally, participants started to differentiate between advantageous and disadvantageous decks after approximately four/six trials, and learning occurred faster for high-reward decks. Lateral PFC (lat-PFC) and Anterior Cingulate Coretex (ACC)/pre-supplementary motor area (pre-SMA) were most active for early decisions, whereas medial orbital frontal cortex (med-OFC) was most active for decisions made later in the series. These results suggest that lat-PFC and ACC/pre-SMA are important for directing behavior towards long-term goals, whereas med-OFC represents reward values towards which behavior should be directed. Show less
Klok, F.A.; Bijl, N. van der; Eikenboom, H.C.J.; Rooden, C.J. van; Roos, A. de; Kroft, L.J.M.; Huisman, M.V. 2010
AIM OF THE STUDY: In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the... Show moreAIM OF THE STUDY: In patients from the Dutch TME trial patterns of local recurrence (LR) in rectal cancer were studied. The purpose was to reconstruct the most likely mechanisms of LR and the effect of preoperative radiotherapy. METHODS: 1417 patients were analyzed; 713 were randomized into preoperative radiotherapy and total mesorectal excision (RT + TME), 704 into TME alone. Of the 114 patients with LR, the subsites of LR were determined and related to tumor and treatment factors. RESULTS: Overall 5-year LR-rate was 4.6% in the RT + TME group and 11.0% in the TME group. Presacral local recurrences occurred most in both groups. Radiotherapy reduced anastomotic LR significantly, except when after low anterior resection (LAR) distal margins were less than 5 mm. Abdominoperineal resection (APR) mainly resulted in presacral LR. Even after resection with a negative circumferential resection margin, LR-rates were high. Thirty percent of the patients had advanced tumors, which resulted in 58% of all LRs. Lateral LR comprised 20% of all LR. Presacral and lateral LR resulted in a poor prognosis, in contrast to anterior or anastomotic LRs with a relatively good prognosis. CONCLUSIONS: RT reduces LR in all subsites and is especially effective in preventing anastomotic LR after LAR. APR-surgery mainly results in presacral LR, which may be prevented by a wider resection. In the TME trial many advanced tumors were included, rather requiring chemoradiotherapy instead of RT. Currently, with good imaging techniques, better selection can take place. Especially lateral LR might be a problem in the future. Show less
Wauben, M.H.M.; Toes, R.E.M.; Bos, N.A.; Damoiseaux, J.; Ham, S.M. van; Loosdrecht, A.A. van de; Samsom, J.N. 2010
The purpose of this study was to assess the performance of 0.5 versus 3.0 mm slice reconstructions in depicting coronary calcium with special attention to patients having zero calcium scores at 3.0... Show moreThe purpose of this study was to assess the performance of 0.5 versus 3.0 mm slice reconstructions in depicting coronary calcium with special attention to patients having zero calcium scores at 3.0 mm reconstructions by using computed tomography (CT). Imaging was performed by volumetric 320-detector row CT. Scans of 100 patients with a negative and 100 patients with a positive Agatston score at 3.0 mm reconstructions were consecutively selected. Non-overlapping volume sets with 3.0 and 0.5 mm slice thickness were reconstructed from the same raw data and Agatston and volume scores were obtained. The Wilcoxon signed ranks test was used to determine statistical differences between 3.0 and 0.5 mm calcium scores. Agatston and volume scores obtained at 0.5 mm were significantly higher than at 3.0 mm reconstructions (mean Agatston score: 266 +/- 495 vs. 231 +/- 461. Mean volume score: 223 +/- 399 vs. 206 +/- 385, both P < 0.01). In 21% of patients with zero 3.0 mm Agatston scores, a positive Agatston and/or volume score was found at 0.5 mm reconstructions. With volumetric 320-detector row CT, prospective ECG-triggered calcium scoring at 0.5 mm compared to 3.0 mm reconstructions leads to an increase in Agatston and volume scores and small amounts of coronary calcium are earlier depicted. This may be of special interest in patients with zero calcium scores with traditional 3.0 mm measures, where 0.5 mm reconstructions may help in superior depicting or ruling out coronary artery disease. Show less
Wardenaar, K.J.; Veen, T. van; Giltay, E.J.; Hollander-Gijsman, M. den; Penninx, B.W.J.H.; Zitman, F.G. 2010
BACKGROUND: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality... Show moreBACKGROUND: The Inventory of Depressive Symptomatology Self Report (IDS-SR) is a widely used but heterogeneous measure of depression severity. Insight in its factor structure and dimensionality could help to develop more homogeneous IDS-SR subscales. However previous factoranalytical studies have found mixed results. Therefore, the present study tested which factor structure underlies the IDS-SR and, in addition, if the factors can be used as unidimensional subscales. METHODS: Confirmatory factor analysis (CFA) was done to identify the best-fitting factor structure. The study sample consisted of 2600 individuals (mean age 40.5+/-12.1). We assessed model fit in 4 groups: 957 Major Depressive Disorder (MDD) patients, 450 remitted MDD patients, 570 patients with an anxiety disorder and 623 healthy controls to test the consistency of model fit. Rasch analyses in the full sample were used to evaluate and optimize the unidimensionality and psychometric quality of the factors. RESULTS: CFA indicated that a 3-factor model fits the IDS-SR data best and is consistent across groups, with a 'mood/cognition' factor, an 'anxiety/arousal' factor and a 'sleep' factor. In addition, Rasch analyses indicated that the 'mood/cognition' and 'anxiety/arousal' factors could be optimized to be used as unidimensional subscales. LIMITATIONS: The fit of only 4 models was tested, ranging from a 1- to 4-factor model. CONCLUSIONS: The IDS-SR is a heterogeneous instrument with a multifactorial underlying structure. It is possible to measure more homogeneous symptomatology with IDS-SR subscales, which could be useful in clinical practice and scientific research. Show less
Aims Multidetector computed tomography coronary angiography (CTA) has emerged as a feasible imaging modality for non-invasive assessment of coronary artery disease (CAD). Recently, 320-row CTA... Show moreAims Multidetector computed tomography coronary angiography (CTA) has emerged as a feasible imaging modality for non-invasive assessment of coronary artery disease (CAD). Recently, 320-row CTA systems were introduced, with 16 cm anatomical coverage, allowing image acquisition of the entire heart within a single heart beat. The aim of the present study was to assess the diagnostic accuracy of 320-row CTA in patients with known or suspected CAD. Methods and results A total of 64 patients (34 male, mean age 61 +/- 16 years) underwent CTA and invasive coronary angiography. All CTA scans were evaluated for the presence of obstructive coronary stenosis by a blinded expert, and results were compared with quantitative coronary angiography. Four patients were excluded from initial analysis due to non-diagnostic image quality. Sensitivity, specificity, and positive and negative predictive values to detect >/=50% luminal narrowing on a patient basis were 100, 88, 92, and 100%, respectively. Moreover, sensitivity, specificity, and positive and negative predictive values to detect >/=70% luminal narrowing on a patient basis were 94, 95, 88, and 98%, respectively. With inclusion of non-diagnostic imaging studies, sensitivity, specificity, and positive and negative predictive values to detect >/=50% luminal narrowing on a patient basis were 100, 81, 88, and 100%, respectively. Conclusion The current study shows that 320-row CTA allows accurate non-invasive assessment of significant CAD. Show less
Noorden, M.S. van; Giltay, E.J.; Hollander-Gijsman, M.E. den; Wee, N.J.A. van der; Veen, T. van; Zitman, F.G. 2010
BACKGROUND: No previous large scale studies have assessed gender differences in naturalistic samples of major depressive disorder (MDD) outpatients. We therefore determined gender differences in... Show moreBACKGROUND: No previous large scale studies have assessed gender differences in naturalistic samples of major depressive disorder (MDD) outpatients. We therefore determined gender differences in comorbidity, symptom patterns and subjective health status in these outpatients in a mental healthcare setting. METHODS: Of 3798 consecutive adult patients (age range: 18-65), 1131 (65.1% women) fulfilled DSM-IV criteria of current MDD on the Mini-International Neuropsychiatric Interview (MINI-Plus). Patients were routinely assessed with Routine Outcome Monitoring (ROM), including the Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI) and Short Form-36 (SF-36). RESULTS: No gender differences were found in disease severity using the clinician-rated MADRS. However, women showed a significant higher depression severity measured with the self-report BDI-II. Also, psychopathological symptoms self-reported with the BSI were higher, and reported health status on the SF-36 was lower in women. In men with MDD, social phobia, attention deficit hyperactivity disorder, and alcohol and drug misconduct were more common comorbid disorders, while in women with MDD posttraumatic stress disorder and bulimia nervosa were more common, as well as atypical features of depression. LIMITATIONS: The use of retrospective reports of lifetime psychopathology might have led to recall bias. 20% of subjects were excluded from ROM due to language problems or logistical reasons. CONCLUSIONS: Although women self-reported higher depression severity, more severe general psychopathological symptoms and lower health status, no differences in disease severity were found on interviewer ratings. These findings could have implications for clinical decision making and treatment. Show less