Does normalized signal intensity of cervical discs on T2 weighted MRI images change in whiplash patients?

PURPOSE We tested the hypothesis that whiplash trauma leads to changes of the signal intensity of cervical discs in T2-weighted images. METHODS AND MATERIALS 50 whiplash patients (18-65 years) were examined within 48h after motor vehicle accident, and again after 3 and 6 months and compared to 50 age- and sex-matched controls. Signal intensity in ROI's of the discs at the levels C2/3 to C7/T1 and the adjacent vertebral bodies were measured on sagittal T2 weighted MR images and normalized using the average of ROI's in fat tissue. The contrast between discs and both adjacent vertebrae was calculated and disc degeneration was graded by the Pfirrmann-grading system. RESULTS Whiplash trauma did not have a significant effect on the normalized signals from discs and vertebrae, on the contrast between discs and adjacent vertebrae, or on the Pfirrmann grading. However, the contrast between discs and adjacent vertebrae and the Pfirrmann grading showed a strong correlation. In healthy volunteers, the contrast between discs and adjacent vertebrae and Pfirrmann grading increased with age and was dependent on the disc level. CONCLUSION We could not find any trauma related changes of cervical disc signal intensities. Normalized signals of discs and Pfirrmann grading changed with age and varied between disc levels with the used MR sequence.

Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive-stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK 15/08)

INTRODUCTION Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. METHODS Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. RESULTS Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. CONCLUSIONS This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404.

Loss of TRAIL-receptors is a recurrent feature in pancreatic cancer and determines the prognosis of patients with no nodal metastasis after surgery

INTRODUCTION Agonistic antibodies targeting TRAIL-receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are being developed as a novel therapeutic approach in cancer therapy including pancreatic cancer. However, the cellular distribution of these receptors in primary pancreatic cancer samples has not been sufficiently investigated and no study has yet addressed the issue of their prognostic significance in this tumor entity. AIMS AND METHODS Applying tissue microarray (TMA) analysis, we performed an immunohistochemical assessment of TRAIL-receptors in surgical samples from 84 consecutive patients affected by pancreatic adenocarcinoma and in 26 additional selected specimens from patients with no lymph nodes metastasis at the time of surgery. The prognostic significance of membrane staining and staining intensity for TRAIL-receptors was evaluated. RESULTS The fraction of pancreatic cancer samples with positive membrane staining for TRAIL-R1 and TRAIL-R2 was lower than that of cells from surrounding non-tumor tissues (TRAIL-R1: p<0.001, TRAIL-R2: p = 0.006). In addition, subgroup analyses showed that loss of membrane staining for TRAIL-R2 was associated with poorer prognosis in patients without nodal metastases (multivariate Cox regression analysis, Hazard Ratio: 0.44 [95% confidence interval: 0.22-0.87]; p = 0.019). In contrast, analysis of decoy receptors TRAIL-R3 and -R4 in tumor samples showed an exclusively cytoplasmatic staining pattern and no prognostic relevance. CONCLUSION This is a first report on the prognostic significance of TRAIL-receptors expression in pancreatic cancer showing that TRAIL-R2 might represent a prognostic marker for patients with early stage disease. In addition, our data suggest that loss of membrane-bound TRAIL-receptors could represent a molecular mechanism for therapeutic failure upon administration of TRAIL-receptors-targeting antibodies in pancreatic cancer. This hypothesis should be evaluated in future clinical trials.

Effects of arm training with the robotic device ARMin I in chronic stroke: three single cases

BACKGROUND: Several clinical studies on chronic stroke conducted with end-effector-based robots showed improvement of the motor function in the affected arm. Compared to end-effector-based robots, exoskeleton robots provide improved guidance of the human limb and are better suited to train task-oriented movements with a large range of motions. OBJECTIVE: To test whether intensive arm training with the arm exoskeleton ARMin I is feasible with chronic-stroke patients and whether it improves motor function in the paretic arm. METHODS: Three single cases with chronic hemiparesis resulting from unilateral stroke (at least 14 months after stroke). A-B design with 2 weeks of multiple baseline measurements (A), 8 weeks of training (B) with repetitive measurements and a follow-up measurement 8 weeks after training. The training included shoulder and elbow movements with the robotic rehabilitation device ARMin I. Two subjects had three 1-hour sessions per week and 1 subject received five 1-hour sessions per week. The main outcome measurement was the upper-limb part of the Fugl-Meyer Assessment (FMA). RESULTS: The ARMin training was well tolerated by the patients, and the FMA showed moderate, but significant improvements for all 3 subjects (p < 0.05). Most improvements were maintained 8 weeks after discharge. CONCLUSIONS: This study indicates that intensive training with an arm exoskeleton is feasible with chronic-stroke patients. Moderate improvements were found in all 3 subjects, thus further clinical investigations are justified.

Gadoxetate uptake as a possible marker of hepatocyte damage after liver resection-preliminary data

AIM: To determine the feasibility of evaluating surgically induced hepatocyte damage using gadoxetate disodium (Gd-EOB-DTPA) as a marker for viable hepatocytes at magnetic resonance imaging (MRI) after liver resection. MATERIAL AND METHODS: Fifteen patients were prospectively enrolled in this institutional review board-approved study prior to elective liver resection after informed consent. Three Tesla MRI was performed 3-7 days after surgery. Three-dimensional (3D) T1-weighted (W) volumetric interpolated breath-hold gradient echo (VIBE) sequences covering the liver were acquired before and 20 min after Gd-EOB-DTPA administration. The signal-to-noise ratio (SNR) was used to compare the uptake of Gd-EOB-DTPA in healthy liver tissue and in liver tissue adjacent to the resection border applying paired Student's t-test. Correlations with potential influencing factors (blood loss, duration of intervention, age, pre-existing liver diseases, postoperative change of resection surface) were calculated using Pearson's correlation coefficient. RESULTS: Before Gd-EOB-DTPA administration the SNR did not differ significantly (p = 0.052) between healthy liver tissue adjacent to untouched liver borders [59.55 ± 25.46 (SD)] and the liver tissue compartment close to the resection surface (63.31 ± 27.24). During the hepatocyte-specific phase, the surgical site showed a significantly (p = 0.04) lower SNR (69.44 ± 24.23) compared to the healthy site (78.45 ± 27.71). Dynamic analyses revealed a significantly lower increase (p = 0.008) in signal intensity in the healthy tissue compared to the resection border compartment. CONCLUSION: EOB-DTPA-enhanced MRI may have the potential to be an effective non-invasive tool for detecting hepatocyte damage after liver resection.

Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study

AIM The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phenotype in non-infarct-related arteries of STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS Between September 2009 and January 2011, 103 STEMI patients underwent intravascular ultrasonography (IVUS) and radiofrequency ultrasonography (RF-IVUS) of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end-point was the change in per cent atheroma volume (PAV). After 13 months, low-density lipoprotein cholesterol (LDL-C) had decreased from a median of 3.29 to 1.89 mmol/L (P < 0.001), and high-density lipoprotein cholesterol (HDL-C) levels had increased from 1.10 to 1.20 mmol/L (P < 0.001). PAV of the non-IRA decreased by -0.9% (95% CI: -1.56 to -0.25, P = 0.007). Patients with regression in at least one non-IRA were more common (74%) than those without (26%). Per cent necrotic core remained unchanged (-0.05%, 95% CI: -1.05 to 0.96%, P = 0.93) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116, P = 0.15). CONCLUSION High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients.

Peak Last Glacial weathering intensity on the North American continent recorded by the authigenic Hf isotope composition of North Atlantic deep-sea sediments

We have retrieved radiogenic hafnium (Hf) isotope compositions (ɛHf) from authigenic Fe–Mn oxyhydroxides of deep northwest Atlantic sediments deposited over the past 26 ka to investigate the oceanic evidence of changes in dissolved weathering inputs from NE America during the last deglaciation. The extraction of seawater-derived Hf isotopic compositions from Fe–Mn oxyhydroxides is not a standard procedure. Comparisons between the Al/Hf ratios and Hf isotopic compositions of the chemically extracted authigenic phase on the one hand, and those of the corresponding detrital fractions on the other, provide evidence that the composition of past seawater has been reliably obtained for most sampled depths with our leaching procedures. This is endorsed most strongly by data for a sediment core from 4250 m water depth at the deeper Blake Ridge, for which consistent replicates were produced throughout. The Hf isotopic composition of the most recent sample in this core also closely matches that of nearby present day central North Atlantic seawater. Comparison with previously published seawater Nd and Pb isotope compositions obtained on the same cores shows that both Hf and Pb were released incongruently during incipient chemical weathering, but responded differently to the deglacial retreat of the Laurentide Ice Sheet. Hafnium was released more congruently during peak glacial conditions of the Last Glacial Maximum (LGM) and changed to typical incongruent interglacial ɛHf signatures either during or shortly after the LGM. This indicates that some zircon-derived Hf was released to seawater during the LGM. Conversely, there is no clear evidence for an increase in the influence of weathering of Lu-rich mineral phases during deglaciation, possibly since relatively unradiogenic Hf contributions from feldspar weathering were superimposed. While the authigenic Pb isotope signal in the same marine sediment samples traced peak chemical weathering rates on continental North America during the transition to the Holocene a similar incongruent excursion is notably absent in the Hf isotope record. The early change towards more radiogenic ɛHf in relation to the LGM may provide direct evidence for the transition from a cold-based to a warm-based Laurentide Ice Sheet on the Atlantic sector of North America.

Long-term stability of contour augmentation in the esthetic zone: histologic and histomorphometric evaluation of 12 human biopsies 14 to 80 months after augmentation.

BACKGROUND Contour augmentation around early-placed implants (Type 2 placement) using autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) and a collagen barrier membrane has been documented to predictably provide esthetically satisfactory clinical outcomes. In addition, recent data from cone beam computed tomography studies have shown the augmented volume to be stable long-term. However, no human histologic data are available to document the tissue reactions to this bone augmentation procedure. METHODS Over an 8-year period, 12 biopsies were harvested 14 to 80 months after implant placement with simultaneous contour augmentation in 10 patients. The biopsies were subjected to histologic and histomorphometric analysis. RESULTS The biopsies consisted of 32.0% ± 9.6% DBBM particles and 40.6% ± 14.6% mature bone. 70.3% ± 14.5% of the DBBM particle surfaces were covered with bone. On the remaining surface, multinucleated giant cells with varying intensity of tartrate-resistant acid phosphatase staining were regularly present. No signs of inflammation were visible, and no tendency toward a decreasing volume fraction of DBBM over time was observed. CONCLUSIONS The present study confirms previous findings that osseointegrated DBBM particles do not tend to undergo substitution over time. This low substitution rate may be the reason behind the clinically and radiographically documented long-term stability of contour augmentation using a combination of autogenous bone chips, DBBM particles, and a collagen membrane.

Psychological interventions for acute pain after open heart surgery

BACKGROUND Acute postoperative pain is one of the most disturbing complaints in open heart surgery, and is associated with a risk of negative consequences. Several trials investigated the effects of psychological interventions to reduce acute postoperative pain and improve the course of physical and psychological recovery of participants undergoing open heart surgery. OBJECTIVES To compare the efficacy of psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery on pain, pain medication, mental distress, mobility, and time to extubation. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE (1946 to September 2013), EMBASE (1980 to September 2013), Web of Science (all years to September 2013), and PsycINFO (all years to September 2013) for eligible studies. We used the 'related articles' and 'cited by' options of eligible studies to identify additional relevant studies. We also checked lists of references of relevant articles and previous reviews. We also searched the ProQuest Dissertations and Theses Full Text Database (all years to September 2013) and contacted the authors of primary studies to identify any unpublished material. SELECTION CRITERIA Randomised controlled trials comparing psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery. DATA COLLECTION AND ANALYSIS Two review authors (SK and JR) independently assessed trials for eligibility, estimated the risk of bias and extracted all data. We calculated effect sizes for each comparison (Hedges' g) and meta-analysed data using a random-effects model. MAIN RESULTS Nineteen trials were included (2164 participants).No study reported data on the number of participants with pain intensity reduction of at least 50% from baseline. Only one study reported data on the number of participants below 30/100 mm on the Visual Analogue Scale (VAS) in pain intensity. Psychological interventions have no beneficial effects in reducing pain intensity measured with continuous scales in the medium-term interval (g -0.02, 95% CI -0.24 to 0.20, 4 studies, 413 participants, moderate quality evidence) nor in the long-term interval (g 0.12, 95% CI -0.09 to 0.33, 3 studies, 280 participants, low quality evidence).No study reported data on median time to remedication or on number of participants remedicated. Only one study provided data on postoperative analgesic use. Studies reporting data on mental distress in the medium-term interval revealed a small beneficial effect of psychological interventions (g 0.36, 95% CI 0.10 to 0.62, 12 studies, 1144 participants, low quality evidence). Likewise, a small beneficial effect of psychological interventions on mental distress was obtained in the long-term interval (g 0.28, 95% CI 0.05 to 0.51, 11 studies, 1320 participants, low quality evidence). There were no beneficial effects of psychological interventions on mobility in the medium-term interval (g 0.23, 95% CI -0.22 to 0.67, 3 studies, 444 participants, low quality evidence) nor in the long-term interval (g 0.29, 95% CI -0.14 to 0.71, 4 studies, 423 participants, low quality evidence). Only one study reported data on time to extubation. AUTHORS' CONCLUSIONS For the majority of outcomes (two-thirds) we could not perform a meta-analysis since outcomes were not measured, or data were provided by one trial only. Psychological interventions have no beneficial effects on reducing postoperative pain intensity or enhancing mobility. There is low quality evidence that psychological interventions reduce postoperative mental distress. Due to limitations in methodological quality, a small number of studies, and large heterogeneity, we rated the quality of the body of evidence as low. Future trials should measure crucial outcomes (e.g. number of participants with pain intensity reduction of at least 50% from baseline) and should focus to enhance the quality of the body of evidence in general. Altogether, the current evidence does not clearly support the use of psychological interventions to reduce pain in participants undergoing open heart surgery.

Incidence and Imaging Outcomes of Acute Scaffold Disruption and Late Structural Discontinuity After Implantation of the Absorb Everolimus-Eluting Fully Bioresorbable Vascular Scaffold: Optical Coherence Tomography Assessment in the ABSORB Cohort B Trial (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions).

OBJECTIVES This study sought to describe the frequency and clinical impact of acute scaffold disruption and late strut discontinuity of the second-generation Absorb bioresorbable polymeric vascular scaffolds (Absorb BVS, Abbott Vascular, Santa Clara, California) in the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) cohort B study by optical coherence tomography (OCT) post-procedure and at 6, 12, 24, and 36 months. BACKGROUND Fully bioresorbable scaffolds are a novel approach to treatment for coronary narrowing that provides transient vessel support with drug delivery capability without the long-term limitations of metallic drug-eluting stents. However, a potential drawback of the bioresorbable scaffold is the potential for disruption of the strut network when overexpanded. Conversely, the structural discontinuity of the polymeric struts at a late stage is a biologically programmed fate of the scaffold during the course of bioresorption. METHODS The ABSORB cohort B trial is a multicenter single-arm trial assessing the safety and performance of the Absorb BVS in the treatment of 101 patients with de novo native coronary artery lesions. The current analysis included 51 patients with 143 OCT pullbacks who underwent OCT at baseline and follow-up. The presence of acute disruption or late discontinuities was diagnosed by the presence on OCT of stacked, overhung struts or isolated intraluminal struts disconnected from the expected circularity of the device. RESULTS Of 51 patients with OCT imaging post-procedure, acute scaffold disruption was observed in 2 patients (3.9%), which could be related to overexpansion of the scaffold at the time of implantation. One patient had a target lesion revascularization that was presumably related to the disruption. Of 49 patients without acute disruption, late discontinuities were observed in 21 patients. There were no major adverse cardiac events associated with this finding except for 1 patient who had a non-ischemia-driven target lesion revascularization. CONCLUSIONS Acute scaffold disruption is a rare iatrogenic phenomenon that has been anecdotally associated with anginal symptoms, whereas late strut discontinuity is observed in approximately 40% of patients and could be viewed as a serendipitous OCT finding of a normal bioresorption process without clinical implications. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856).

Quality of life after pulmonary embolism: validation of the French version of the PEmb-QoL questionnaire.

BackgroundThe PEmb-QoL is a validated 40-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It covers six health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in Dutch and English, we sought to prospectively validate the psychometric properties of a French version of the PEmb-QoL.MethodsWe performed a forward and backward translation of the English version of the PEmb-QoL into French. French-speaking consecutive adult patients with an acute, objectively confirmed PE admitted to the emergency department of a Swiss university hospital between 08/2009 and 09/2011 were recruited telephonically. We used standard psychometric tests and criteria to evaluate the acceptability, reliability, and validity of the French version of the PEmb-QoL. We also performed an exploratory factor analysis.ResultsOverall, 102 patients were enrolled in the study. The French version of the PEmb-QoL showed good reliability (internal consistency, item¿total and inter-item correlations), reproducibility (test-retest reliability), and validity (convergent, discriminant) in French-speaking patients with PE. The exploratory factor analysis suggested three underlying dimensions: limitations in daily activity (items 4b-m, 5a-d), symptoms (items 1a-h and 7), and emotional complaints (items 9a-f and j).ConclusionWe successfully validated the French version of the PEmb-QoL questionnaire in patients with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French-speaking patients.

Beta-alanine supplementation improves jumping power and affects severe-intensity performance in professional alpine skiers.

INTRODUCTION Supplementation with beta-alanine may have positive effects on severe-intensity, intermittent, and isometric strength-endurance performance. These could be advantageous for competitive alpine skiers, whose races last 45 to 150 s, require metabolic power above the aerobic maximum, and involve isometric muscle work. Further, beta-alanine supplementation affects the muscle force-frequency relationship, which could influence explosiveness. We explored the effects of beta-alanine on explosive jump performance, severe exercise energy metabolism, and severe-intensity ski-like performance. METHODS Nine male elite alpine skiers consumed 4.8 g/d beta-alanine or placebo for 5 weeks in a double-blind fashion. Before and after, they performed countermovement jumps (CMJ), a 90-s cycling bout at 110% VO2max (CLT), and a maximal 90-s box jump test (BJ90). RESULTS Beta-alanine improved maximal (+7 ± 3%, d = 0.9) and mean CMJ power (+7 ± 2%, d = 0.7), tended to reduce oxygen deficit (-3 ± 8%, p = .06) and lactate accumulation (-12 ± 31%) and enhance aerobic energy contribution (+1.3 ± 2.9%, p = .07) in the CLT, and improved performance in the last third of BJ90 (+7 ± 4%, p = .02). These effects were not observed with placebo. CONCLUSIONS Beta-alanine supplementation improved explosive and repeated jump performance in elite alpine skiers. Enhanced muscle contractility could possibly explain improved explosive and repeated jump performance. Increased aerobic energy production could possibly help explain repeated jump performance as well.

Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy

BACKGROUND To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse. PATIENTS AND METHODS In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate. RESULTS Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%). CONCLUSIONS Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients.

Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019)

BACKGROUND Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa-the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)-includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort. OBJECTIVE Describe survival outcomes, along with current treatment standards and factors associated with prognosis, to inform future trial design in this patient group. DESIGN, SETTING, AND PARTICIPANTS STAMPEDE trial control arm comprising men newly diagnosed with M1 disease who were recruited between October 2005 and January 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Overall survival (OS) and failure-free survival (FFS) were reported by primary disease characteristics using Kaplan-Meier methods. Hazard ratios and 95% confidence intervals (CIs) were derived from multivariate Cox models. RESULTS AND LIMITATIONS A cohort of 917 men with newly diagnosed M1 disease was recruited to the control arm in the specified interval. Median follow-up was 20 mo. Median age at randomisation was 66 yr (interquartile range [IQR]: 61-71), and median prostate-specific antigen level was 112 ng/ml (IQR: 34-373). Most men (n=574; 62%) had bone-only metastases, whereas 237 (26%) had both bone and soft tissue metastases; soft tissue metastasis was found mainly in distant lymph nodes. There were 238 deaths, 202 (85%) from PCa. Median FFS was 11 mo; 2-yr FFS was 29% (95% CI, 25-33). Median OS was 42 mo; 2-yr OS was 72% (95% CI, 68-76). Survival time was influenced by performance status, age, Gleason score, and metastases distribution. Median survival after FFS event was 22 mo. Trial eligibility criteria meant men were younger and fitter than general PCa population. CONCLUSIONS Survival remains disappointing in men presenting with M1 disease who are started on only long-term ADT, despite active treatments being available at first failure of ADT. Importantly, men with M1 disease now spend the majority of their remaining life in a state of castration-resistant relapse. PATIENT SUMMARY Results from this control arm cohort found survival is relatively short and highly influenced by patient age, fitness, and where prostate cancer has spread in the body.

Neutrophil expression of ICAM1, CXCR1, and VEGFR1 in patients with breast cancer before and after adjuvant chemotherapy

BACKGROUND Distinct populations of neutrophils have been identified based on the expression of intercellular adhesion molecule 1 (ICAM1, CD54) and chemokine receptor 1 (CXCR1, interleukin 8 receptor α). AIM We analyzed the expression of vascular endothelial growth factor receptor 1 (VEGFR1), a physiological negative regulator of angiogenesis, on distinct populations of neutrophils from the blood of patients before and after adjuvant chemotherapy for breast cancer. MATERIALS AND METHODS Neutrophil populations were distinguished as reverse transmigrated (ICAM1(high)/CXCR1(low)), naïve (ICAM1(low)/CXCR1(high)), or tissue-resident neutrophils (ICAM1(low)/CXCR1(low)), and their VEGFR1 expression quantified. RESULTS Reverse transmigrated ICAM1(high)/CXCR1(low) neutrophilic granulocytes decreased significantly after chemotherapy and these were also the cells with highest mean fluorescence intensity for VEGFR1. CONCLUSION Chemotherapy mainly reduces the number of reverse transmigrated long-lived ICAM1(high)/CXCR1(low) VEGFR1-expressing neutrophils. The decrease of antiangiogenic VEGFR1 may have a potential impact on tumour angiogenesis in patients undergoing adjuvant chemotherapy.