Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

The effects of vagus nerve stimulation on tryptophan metabolites in children with intractable epilepsy.

BACKGROUND: The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. METHODS: Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n=21), while the other half received low-output (active control) stimulation (n=20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. RESULTS: Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p=0.002) and correlated significantly with improvement of mood (τ=-0.39, p=0.037) and seizure frequency reduction (τ=-0.33, p<0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. CONCLUSION: Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.

Transperineal ultrasound compared to evacuation proctography for diagnosing enteroceles and intussusceptions.

INTRODUCTION: This study concerns the level of agreement between transperineal ultrasound and evacuation proctography for diagnosing enteroceles and intussusceptions. METHOD: In a prospective observational study, 50 consecutive women who were planned to have an evacuation proctography underwent transperineal ultrasound too. Sensitivity, specificity, positive (PPV) and negative predictive value, as well as the positive and negative likelihood ratio of transperineal ultrasound were assessed in comparison to evacuation proctography. To determine the interobserver agreement of transperineal ultrasound, the quadratic weighted kappa was calculated. Furthermore, receiver operating characteristic curves were generated to show the diagnostic capability of transperineal ultrasound. RESULTS: For diagnosing intussusceptions (PPV 1.00), a positive finding on transperineal ultrasound was predictive of an abnormal evacuation proctography. Sensitivity of transperineal ultrasound was poor for intussusceptions (0.25). For diagnosing enteroceles, the positive likelihood ratio was 2.10 and the negative likelihood ratio, 0.85. There are many false-positive findings of enteroceles on ultrasonography (PPV 0.29). The interobserver agreement of the two ultrasonographers assessed as the quadratic weighted kappa of diagnosing enteroceles was 0.44 and that of diagnosing intussusceptions was 0.23. CONCLUSION: An intussusception on ultrasound is predictive of an abnormal evacuation proctography. For diagnosing enteroceles, the diagnostic quality of transperineal ultrasound was limited compared to evacuation proctography.

Comparison of two scoring systems for diagnosing levator ani muscle damage.

INTRODUCTION AND HYPOTHESIS: Levator defects are risk factors for pelvic organ prolapse (POP) and its recurrence. The most widely used scoring systems for severity of defects shown on magnetic resonance imaging (MRI) and perineal ultrasound (US) are not identical. The aim of this study was to investigate the differences between these classification systems with regard to levator defects on US and their clinical relevance for recurrence after prolapse surgery. METHODS: Women with previous cystocele repair underwent transperineal 3D US. Levator defects were graded according to the scoring system described with regard to MRI (DeLancey et al.) and perineal US (Dietz et al.). The results were compared using the weighted kappa and receiver operating characteristic (ROC) curves (SPSS version 20.0). RESULTS: We assessed 152 women. On US classification, more defects were categorized as highest grade compared with MRI classification [n = 64 (42 %) vs. n = 41 (28 %), p < 0.01]. The grades of levator defects on both scoring systems showed very good agreement, with a weighted kappa of 0.82 [95 % confidence interval (CI) 0.75-0.88). The predictive value of scoring systems for cystocele recurrence after prolapse surgery showed an area under the receiver operating curve (AUC) of 0.63 and 0.64, respectively. CONCLUSIONS: Comparison of the two scoring systems showed good agreement but was lowest for the highest-grade defects. There was no difference in predictive value between scoring systems for cystocele recurrence after prolapse surgery.

Pain relief and quality-of-life improvement after spinal cord stimulation in painful diabetic polyneuropathy: a pilot study.

BACKGROUND: Painful diabetic polyneuropathy (PDP) is associated with high pain scores and is difficult to treat. Therefore, spinal cord stimulation (SCS) has been suggested as second-line treatment. In this study, the feasibility and efficacy of SCS in PDP were investigated, as well as the predictive value of clinical sensory testing for the treatment outcome. METHODS: Fifteen patients with intractable PDP in the lower limbs were recruited. During lead implantation, the feasibility of achieving adequate paraesthesia coverage using one stimulation lead was investigated. If trial stimulation was successful, a definitive neurostimulator was implanted. Pain intensity was scored using an 11-point numeric rating scale and patients' global impression of change scale. Additionally, neuropathic pain characteristics, quality of life, sleep quality and mood were assessed. The predictive value of clinical sensory testing for the treatment outcome was analysed. RESULTS: Adequate paraesthesia coverage was achieved in 14 out of 15 patients. Clinically relevant pain relief was present in 11 patients after trial stimulation and 10 patients at 12 months. The quality of life was significantly increased at 2 weeks and 3 months in patients with successful SCS treatment. Several neuropathic pain characteristics and quality of sleep were improved at 2 weeks and 12 months. Preoperative clinical sensory testing did not differentiate between treatment responders from non-responders. CONCLUSIONS: SCS seems to be an efficacious and feasible treatment for intractable PDP. In this exploratory study, it was not possible to predict the treatment outcome using clinical sensory testing. These results justify performing a randomized clinical trial.

5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review.

Several pharmacological treatments are used to manage post-herpetic neuralgia (PHN). The use of topical analgesics, such as 5% lidocaine-medicated plaster (5% LMP), may be preferable to systemic treatments in that they are formulated to produce a local pain relieving effect with minimal systemic absorption. However, direct head-to-head comparisons are relatively few, and a rigorous assessment of the relative efficacy and safety of the various treatment options is lacking. The objective of this study was to compare 5% LMP for the relief of PHN with other relevant interventions and placebo. Six databases were searched up to May 2010. Quantitative methods for data synthesis were used, and a network meta-analysis was conducted. Twenty unique studies (32 publications) were included. Placebo-controlled studies showed 5% LMP to be effective in providing pain relief and reducing allodynia while adverse event rates were generally low. A comparison between 5% LMP and pregabalin indicated the non-inferiority of 5% LMP for pain reduction and showed greater improvement of quality of life for 5% LMP. Adverse events (AE) were significantly fewer with 5% LMP. In the network meta-analysis, only 5% LMP and gabapentin were associated with a greater change in pain from baseline than placebo [-15.50 (95% CI -18.85 to -12.16) and -7.56 (95% CI -12.52 to -2.59) respectively]. 5% LMP was shown to be more effective than capsaicin [-16.45 (95% CI -20.04 to -12.86)], gabapentin [-7.95 (95% CI -13.29 to -2.61)] and pregabalin [-13.45 (95% CI -19.19 to -7.71)]. For pain relief, two comparators were more effective than placebo [mean pain relief, gabapentin: 32.77 (95% CI 15.57-49.97); 5% LMP: 26.77 (95% CI 9.11-44.43)]. 5% LMP was shown to be comparable to gabapentin [-6.00 (95% CI -25.32-13.32)]. The results suggest that 5% LMP and gabapentin have similar effects on pain relief and that 5% LMP is more effective than capsaicin and pregabalin (change in pain from baseline). Topical agents, such as 5% LMP, are associated with fewer and less clinically significant AE than is the case for systemic agents. However, small numbers, and limited size and quality of included studies should be taken into account. Further studies are needed.

Diagnostic performance of breast technologists in reading mammograms in a clinical patient population.

PURPOSE: In the setting of an increasing workload for radiologists, this study focuses on the feasibility of skill mixing in breast imaging in a hospital radiology department. METHODS: Two radiological technologists with more than 10 years of experience in performing mammograms were trained in prereading mammograms to select the cases that require further evaluation by a radiologist. Mammograms of consecutive patients were independently evaluated by the technologists, next to the standard clinical interpretation by the radiologist on duty. Mammographic findings were recorded and a BI-RADS classification was assigned for each breast. Different prereading scenarios were analysed using clinical decision rules. Two different cut-off points of BI-RADS classifications were applied to the data. Analysis was performed for the overall clinical patient population as well as for a subgroup of patients with no immediate indication for further work-up. RESULTS: Mammograms of 1994 patients were evaluated. In total, 93 breast cancers were found in 91 patients (prevalence 4.6%). Sensitivity and specificity in selecting mammographic findings (cut-off point between BI-RADS 1 and BI-RADS 0, 2-5 and the radiologist's diagnosis as reference standard) was 98% and 74% for technologist 1 and 98% and 78% for technologist 2. In distinguishing normal and benign mammograms from those with abnormalities that are probably benign, suspicious or highly suggestive for malignancy (cut-off point BI-RADS 1-2 and BI-RADS 0, 3-5 and pathology results as reference standard), sensitivity decreased to 89% and 91% respectively. Specificity increased to 82% for both technologists. In a subgroup of 1389 patients with no immediate indication for additional imaging with the involvement of a radiologist, technologists obtained a mean sensitivity and specificity of 98% and 77% in detecting mammographic findings, and a mean sensitivity and specificity of 78% and 88% in detecting suspicious abnormalities. CONCLUSIONS: The employment of technologists in prereading mammograms seems to be an effective working strategy in daily clinical practice. However, its position in clinical practice remains indistinct as a continuous availability of radiologists still needs to be guaranteed. Nevertheless, as a substantial proportion of mammograms could be evaluated without the attention of a radiologist, the employment of technologists in prereading mammograms seems a promising new working strategy.

Screening strategies for tubal factor subfertility.

BACKGROUND: Different screening strategies exist to estimate the risk of tubal factor subfertility, preceding laparoscopy. Three screening strategies, comprising Chlamydia trachomatis IgG antibody testing (CAT), high-sensitivity C-reactive protein (hs-CRP) testing and hysterosalpingography (HSG), were explored using laparoscopy as reference standard and the occurrence of a spontaneous pregnancy as a surrogate marker for the absence of tubal pathology. METHODS: In this observational study, 642 subfertile women, who underwent tubal testing, participated. Data on serological testing, HSG, laparoscopy and interval conception were collected. Multiple imputations were used to compensate for missing data. RESULTS: Strategy A (HSG) has limited value in estimating the risk of tubal pathology. Strategy B (CAT-->HSG) shows that CAT significantly discerns patients with a high versus low risk of tubal pathology, whereas HSG following CAT has no additional value. Strategy C (CAT-->hs-CRP-->HSG) demonstrates that hs-CRP may be valuable in CAT-positive patients only and HSG has no additional value. CONCLUSIONS: CAT is proposed as first screening test for tubal factor subfertility. In CAT-negative women, HSG may be performed because of its high specificity and fertility-enhancing effect. In CAT-positive women, hs-CRP seems promising, whereas HSG has no additional value. The position and timing of laparoscopy deserves critical reappraisal.

Prospective evaluation of ischemia in brachial-basilic and forearm prosthetic arteriovenous fistulas for hemodialysis.

UNLABELLED: Ischemia is a devastating complication after arteriovenous fistula (AVF) creation. When not timely corrected, it may lead to amputation. Symptomatic ischemia occurs in 3.7-5% of the hemodialysis population. Upper arm AVFs have a higher incidence of ischemia compared to forearm AVFs. As more patients may need upper arm AVFs in the growing and older hemodialysis population, occurrence of symptomatic ischemia may increase. The purpose of this study is to identify predictors for occurrence of ischemia. METHODS: A prospective evaluation of ischemia was performed in patients randomised for either a brachial-basilic (BB-) AVF or a prosthetic forearm loop AVF. Clinical parameters, preoperative vessel diameters, access flows, digital blood pressures, digit-to-brachial indices (DBI) and interventions for ischemia were recorded. RESULTS: Sixty-one patients (BB-AVF 28) were studied. Seventeen patients (BB-AVF 8) developed ischemic symptoms. Six patients (BB-AVF 3) needed interventions for severe symptoms. Age, history of peripheral arterial reconstruction and radial artery volume flow were significant predictors for the occurrence of ischemia. CONCLUSION: Symptomatic ischemia occurred in 28% of patients with brachial-basilic and prosthetic forearm AVFs. Age, history of peripheral arterial reconstruction and radial artery volume flow might be important for prediction of ischemia.

The prevalence of postoperative pain in a sample of 1490 surgical inpatients.

BACKGROUND AND OBJECTIVE: To measure the prevalence of postoperative pain, an assessment was made of 1490 surgical inpatients who were receiving postoperative pain treatment according to an acute pain protocol. METHODS: Measurements of pain (scores from 0 to 100 on a visual analogue scale) were obtained three times a day on the day before surgery and on days 0-4 postoperatively; mean pain intensity scores were calculated. Patients were classified as having no pain (score 0-5), mild pain (score 6-40), moderate pain (score 41-74) or severe pain (score 75-100). RESULTS: Moderate or severe pain was reported by 41% of the patients on day 0, 30% on days 1 and 19%, 16% and 14% on days 2, 3 and 4. The prevalence of moderate or severe pain in the abdominal surgery group was high on postoperative days 0-1 (30-55%). A high prevalence of moderate or severe pain was found during the whole of days 1-4 in the extremity surgery group (20-71%) and in the back/spinal surgery group (30-64%). CONCLUSION: We conclude that despite an acute pain protocol, postoperative pain treatment was unsatisfactory, especially after intermediate and major surgical procedures on an extremity or on the spine.

[Pre-randomisation in study designs: getting past the taboo]. / Prerandomisatie bij wetenschappelijk onderzoek: een taboe doorbroken.

In October 2006 the Dutch Ministry of Health, Welfare and Sport announced that the use of pre-randomisation in study designs is admissible and not in conflict with the Dutch Medical Research in Human Subjects Act. With pre-randomisation, the conventional sequence of obtaining informed consent followed by randomisation is reversed. According to the original pre-randomisation design (Zelen design), participants are randomised before they are asked to consent; after randomisation, only participants in the experimental group are asked to consent to treatment and effect measurement. In the past, pre-randomisation has seldom been used, and when it was, it was often under the wrong circumstances. Awareness regarding the ethical, legal and methodological objections to pre-randomisation is increasing. About a decade ago, we illustrated the applicability and acceptability of pre-randomisation by means of a fictitious heroin provision trial. In general, pre-randomisation is justified if valid evaluation of the effects of an intervention is impossible using a conventional randomised design, e.g., if knowledge of the intervention may lead to non-compliance or drop-out in the control group, or when the intervention is an educational programme. Other requirements for pre-randomisation include the following: the study has a clinically relevant objective, it is likely that the study will lead to important new insights, the informed consent procedure bears no potential harm to participants, at least standard care is offered to participants in the control group, and the approval of an independent research ethics committee is obtained.

Contrast-enhanced magnetic resonance angiography findings prior to hemodialysis vascular access creation: a prospective analysis.

PURPOSE: To determine prospectively the clinical value of contrast-enhanced magnetic resonance angiography (CE-MRA) for assessment of the arterial inflow and venous outflow prior to vascular access (VA) creation. METHODS: Seventy-three patients underwent duplex ultrasonography (DUS) and CE-MRA prior to VA creation for detection of stenoses and occlusions. Two observers read the CE-MRA images for determination of inter-observer agreement. A VA was considered functional if it could be used for successful two-needle hemodialysis therapy within 2 months after creation. RESULTS: CE-MRA detected 6 stenosed, 8 occluded arterial vessel segments and 12 stenosed and 41 occluded venous vessel segments in 70 patients. Inter-observer agreement for detection of upper extremity arterial and venous stenoses and occlusions with CE-MRA was substantial to almost perfect (kappa values 0.76-0.96). CE-MRA detected lesions, not detected by DUS, that were associated with VA early failure and non-maturation in 33% of patients (7/21). Accessory veins detected preoperatively were the cause of VA non-maturation in a substantial group of patients (47%: 7/15). CONCLUSION: CE-MRA enables accurate detection of upper extremity arterial and venous stenosis and occlusions prior to VA creation. Preoperative CE-MRA identified arterial and venous stenoses, not detected by DUS that were associated with VA early failure and non-maturation. However, the use of gadolinium containing contrast media is currently contraindicated due the reported incidence of nephrogenic systemic fibrosis.

[Peripheral artery disease: clinical and cost comparison between duplex ultrasonography and contrast-enhanced magnetic resonance angiography--a multicenter randomized trial]. / De kosten en de effecten van magnetischeresonantieangiografie en duplexechografie bij patiënten met perifeer arterieel vaatlijden: een multicentrische gerandomiseerde studie.

OBJECTIVE: To determine the clinical and economic consequences of replacing duplex ultrasonography (DUS) by contrast-enhanced magnetic resonance angiography (CE-MRA) for the initial diagnostic work-up of patients with peripheral artery disease (PAD). DESIGN: Randomised multicentre study. METHOD: In the period from January 2002 to August 2003, consecutive patients with PAD were randomly assigned to CE-MRA or DUS. The primary outcome measure was the costs. Secondary outcome measures included the confidence with which the specialist could take a therapeutic decision on the basis of the imaging study, the change in disease severity, and the change in quality of life (QOL) assessed during 6 months of follow-up. In addition, all costs of imaging, therapeutic interventions and outpatient visits were calculated. RESULTS: After 6 months of follow-up the data on 352 patients were analysed. Use of CE-MRA reduced the number of additional vascular-imaging procedures by 42% ((69-40)/69) and the specialists felt more confident about their therapeutic decisions. The diagnostic costs of all imaging studies taken together were Euro 167,- higher, on average, in the CE-MRA group (p < 0.001). However, after 6 months of follow-up, no statistically significant differences were found between the two groups with regard to the change in disease severity, the QOL, or the total costs (p > 0.05). CONCLUSION: Based on these findings, a specialist that replaces DUS by CE-MRA will feel more confident about taking a therapeutic decision and will feel less need for additional imaging. However, the diagnostic costs were higher with CE-MRA.

Accessory veins and radial-cephalic arteriovenous fistula non-maturation: a prospective analysis using contrast-enhanced magnetic resonance angiography.

PURPOSE: To determine if large caliber accessory veins are associated with radial-cephalic arteriovenous fistula (RC-AVF) non-maturation. METHODS: RC-AVFs were created in 15 consecutive patients (radial artery and cephalic vein diameter > 2 mm, in the absence of arterial inflow or venous outflow stenoses or occlusions). Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed preoperatively for the determination of vessel diameters, stenoses and occlusions. The location and caliber of accessory veins was determined. Vascular access (VA) function was monitored and all interventions required to obtain a functioning VA were recorded. Non-maturation was defined as a nonfunctional VA at 2 months after creation. The predictive value of accessory vein caliber for prediction of RC-AVF non-maturation was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Non-maturation occurred in 10 (67%) out of 15 RC-AVFs. Large caliber accessory veins (n = 4), venous stenosis (n = 3) or both (n = 2) were associated with RC-AVF non-maturation. The presence of large caliber accessory veins was the only significant predictor for RC-AVF non-maturation (p = 0.01). Preoperatively detected accessory veins with a diameter > 70% of the cephalic vein diameter, had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 80, 100, 100 and 91% for prediction of RC-AVF non-maturation on patient level. Accessory vein ligation and dilatation of venous stenosis resulted in an overall salvage success rate of 89% (8/9). CONCLUSION: Large caliber accessory veins are associated with RC-AVF non-maturation. Ligation of large caliber accessory veins is a successful salvage procedure in a substantial group of patients. Furthermore, ligation of these accessory veins during initial RC-AVF creation can potentially reduce non-maturation rates; and therefore, preoperative assessment of accessory veins is recommended.

Effect of upper arm brachial basilic and prosthetic forearm arteriovenous fistula on left ventricular hypertrophy.

BACKGROUND: Creation of an arteriovenous fistula (AVF) may increase left ventricular hypertrophy in the hemodialysis population. Aim of this study was to compare the effects of a brachial-basilic (BB) AVF and the prosthetic brachial-antecubital forearm loop access (PTFE) on cardiac performance. METHODS: Patients were randomized to receive BB-AVF or prosthetic brachial-antecubital forearm loop access. Before and three months after AVF creation patients underwent an echocardiographic examination. Mann-Whitney U-test was used to compare relative increase between the measured cardiac parameters for the two groups. RESULTS: Twenty-seven patients participated in the study. The relative increase in left ventricular parameters was not significantly different between the two groups. Only left ventricular end-diastolic diameter tended to be of significance. Mean blood flow through the brachial artery was 1680+/-156 and 1450+/-221 mL/min three months after surgery for the PTFE and the BB-AVF group, respectively. CONCLUSION: After three months of follow-up, changes in cardiac structure were comparable between patients with BB and PTFE AVFs. Also access flow was comparable at this time. In general, the effects of creation of a fistula on LV structure were limited. Longer follow up time may be needed to explore the long term effects of different vascular accesses on cardiac function.

Accuracy, Precision, and Trending Ability of Electrical Cardiometry Cardiac Index versus Continuous Pulmonary Artery Thermodilution Method: A Prospective, Observational Study.

INTRODUCTION: Evaluation of accuracy, precision, and trending ability of cardiac index (CI) measurements using the Aesculon™ bioimpedance electrical cardiometry (Aesc) compared to the continuous pulmonary artery thermodilution catheter (PAC) technique before, during, and after cardiac surgery. METHODS: A prospective observational study with fifty patients with ASA 3-4. At six time points (T), measurements of CI simultaneously by continuous cardiac output pulmonary thermodilution and thoracic bioimpedance and standard hemodynamics were performed. Analysis was performed using Bland-Altman, four-quadrant plot, and polar plot methodology. RESULTS: CI obtained with pulmonary artery thermodilution and thoracic bioimpedance ranged from 1.00 to 6.75 L min-1 and 0.93 to 7.25 L min-1, respectively. Bland-Altman analysis showed a bias between CIBIO and CIPAC of 0.52 liters min-1 m-2, with LOA of [-2.2; 1.1] liters min-1 m-2. Percentage error between the two techniques was above 30% at every time point. Polar plot methodology and 4-quadrant analysis showed poor trending ability. Skin incision had no effect on the results. CONCLUSION: CI obtained by continuous PAC and CI obtained by Aesculon bioimpedance are not interchangeable in cardiac surgical patients. No effects of skin incision were found. International clinical trial registration number is ISRCTN26732484.

Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging.

BACKGROUND: One of the features of high-risk atherosclerotic plaques is a preponderance of macrophages. Experimental studies with hyperlipidemic rabbits have shown that ultrasmall superparamagnetic particles of iron oxide (USPIOs) accumulate in plaques with a high macrophage content and that this induces magnetic resonance (MR) signal changes. The purpose of our study was to investigate whether USPIO-enhanced MRI can also be used for in vivo detection of macrophages in human plaques. METHODS AND RESULTS: MRI was performed on 11 symptomatic patients scheduled for carotid endarterectomy before and 24 (n=11) and 72 (n=5) hours after administration of USPIOs (Sinerem) at a dose of 2.6 mg Fe/kg. Histological and electron microscopical analyses of the plaques showed USPIOs primarily in macrophages within the plaques in 10 of 11 patients. Histological analysis showed USPIOs in 27 of 36 (75%) of the ruptured and rupture-prone lesions and 1 of 14 (7%) of the stable lesions. Of the patients with USPIO uptake, signal changes in the post-USPIO MRI were observed by 2 observers in the vessel wall in 67 of 123 (54%) and 19 of 55 (35%) quadrants of the T2*-weighted MR images acquired after 24 and 72 hours, respectively. For those quadrants with changes, there was a significant signal decrease of 24% (95% CI, 33% to 15%) in regions of interest in the images acquired after 24 hours, whereas no significant signal change was found after 72 hours. CONCLUSIONS: Accumulation of USPIOs in macrophages in predominantly ruptured and rupture-prone human atherosclerotic lesions caused signal decreases in the in vivo MR images.

C-reactive protein, atherosclerosis and kidney function in hypertensive patients.

Previous studies have shown a relationship between coronary or carotid atherosclerosis and C-reactive protein (CRP) concentrations. In the present investigation, we evaluated the relationship between high-sensitivity CRP (hsCRP) concentrations and the presence of atherosclerotic lesions in the renal arteries and/or abdominal aorta. In 95 hypertensive patients who underwent intra-arterial DSA on suspicion of renovascular disease, blood was sampled during the procedure for measurement of hsCRP. The presence of atherosclerotic lesions was assessed at the level of the renal arteries and the abdominal aorta. Haemodynamically significant renal artery stenosis was diagnosed when 50% or more stenosis was observed. Patients with fibromuscular disease (n = 8) or incomplete data (n = 4) were excluded from analysis. The results revealed that the median hsCRP concentrations were significantly higher among the 57 patients with atherosclerosis of the aorta and/or renal arteries compared to those in the 26 patients without any angiographic lesions (4.6 vs 1.7 mg/l; P < 0.005). Moreover, in patients with renal artery stenosis, levels of hsCRP were higher when the degree of stenosis exceeded 50%. However, the association between hsCRP and the presence of atherosclerosis appeared to be confounded by serum creatinine, creatinine clearance, age and gender. In the whole group a significant inverse relationship was found between creatinine clearance and hsCRP (P < 0.05). In conclusion, hsCRP concentrations are related to atherosclerotic lesions in the renal arteries and the abdominal aorta. While this supports the view that atherosclerotic renal artery stenosis is part of a systemic inflammatory vascular disease, increased concentrations of CRP may also coincide with decreased renal function.