Addition of FFRct in the diagnostic pathway of patients with stable chest pain to reduce unnecessary invasive coronary angiography (FUSION) : Rationale and design for the multicentre, randomised, controlled FUSION trial.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used in the diagnostic work-up of patients with stable chest pain. CCTA has an excellent negative predictive value, but a moderate positive predictive value for detecting coronary stenosis. Computed tomography-derived fractional flow reserve (FFRct) is a non-invasive, well-validated technique that provides functional assessment of coronary stenosis, improving the positive predictive value of CCTA. However, to determine the value of FFRct in routine clinical practice, a pragmatic randomised, controlled trial (RCT) is required. We will conduct an RCT to investigate the impact of adding FFRct analysis in the diagnostic pathway of patients with a coronary stenosis on CCTA on the rate of unnecessary invasive coronary angiography, cost-effectiveness, quality of life and clinical outcome. METHODS: The FUSION trial is a prospective, multicentre RCT that will randomise 528 patients with stable chest pain and anatomical stenosis of ≥ 50% but < 90% in at least one coronary artery of ≥ 2 mm on CCTA, to FFRct-guided care or usual care in a 1:1 ratio. Follow-up will be 1 year. The primary endpoint is the rate of unnecessary invasive coronary angiography within 90 days. CONCLUSION: The FUSION trial will evaluate the use of FFRct in stable chest pain patients from the Dutch perspective. The trial is funded by the Dutch National Health Care Institute as part of the research programme 'Potentially Promising Care' and the results will be used to assess if FFRct reimbursement should be included in the standard health care package.

Qualitative Evaluation of Common Quantitative Metrics for Clinical Acceptance of Automatic Segmentation: a Case Study on Heart Contouring from CT Images by Deep Learning Algorithms.

Organs-at-risk contouring is time consuming and labour intensive. Automation by deep learning algorithms would decrease the workload of radiotherapists and technicians considerably. However, the variety of metrics used for the evaluation of deep learning algorithms make the results of many papers difficult to interpret and compare. In this paper, a qualitative evaluation is done on five established metrics to assess whether their values correlate with clinical usability. A total of 377 CT volumes with heart delineations were randomly selected for training and evaluation. A deep learning algorithm was used to predict the contours of the heart. A total of 101 CT slices from the validation set with the predicted contours were shown to three experienced radiologists. They examined each slice independently whether they would accept or adjust the prediction and if there were (small) mistakes. For each slice, the scores of this qualitative evaluation were then compared with the Sørensen-Dice coefficient (DC), the Hausdorff distance (HD), pixel-wise accuracy, sensitivity and precision. The statistical analysis of the qualitative evaluation and metrics showed a significant correlation. Of the slices with a DC over 0.96 (N = 20) or a 95% HD under 5 voxels (N = 25), no slices were rejected by the readers. Contours with lower DC or higher HD were seen in both rejected and accepted contours. Qualitative evaluation shows that it is difficult to use common quantification metrics as indicator for use in clinic. We might need to change the reporting of quantitative metrics to better reflect clinical acceptance.

Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

Functional or not functional; that's the question: Can we predict the diagnosis functional movement disorder based on associated features?

BACKGROUND AND PURPOSE: Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. METHOD: Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independent t test for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. RESULTS: A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. DISCUSSION: Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study.

Symmetry of palatal shape during the first year of life in healthy infants.

OBJECTIVES: The purpose of this study was to quantify the symmetry of the alveolar process of the maxilla and palate during the first year of life in healthy infants with the help of a semiautomatic segmentation technique. MATERIALS AND METHODS: Maxillary plaster models of seventy healthy babies at 0, 3, 6, 9, and 12 months were collected and digitized. A semiautomatic segmentation tool was used to extract the alveolus and palate. The resulting model was aligned within a reference frame and mirrored on its medial plane. Distance maps were created and analyzed to compare and quantify the differences between the two hemispheres. Additional hemispherical width and area measurements were performed. An ANOVA test with additional post hoc tests was performed to check if the symmetry changed during development. Finally, the results were tested on intra- and interobserver variability. RESULTS: The absolute mean inter-surface distance between the original and mirrored models in each age group ranged between 0.23 and 0.30 mm. Width and area analysis showed a small but significant larger left palatal hemisphere. ANOVA and post hoc tests showed no significant difference in symmetry between groups. Reliability analysis showed no significant differences between observers. CONCLUSIONS: This study showed that in this infant population, only a small degree of palatal asymmetry was present, which can be considered as normal and clinically irrelevant. CLINICAL RELEVANCE: The data from this study can be used in future comparative studies as reference data. Furthermore, modeling of these data can help in predicting the growth pattern, which may lead to improved treatment protocols for children with craniofacial anomalies.

"Prophylactic" transanal irrigation (TAI) to prevent symptoms of low anterior resection syndrome (LARS) after rectal resection: results at 12-month follow-up of a controlled randomized multicenter trial.

BACKGROUND: Low anterior resection syndrome (LARS) is associated with a severe negative impact on patients' quality of life (QOL). In a recent prospective randomized controlled trial (RCT) by our group, early ("prophylactic") use of transanal irrigation (TAI) following rectal resection for rectal cancer was shown to improve symptoms associated with LARS significantly compared with a group under supportive therapy (ST) within 1 and 3 months following closure of the protective ileostomy. The aim of the present study was to evaluate the outcome after 12 months when patients had the option to choose between the two therapeutic options and/or modify the regimen of TAI (volume and time). METHODS: In the RCT, 18 patients had been allocated to start with TAI following ileostomy closure, while 19 patients remained on ST only. Once the 3-month follow-up had been completed patients could choose between TAI or ST, respectively, and were invited for follow-up after 12 months. The maximum number of bowel movements during the day and the Wexner and LARS score as well as physical (PC) and mental (MC) component of the SF-36 questionnaire were evaluated. Furthermore, in patients who had changed their treatment arm, reasons for this decision were reported. RESULTS: Six patients were lost to follow-up (all in the ST group). One patient from the ST group started with TAI due to problems associated with LARS, bringing the total number of TAI patients to 19. Nine patients from the previous TAI arm changed to ST due to the long duration of the emptying process (n: 8) or pain during TAI (n: 1), respectively. After 12 months, the median volume of water used for irrigation was 600 ml (range 200-1000 ml). The ten patients who continued with TAI patients showed a lower number of defecation episodes per daytime (TAI median 3; 1-6, ST median 5; 2-10, p: 0.018) and per night (TAI median 0; 0-1, ST median 1; 0-5, p: 0.004) compared to the ST group. Although the LARS score was lower in patients who used TAI after 12 months (TAI median 18; 9-32, ST median 30; 3-39), this failed to reach the level of significance (p: 0.063). Evaluation of the Wexner score and the 36-item Short Form Health Survey as well as comparison of patients who remained on TAI (n: 9) versus those who had stopped TAI after 3 months (n: 9) failed to find any statistically significant difference between TAI and ST. CONCLUSIONS: This follow-up study revealed that a considerable number of patients decided to stop TAI within 12 months. However, the number of bowel movements during the day were still lower when TAI was used than when patients had ST only. CATEGORY: Randomized trial. REGISTRATION NUMBER: DRKS00011752, https://apps.who.int/trialsearch/ .

[Activator or Herbst, what's best?] / Activator of Herbst; wat is beter?

In this article, the short- and long-term results of two types of functional appliances are discussed regarding their ability to stimulate the mandibular growth at mandibular retrognathia and reduce an increased overjet. Removable functional appliances, or activators, are compared to a fixed functional appliance, the Herbst appliance. The activator, often consisting of an acrylic base, is advised to be worn for 12 to 20 hours a day. The Herbst appliance consists of interconnected bands around the molar- and premolar bands, keeping the mandibula continuously positioned forward by means of hinges or telescopes. In the short-term, both appliances are effective in reducing the overjet, improving the molar-occlusion and reducing the mandibular retrognathia. The comparative literature is inconclusive as to which appliance is more effective on which level, skeletal or dentoalveolar. The removable appliances are more likely to be accepted at a younger age, whilst the fixed appliances are more suitable for the adolescents. The stability of the long-term treatment effects is minimally described in the existing literature. However, the highest stability rate seems to apply to the Herbst appliance. The impact of a widely applied second phase of treatment with fixed appliances, with possible use of intermaxillary class II elastics and retention using functional appliances is barely taken into account.

[Opinions on orthodontics: an online questionnaire among NTVT readers]. / Mening over orthodontie: een online enquête onder NTVT-lezers.

By means of an online questionnaire, the opinions of dental health practitioners on 'orthodontics' were assessed on the basis of 10 statements. There were 523 responses, 51% of which were from general practitioners, a relatively large number from orthodontists (31%) and 18% from other dental health practitioners. Concerning indication of treatment, dental health prior to treatment and the value of straightened teeth, opinions were clearly positive, somewhat more among orthodontist than among general practitioners. Patients knowledge concerning orthodontics and the negative side of orthodontics and their trust in the durability of orthodontic retention are all considered to be more positively present in patients by orthodontists than general practitioners. 1 in 3 non-orthodontists considered carrying out orthodontic procedures in the general practice to be fine. More than 90% of orthodontists disagreed. Female dental practitioners more often consider orthodontic treatment to belong with an orthodontist. The number of women was equally divided across the different groups.

Single layer graphene induces load-bearing molecular layering at the hexadecane-steel interface.

The influence of a single layer graphene on the interface between a polished steel surface and the model lubricant hexadecane is explored by high-resolution force microscopy. Nanometer-scale friction is reduced by a factor of three on graphene compared to the steel substrate, with an ordered layer of hexadecane adsorbed on the graphene. Graphene furthermore induces a molecular ordering in the confined lubricant with an average range of 4-5 layers and with a strongly increased load-bearing capacity compared to the lubricant on the bare steel substrate.

Three dimensional maxillary growth modeling in newborns.

OBJECTIVES: The aim of this study was to develop an accurate and intuitive semi-automatic segmentation technique to calculate an average maxillary arch and palatal growth profile for healthy newborns in their first year of life. MATERIALS AND METHODS: Seventy babies born between 1985 and 1988 were included in this study. Each child had five impressions made in the first year after birth that were digitalized. A semi-automatic segmentation tool was developed and used to assess the maxillary dimensions. Finally, random effect models were built to describe the growth and build a simulation population of 10,000 newborns. The segmentation was tested for inter- and intra-observer variability. RESULTS: The Pearson correlation coefficient for each of the variables was between 0.94 and 1.00, indicating high inter-observer agreement. The paired sample t test showed that, except for the tuberosity distance, there were small, but significant differences in the landmark placements between observers. Intra-observer repeatability was high, with Pearson correlation coefficients ranging from 0.87 to 1.00 for all measurements, and the mean differences were not significant. A third or second degree growth curve could be successfully made for each parameter. CONCLUSIONS: These findings indicated this method could be used for objective clinical evaluation of maxillary growth. CLINICAL RELEVANCE: The resulting growth models can be used for growth studies in healthy newborns and for growth and treatment outcome studies in children with cleft lip and palate or other craniofacial anomalies.

[Orthodontic treatment of a malocclusion with a compromised central upper incisor]. / Orthodontische behandeling van een malocclusie met een gecompromitteerde centrale bovenincisief.

An 11-year-old girl presented at an orthodontist asking for the correction of the crooked position of her upper and lower front teeth. In addition, the patient was concerned about the abnormal shape and size of tooth 21. There was a disto-occlusion, crowding and tooth gemination of tooth 21 with the shape of a dens invaginatus. The tooth, moreover, was infected. Teeth 21 and 14 were extracted as part of the treatment. By means of a guided transposition, tooth 23 was brought to the extraction site of tooth 21. Treatment was performed with hybrid fixed appliance techniques.

Direct Observation of Nonlinear Coupling between Pedestal Modes Leading to the Onset of Edge Localized Modes.

Prior to eruptive events such as edge localized modes (ELMs), quasicoherent fluctuations, referred to as pedestal modes, are observed in the edge of fusion devices. We report on the investigations of nonlinear coupling between these modes during quasistationary inter-ELM phases leading to the ELM onset. Three dominant modes, with density and magnetic signatures, are identified as key players in the triggering mechanism of certain classes of ELMs. We demonstrate that one of these modes is amplified by the two others through three wave interactions. The amplified mode is radially shifted relative to the other two modes towards the last-closed flux surface as the ELM event approaches. Our results suggest that nonlinear coupling of pedestal modes, associated with radial distortions pushing out of the pedestal, is a possible mechanism for the triggering of low frequency ELMs relevant for future fusion devices.

Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18F-FLT repeatability cohorts in solid tumors. 18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in 18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.

68Ga-PSMA 11 ligand PET imaging in patients with biochemical recurrence after radical prostatectomy - diagnostic performance and impact on therapeutic decision-making.

OBJECTIVE: To evaluate the diagnostic performance of [68Ga]Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA-PET) in the early detection of metastases in patients with biochemical recurrence (BCR) after radical prostatectomy (RP) for clinically non-metastatic prostate cancer, to compare it to CT/MRI alone and to assess its impact on further therapeutic decisions. MATERIAL AND METHODS: We retrospectively assessed 117 consecutive hormone-naïve BCR patients who had 68Ga-PSMA 11 PET/CT (n = 46) or PET/MRI (n = 71) between May 2014 and January 2017. BCR was defined as two PSA rises above 0.2 ng/ml. Two dedicated uro-oncological imaging experts (radiology/nuclear medicine) reviewed separately all images. All results were presented in a blinded sequential fashion to a multidisciplinary tumorboard in order to assess the influence of PSMA-PET imaging on decision-making. RESULTS: The median time from RP to BCR was 36 months (IQR 16-72). Overall, 69 (59%) patients received postoperative radiotherapy. Median PSA level at the time of imaging was 1.04 ng/ml (IQR 0.58-1.87). PSMA-positive lesions were detected in 100 (85.5%) patients. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-positive lesions could be confirmed by either histology (16%), PSA decrease in metastasis-directed radiotherapy (45%) or additional information in diffusion-weighted imaging when PET/MRI was performed (18%) in 79% of patients. PSMA-PET detected lesions in 67 patients (57.3%) who had no suspicious correlates according to the RECIST 1.1 criteria on MRI or CT. PSMA-PET changed therapeutic decisions in 74.6% of these 67 patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. CONCLUSIONS: We confirm the high performance of PSMA-PET imaging for the detection of disease recurrence sites in patients with BCR after RP, even at relatively low PSA levels. Moreover, it adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients.

Increase in the incidence of severe hypoglycaemia in people with Type 2 diabetes in spite of new drugs: analysis based on health insurance data from Germany.

AIM: To evaluate the use of new anti-hyperglycaemic agents that offer effective glycaemic control while reducing risk of hypoglycaemia, by analysing the incidence rates of severe hypoglycaemia in 2006 vs 2011 in relation to the medication. METHODS: This cross-sectional, population-based study used German health insurance data. All adults diagnosed with Type 2 diabetes mellitus (extrapolated to the German population: 6.35 million in 2006 and 7.52 million in 2011) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by their Anatomical Therapeutic Chemical code, and defined daily doses of each medication were calculated. RESULTS: The severe hypoglycaemic event rate was 460 per 100,000 people/year in 2006 and 490 per 100,000 people/year in 2011. In 2006 and 2011, 10.9% and 7.3%, respectively, of all people with severe hypoglycaemia were on sulfonylureas, while 12.7% and 9.3%, respectively, were on a combination therapy of metformin and sulfonylureas. Among those with severe hypoglycaemia, there were no prescriptions of dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists in 2006, but in 2011, 1.55% and 0.17%, of those with severe hypoglycaemia were receiving the respective treatments. In 2006 vs 2011, human insulin was prescribed for 11.3% vs 10.3% of people with severe hypoglycaemia, while insulin analogues were prescribed for 5.4% vs 8.1%, and mixed human insulins for 19.7% vs 14.0% of patients with severe hypoglycaemia. People receiving insulin analogue therapy had a higher risk of severe hypoglycaemia than those receiving metformin, after adjusting for age, gender, nephropathy diagnosis and year of survey (odds ratio 14.6; CI 13.3-15.9). CONCLUSION: The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, despite increased use of newer anti-hyperglycaemic agents and decreased use of insulins.

Hematopoiesis is prognostic for toxicity and survival of 223Radium treatment in patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival, hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin-levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis as well as adverse events during and after therapy were scored (grade 0-4) according to the CTCAE recommendations. The association of pre-therapeutic hematopoiesis, survival, HT and numbers of 223Ra cycles was analyzed. RESULTS: Median survival in all patients was 69.9 weeks; 77% of patients had pre-existing impaired Hb (1.7% grade 3, 12.5% grade 2, 62.5% grade 1). 8/56 (14.3%) had impaired Plt (grade 1) Maximum toxicity (Tox) grades of patients during treatment were grade 4 (Hb 1.7%; Plt 1.7%), grade 3 (Hb 14.3%; Plt 7.1%; Leu 7.1%), grade 2 (Hb 33.9%; Plt 7.1%; Leu 23.2%), grade 1 (Hb 46.4%; Plt 17.9%; Leu 23.2%) and grade 0 (Hb 5.4%; Plt 66.1%; Leu 44.6%). Interestingly, patients with thrombocytopenia had a significantly shorter survival compared to those with normal Plt levels (21 weeks vs not reached; P<0.003). As expected patients with pre-therapeutic low Hb-level (<10g/dL) had a significantly shorter survival compared to those with Hb-level >10g/dL (28 weeks vs not reached, P<0.004), whereas survival of patients with mildly impaired Hb (>10 but <13.5g/dL) did not differ from patients with normal levels of Hb (X vs. Y, P=...). Also patients with impaired Hb also developed significantly more grade 3 and 4 HT (Hb <10g/dL: 42.9 vs 14.3%, P<0.001; Plt <150G/mL: 25.0% vs 6.3%; P=0.002) and received significantly fewer treatment cycles (Hb<10g/dL: 5.1 vs 5.8, P<0.04; Plt <150G/mL: 3.4 vs 5.6; P<0.001). Neither extent of bone metastases nor previous chemotherapy were associated with survival, number of 223Ra cycles and HT. CONCLUSION: Patients with metastatic castration-resistant prostate cancer and impaired hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra therapy suffer from significantly more high-grade HT, shorter survival and receive significantly fewer 223Ra treatments. Therefore, Hb-levels and platelet counts are essential parameters for adequate patient selection for 223Ra therapy.

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

Observation of Critical-Gradient Behavior in Alfvén-Eigenmode-Induced Fast-Ion Transport.

Experiments in the DIII-D tokamak show that fast-ion transport suddenly becomes stiff above a critical threshold in the presence of many overlapping small-amplitude Alfvén eigenmodes (AEs). The threshold is phase-space dependent and occurs when particle orbits become stochastic due to resonances with AEs. Above threshold, equilibrium fast-ion density profiles are unchanged despite increased drive, and intermittent fast-ion losses are observed. Fast-ion Dα spectroscopy indicates radially localized transport of the copassing population at radii that correspond to the location of midcore AEs. The observation of stiff fast-ion transport suggests that reduced models can be used to effectively predict alpha profiles, beam ion profiles, and losses to aid in the design of optimized scenarios for future burning plasma devices.

Metabolic control and hypoglycaemia in people with type 2 diabetes on conventional or intensified insulin therapy: a 22 year retrospective single centre survey.

BACKGROUND: Multiple insulin injection therapy can easily be adapted to the patient's needs. Therefore, it is supposed that more intensive insulin therapy is associated with better metabolic control and less hypoglycaemia compared with a conventional insulin strategy in patients with type 2 diabetes. METHODS: HbA1c and incidence of non-severe and severe hypoglycaemia were analysed with regard to the strategy of insulin therapy [multiple insulin injection therapy with preprandial insulin with or without basal insulin or conventional insulin therapy with twice-daily premix insulin] from 20 943 visits of 1417 people treated with insulin with type 2 diabetes in a university outpatient department for endocrinology and metabolic diseases over a period of 22 years. RESULTS: Multiple insulin injection therapy was used in 13 896 (66.4%) of all 20 942 visits. Compared with conventional insulin therapy, these patients were younger (62.0 vs 68.7 years; p < 0.001), had a slightly longer diabetes duration (16.5 vs 15.8 years; p < 0.001) and higher body mass index (32.8 vs 30.9 kg/m(2) ; p < 0.001), a higher insulin dose (76.4 vs 46.5 IU/day; p < 0.001), more frequent blood glucose monitorings/week (24.2 vs 14.8; p < 0.001), a slightly lower HbA1c [7.7 (61.2) vs 7.9% (62.9 mmol/mol); p < 0.001] but more non-severe hypoglycaemic incidences per week (0.3 vs 0.2; p = 0.01). Episodes of severe hypoglycaemia were rare and comparable (0.01/patient/year) with both insulin therapy strategies. CONCLUSIONS: Multiple insulin injection therapy and conventional insulin therapy yielded comparable metabolic control with HbA1c below 8% (63.9 mmol/mol), but multiple insulin injection therapy is associated with higher body mass index and higher incidence of non-severe hypoglycaemia. Copyright © 2016 John Wiley & Sons, Ltd.

The Asher-McDade Aesthetic Index in Comparison With Two Scoring Systems in Nonsyndromic Complete Unilateral Cleft Lip and Palate Patients.

OBJECTIVE: To compare the Asher-McDade aesthetic index with 2 systems used to score the appearance of the nasolabial area in patients with a complete cleft lip and palate. DESIGN: Retrospective analysis of the results of complete unilateral cleft lip and palate patients. SETTING: Academic Center for Dentistry of Amsterdam and the VU University Medical Center. PATIENTS: Six-year-olds with complete unilateral cleft lip and palate. MAIN OUTCOME MEASURES: Cleft lip and palate patients assessed using the scoring system proposed by Prahl et al, a 5-point ordinal scale, and the scoring system proposed by Asher-McDade et al by 6 judges, 3 orthodontists, and 3 plastic surgeons. A calculation of intra- and interobserver reliability was made. A comparison was made of all the assessment methods using Kendalls' tau. RESULTS: Photographs of 55 children (38 boys and 17 girls) with complete unilateral cleft lip and palate were assessed. For the scoring system of Prahl et al, interobserver reliability varied from 0.43 to 0.53, for the 5-point scale between 0.45 and 0.57, and for the scoring system by Asher-McDade et al these varied between 0.52 and 0.66. Multiple significant correlations were found between the used scoring systems. CONCLUSION: It can be concluded that the Asher-McDade aesthetic index is still superior to the other scoring systems used in this study. However, all 3 scoring systems can reliably be used when 3 or more observers are used.