In 2017, the International Panel on Diagnosis of Multiple Sclerosis revised the McDonald 2010 criteria for the diagnosis of multiple sclerosis (MS). The new criteria are easier to apply and could ...lead to more and earlier diagnoses. It is important to validate these criteria globally for their accuracy in clinical practice.
To evaluate the diagnostic accuracy of the 2017 criteria vs the 2010 criteria in prediction of clinically definite MS in patients with a typical clinically isolated syndrome (CIS).
A total of 251 patients at Erasmus MC, Rotterdam, the Netherlands, in collaboration with several regional hospitals, fulfilled the inclusion criteria. Thirteen patients received another diagnosis early in the diagnostic process and therefore were excluded from the analyses. Nine patients with CIS declined to participate in the study. This left 229 patients who were included between March 2006 and August 2016 in this prospective CIS cohort. Patients underwent a baseline magnetic resonance imaging scan within 3 months after onset of symptoms and, if clinically required, a lumbar puncture was performed. Data were analyzed between December 2017 and January 2018.
Sensitivity, specificity, accuracy, and positive and negative predictive value were calculated after 1, 3, and 5 years for the 2017 vs the 2010 criteria.
Among the 229 patients with CIS, 167 were women (73%), and the mean (SD) age was 33.5 (8.2) years. One hundred thirteen patients (49%) were diagnosed as having CDMS during a mean (SD) follow-up time of 65.3 (30.9) months. Sensitivity for the 2017 criteria was higher than for the 2010 criteria (68%; 95% CI, 57%-77% vs 36%; 95% CI, 27%-47%; P < .001), but specificity was lower (61%; 95% CI, 50%-71% vs 85%; 95% CI, 76%-92%; P < .001). Using the 2017 criteria, more MS diagnoses could be made at baseline (n = 97 54%; 95% CI, 47%-61% vs n = 46 26%; 95% CI, 20%-32%; P < .001). In the group with at least 5 years of follow-up, 33% of patients who were diagnosed as having MS using the 2017 criteria did not experience a second attack during follow-up vs 23% when using the 2010 criteria.
The 2017 revised McDonald criteria are associated with greater sensitivity but less specificity for a second attack than the previous 2010 criteria. The tradeoff is that it leads to a higher number of MS diagnoses in patients with a less active disease course.
Background
The aim was to compare endovenous laser ablation (EVLA) and endovenous steam ablation (EVSA) for great saphenous varicose veins in a non‐inferiority study.
Methods
Patients with primary ...great saphenous vein reflux were randomized to EVLA (940 nm) or EVSA (SVS™). Primary outcomes were treatment success (vein obliteration) at 52 weeks, and Venous Clinical Severity Score (VCSS) at 12 weeks. Secondary outcomes were pain, satisfaction with treatment, duration of analgesia use and days lost from daily activities, changes in Aberdeen Varicose Vein Questionnaire (AVVQ) and EQ‐5D™ scores after 12 weeks, and complications at 2 and 12 weeks.
Results
A total of 227 legs were treated (EVSA, 117; EVLA, 110); 36 legs treated with EVSA received a low dose and the remaining 81 a higher dose. At 1 year, the treatment success rate after high‐dose EVSA was not inferior to that of EVLA: 92 (95 per cent confidence interval (c.i.) 86 to 98) versus 96 (92 to 100) per cent respectively. Changes in VCSS after 12 weeks were similar: −2·69 (95 per cent c.i. −2·34 to −3·04) and −2·51 (−2·10 to −2·93). AVVQ, EQ‐5D™ and EQ VAS scores improved equally 12 weeks after both treatments. Patients treated with EVSA reported less postprocedural pain, fewer days of analgesia use, were more satisfied with therapy, and had a shorter convalescence. Complication rates were comparable.
Conclusion
The 1‐year treatment success of high‐dose EVSA was not inferior to that of EVLA. Several secondary outcomes were in favour of EVSA. Registration number NCT02046967 (http://www.clinicaltrials.gov).
Steam as good as laser
Objectives
To report the variation in computed tomography perfusion (CTP) arterial input function (AIF) in a multicenter stroke study and to assess the impact this has on CTP results.
Methods
CTP ...datasets from 14 different centers were included from the DUtch acute STroke (DUST) study. The AIF was taken as a direct measure to characterize contrast bolus injection. Statistical analysis was applied to evaluate differences in amplitude, area under the curve (AUC), bolus arrival time (BAT), and time to peak (TTP). To assess the clinical relevance of differences in AIF, CTP acquisitions were simulated with a realistic anthropomorphic digital phantom. Perfusion parameters were extracted by CTP analysis using commercial software (IntelliSpace Portal (ISP), version 10.1) as well as an in-house method based on block-circulant singular value decomposition (bSVD).
Results
A total of 1422 CTP datasets were included, ranging from 6 to 322 included patients per center. The measured values of the parameters used to characterize the AIF differed significantly with approximate interquartile ranges of 200–750 HU for the amplitude, 2500–10,000 HU·s for the AUC, 0–17 s for the BAT, and 10–26 s for the TTP. Mean infarct volumes of the phantom were significantly different between centers for both methods of perfusion analysis.
Conclusions
Although guidelines for the acquisition protocol are often provided for centers participating in a multicenter study, contrast medium injection protocols still vary. The resulting volumetric differences in infarct core and penumbra may impact clinical decision making in stroke diagnosis.
Key Points
• The contrast medium injection protocol may be different between stroke centers participating in a harmonized multicenter study.
• The contrast medium injection protocol influences the results of X-ray computed tomography perfusion imaging.
• The contrast medium injection protocol can impact stroke diagnosis and patient selection for treatment.
Cancer treatments, toxicities and their effects on lifestyle, may impact levels of vitamin D. The aim of this study was to determine serum 25-hydroxyvitamin D3 (25(OH)D
3
) levels before, directly ...after and 6 months after chemotherapy in breast cancer patients (n = 95), and a comparison group of women (n = 52) not diagnosed with cancer. Changes in 25(OH)D
3
levels over time were compared using linear mixed models adjusted for age and season of blood sampling. Before start of chemotherapy, 25(OH)D
3
levels were lower in patients (estimated marginal mean 55.8 nmol/L, 95% confidence interval (95%CI) 51.2-60.4) compared to the comparison group (67.2 nmol/L, 95%CI 61.1-73.3, P = 0.003). Directly after chemotherapy, 25(OH)D
3
levels were slightly decreased (-5.1 nmol/L, 95%CI -10.7-0.5, P = 0.082), but ended up higher 6 months after chemotherapy (10.9 nmol/L, 95%CI 5.5-16.4, P < 0.001) compared to pre-chemotherapy values. In women without cancer, 25(OH)D
3
levels remained stable throughout the study. Use of dietary supplements did not explain recovery of 25(OH)D
3
levels after chemotherapy. We reported lower 25(OH)D
3
levels in breast cancer patients, which decreased during chemotherapy, but recovered to levels observed in women without cancer within 6 months after chemotherapy. Suboptimal 25(OH)D
3
levels in the majority of the participants highlight the relevance of monitoring in this vulnerable population.
Background
Several smartphone applications (app) with an automated risk assessment claim to be able to detect skin cancer at an early stage. Various studies that have evaluated these apps showed ...mainly poor performance. However, all studies were done in patients and lesions were mainly selected by a specialist.
Objectives
To investigate the performance of the automated risk assessment of an app by comparing its assessment to that of a dermatologist in lesions selected by the participants.
Methods
Participants of a National Skin Cancer Day were enrolled in a multicentre study. Skin lesions indicated by the participants were analysed by the automated risk assessment of the app prior to blinded rating by the dermatologist. The ratings of the automated risk assessment were compared to the assessment and diagnosis of the dermatologist. Due to the setting of the Skin Cancer Day, lesions were not verified by histopathology.
Results
We included 125 participants (199 lesions). The app was not able to analyse 90 cases (45%) of which nine BCC, four atypical naevi and one lentigo maligna. Thirty lesions (67%) with a high and 21 with a medium risk (70%) rating by the app were diagnosed as benign naevi or seborrhoeic keratoses. The interobserver agreement between the ratings of the automated risk assessment and the dermatologist was poor (weighted kappa = 0.02; 95% CI −0.08‐0.12; P = 0.74).
Conclusions
The rating of the automated risk assessment was poor. Further investigations about the diagnostic accuracy in real‐life situations are needed to provide consumers with reliable information about this healthcare application.
Purpose
The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2–3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the ...relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS.
Methods
We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan–Meier methods and Cox proportional hazards models were used for analyses.
Results
Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year osteopenia HR 0.82 (95% CI 0.45–1.49), osteoporosis HR 1.10 (95% CI 0.26–4.67) and the 3-year arm osteopenia HR 0.75 (95% CI 0.40–1.42), osteoporosis HR 1.86 (95% CI 0.43–8.01). Moreover, bisphosphonate use did not impact DRFS.
Conclusion
No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.
Aromatase inhibitors (AIs) are given as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women, also to those with chemotherapy-induced ovarian function failure. The ...current analysis reports on endocrine data of patients with chemotherapy-induced ovarian function failure who were included in the phase III DATA study assessing different durations of adjuvant anastrozole after tamoxifen.
We identified all patients with chemotherapy-induced ovarian function failure. Women who underwent a bilateral ovariectomy or used luteinizing hormone-releasing hormone agonists before random assignment were excluded. Plasma estradiol and follicle-stimulating hormone levels were monitored until 30 months after random assignment at local laboratories. We aimed to determine the ovarian function recovery (OFR) rate during AI use by the cumulative incidence competing risk method and analyzed the trend of estradiol levels during AI use by a nested case-control approach in which a subset of control subjects were compared with the OFR patients excluding the value at OFR diagnosis.
The 329 eligible patients had a median age of 50.0 years (range = 45-57 years) at random assignment. Thirty-nine patients developed OFR, corresponding with a 30-month recovery rate of 12.4%. Of these, 11 (28.2%) were age 50 years or older at AI initiation. The estradiol level decreased statistically significantly by 37.8% (95% CI = 27.4% to 46.7%) over the initial 30 months of AI treatment in both groups. However, the estradiol levels in the women who experienced OFR remained statistically significantly higher (difference = 20.6%, 95% CI = 2.0% to 42.7%) prior to OFR diagnosis compared with those who did not experience OFR.
The risk of OFR during AI treatment in breast cancer patients with chemotherapy-induced ovarian function failure is relevant, even beyond 45 years. Furthermore, women experiencing OFR had statistically significant higher estradiol levels during AI treatment (before OFR) than those without, with potential consequences regarding efficacy.
Abstract Aim Sentinel lymph node (SLN) biopsy is an accepted alternative to axillary lymph node dissection to assess the axillary tumour status in breast cancer patients. Memorial Sloan-Kettering ...Cancer Center (MSKCC) developed a nomogram to predict the likelihood of SLN metastases in breast cancer patients. Nomogram performance was tested on a Dutch population. Methods Data of 770 breast cancer patients who underwent successful SLN biopsy were collected. SLN metastases were present in 222 patients. A receiver operating characteristic (ROC) curve was drawn and the area under the curve was calculated to assess the discriminative ability of the MSKCC nomogram. A calibration plot was drawn to compare actual versus nomogram-predicted probabilities. Results The area under the ROC curve for the predictive nomogram was 0.67 (95% confidence interval 0.63–0.72) as compared to 0.75 in the original population. The nomogram was well-calibrated in the Dutch population. Conclusions In a Dutch population, the MSKCC nomogram estimated risk of sentinel node metastases in breast cancer patients well (i.e. calibration) with reasonable discrimination (area under ROC curve). Nomogram performance on core needle biopsy data has to be evaluated prospectively.
Abstract Purpose Severe fatigue after treatment of ductal carcinoma in situ (DCIS) has not been studied before. The current study examined (i) the prevalence of severe fatigue in DCIS patients versus ...breast cancer survivors (BCS) and healthy controls (HC), (ii) quality of life and functioning of severely versus non-severely fatigued DCIS patients and BCS, and (iii) the association of fatigue with psychosocial and behavioral factors in DCIS patients. Methods 89 patients treated for DCIS were matched on age and gender to 67 BCS and 178 HC (ratio 1:1:2). Fatigue was measured with the Fatigue Severity subscale of the Checklist Individual Strength. Results 23% of DCIS patients, 25% of BCS, and 6% of HC were severely fatigued (DCIS versus HC: p < 0.001). Severely fatigued DCIS patients had a lower quality of life and were more impaired in all domains of functioning than non-severely fatigued DCIS patients. Sleep problems, dysfunctional cognitions regarding fatigue, avoidance of activities, all-or-nothing behavior, perceived lack of social support, DCIS-related coping problems, and fear of future cancer occurrence were related to fatigue. Conclusions The prevalence of severe fatigue in DCIS patients was similar to BCS, but higher than in HC. Severely fatigued DCIS patients had a lower quality of life and more functional impairments. The psychosocial and behavioral fatigue-related factors in DCIS patients are known to perpetuate fatigue in BCS. These factors can be targeted in interventions for cancer-related fatigue. Our findings suggest that the same treatment elements might be applicable to severely fatigued DCIS patients.
Abstract Background Axillary pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is achieved in a substantial part of clinically node positive breast cancer patients. Treatment of ...the axilla after NAC varies widely, and new techniques to spare patients from an axillary lymph node dissection (ALND) are being introduced. Methods This Dutch nationwide survey regarding treatment of the initially clinically node positive axilla in patients receiving NAC was conducted amongst 148 surgical oncologists during November 2014 - June 2015, to survey the diagnostic work-up, axillary mapping and willingness to omit ALND. Results Axillary ultrasound was considered a standard procedure in the diagnostic work-up by 99% of participants. The majority of 70% of participants stated that ALND could possibly be omitted in node positive patients with a favourable response to NAC. A positive correlation was observed between the total amount of patients treated, versus patients receiving NAC (P<0.01). A total of 93 respondents performed axillary response evaluation after NAC, using imaging (72%), excision of localized lymph nodes (56%) or sentinel node biopsy (SNB; 45%). Decision-making in omitting ALND was influenced by the presence of N2-3 disease, patient age and type of breast surgery. Multivariable analysis showed that clinicians who administered NAC more often, were more likely to omit ALND (P<0.01). Discussion The majority of surgeons are inclined to omit ALND in case of an axillary pCR. A large variety of techniques are being used to identify a pCR. The lack of consensus on this topic indicates the need for guidelines based on the best available evidence.
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