Total Number Of Lesions Research Articles

An adaptive sparse Bayesian model combined with probabilistic label fusion for multiple sclerosis lesion segmentation in brain MRI

This paper presents a novel method for automatic segmentation of multiple sclerosis (MS) lesion in brain magnetic resonance (MR) image. The first research directly focuses on the development of an algorithm called the adaptive sparse Bayesian decision theorem (ASBDT), which integrates Markov random field theorem and Gibbs random field theorem to segment MS lesion in T1-w, T2-w and FLAIR images, respectively. The second research focus is based on a probabilistic label fusion (PLF) algorithm, which utilizes a set of prior known multi-atlas obtained from T1-w, T2-w and FLAIR images, respectively. The PLF algorithm is based on local weighted voting strategy, in which a specific coefficient obtained using the maximum likelihood function between the prior known atlas and the target image is assigned as the weight to individual atlas. The proposed segmentation approach is evaluated by 20 brain MR image data sets from the MICCAI MS Lesion Segmentation Challenge. The values of evaluation parameters TPR, PPV, DSC indicate that our approach is better than some other methods. According to the McDonald Criteria updated in 2017, the number and volume is a key point in defining the disease, we calculate the total MS lesion volume and number. Therefore, this novel approach has an added value for the clinical evaluation of MS lesion patients.

Intravascular ultrasound or optical coherence tomography-defined anatomic severity and hemodynamic severity assessed by coronary physiologic indices.

Fractional flow reserve or instantaneous wave-free ratio has become a standard criterion for revascularization. We sought to evaluate the association between intravascular ultrasound (IVUS) or optical coherence tomography (OCT)-derived quantitative plaque characteristics and the severity of physiologic stenosis. A total of 365 stenoses from 330 patients were evaluated. The association between IVUS or OCT-derived parameters and resting physiologic indices (instantaneous wave-free ratio, resting full-cycle ratio, and diastolic pressure ratio) and fractional flow reserve were explored. Among the total number of lesions, 50.7% and 58.1% showed an instantaneous wave-free ratio ≤ 0.89 and fractional flow reserve ≤ 0.80, respectively. IVUS or OCT-derived parameters showed significant correlations with resting physiologic indices (P values <.005). The best cutoff values of IVUS minimum lumen area (MLA), plaque burden, OCT-MLA, and OCT-area stenosis to predict functional significance were the same (IVUS-MLA: 3.4 mm2, plaque burden: 72.0%, OCT-MLA: 2.0 mm2, OCT-area stenosis: 68.0%) for all resting physiologic indices (instantaneous wave-free ratio, resting full-cycle ratio, and diastolic pressure ratio). The best cutoff values for fractional flow reserve were an IVUS-MLA of 3.8 mm2, plaque burden of 70.0%, OCT-MLA of 2.3 mm2, and OCT-area stenosis of 65.0%. Regardless of IVUS or OCT-derived parameters, the overall diagnostic accuracies of the parameters were lower than 70% and discrimination indices were less than 0.75 for resting physiologic indices or fractional flow reserve. The resting physiologic indices showed an identical relationship with IVUS or OCT-defined quantitative plaque characteristics. The diagnostic accuracy and discrimination ability of anatomical parameters were modest in predicting functional significance defined by resting and hyperemic invasive physiologic indices. This trial is registered at ClinicalTrials.gov (Identifier: NCT03795714).

Does a Delay in Anterior Cruciate Ligament Reconstruction Increase the Incidence of Secondary Pathology in the Knee? A Systematic Review and Meta-Analysis.

Previous systematic reviews looking at timing of anterior cruciate ligament reconstruction (ACLR) examined the functional outcomes and range of motion; however, few have quantified the effect of timing of surgery on secondary pathology. The goal of this study was to analyze the effects of early ACLRs versus delayed ACLR on the incidence of meniscal and chondral lesions. We searched MEDLINE, EMBASE, and CINAHL on March 20, 2018, for randomized control trials (RCTs) that compared early and delayed ACLR in a skeletally mature population. Two reviewers independently identified trials, extracted trial-level data, performed risk-of-bias assessments using the Cochrane Risk of Bias tool, and evaluated the study methodology using the Detsky scale. A meta-analysis was performed using a random-effects model with the primary outcome being the total number of meniscal and chondral lesions per group. Of 1887 citations identified from electronic and hand searches, we included 4 unique RCTs (303 patients). We considered early reconstruction as <3 weeks and delayed reconstruction as >4 weeks after injury. There was no evidence of a difference between early and late ACLR regarding the incidence of meniscal [relative risk (RR), 0.98; 95% confidence interval (CI), 0.74-1.29] or chondral lesions (RR, 0.88; 95% CI, 0.59-1.29), postoperative infection, graft rupture, functional outcomes, or range of motion. We found no evidence of benefit of early ACLR. Further studies may consider delaying surgery even further (eg, >3 months) to determine whether there are any real benefits to earlier reconstruction.

NIMG-04. MRI CHARACTERISTICS, TREATMENT APPROACH, PATTERN OF RELAPSE AND SURVIVAL FOR MULTICENTRIC GLIOBLASTOMA. A RETROSPECTIVE MONOCENTRIC STUDY

Abstract INTRODUCTION Multicentric glioblastoma (m-GBM) is a rare GBM variant (6–13% of all GBM cases). Published data is scarce and focus largely on enhancing foci. We performed a retrospective study to determine the incidence, imaging characteristics, treatment, pattern of relapse and prognosis of m-GBM. METHODS The neuropathological database of our institution was surveyed for histological diagnosis of adult GBM diagnosed between 01/01/2015 and 31/05/2018. All pre-operative MRI were reviewed to identify patients with m-GBM (defined as well separated enhancing and non-enhancing tumor foci). Medical records and follow-up MRI studies were reviewed to retrieve the data. RESULTS Of the 167 patients with newly diagnosed GBM, 14 (8%) presented with m-GBM. All of them had at least one enhancing lesion. The total number of lesions was 37 (19 enhancing and 18 non-enhancing) with a median number of lesions per patient of 2 (range 2 to 4). Median age at diagnosis was 66 (range: 49–79) years. MGMT status was known for 10 patients (5 methylated and 5 un-methylated). Nine patients underwent resection of the enhancing component whereas 5 patients had a biopsy. Median follow up was 14.3 (range: 2–30) months. All but one patient were treated by concurrent radiotherapy with temozolomide. All enhancing lesions were included in radiation field, whereas 4 of the 18 Flair lesions were not. Median progression free survival was 6.2 (range: 0–13.3) months. Six of the 18 non-enhancing tumor foci eventually displayed contrast enhancement during the follow-up. At last follow up, 12 patients died, with an overall survival of 12.3 months. Information regarding radiation fields, pattern of progression and molecular profile will be presented at the meeting. CONCLUSION m-GBM presents therapeutic dilemmas regarding the optimal therapeutical approach. Better understanding of the disease course and pattern of progression may help to optimize the therapeutic approach implying particularly to non-enhancing tumor foci.

Evoked potentials can predict future disability in people with clinically isolated syndrome.

The aim was to evaluate whether the addition of evoked potentials (EPs) which evaluate brainstem function to the EP score improves its ability to predict disease progression in people with clinically isolated syndrome (pwCIS). For 94 pwCIS, data on disease activity and progression after 2.9 (1.4-4.1) years of follow-up were available. Baseline characteristics included magnetic resonance imaging (MRI) parameters, visual EPs, auditory EPs, somatosensory EPs of the median and tibial nerves, vestibular evoked myogenic potentials and tongue somatosensory EPs. A multivariable regression model including age, sex, total number of T2 lesions on baseline MRI and EP score >13 showed that the total number of T2 lesions on baseline MRI and EP score >13 increase the likelihood for sustained accumulation of disability (SAD). After controlling for age, sex and the total number of T2 lesions on baseline MRI, the hazard of SAD for participants with EP score >13 is 4.093 times that of participants with EP score ≤13. EP score >13 also increases the likelihood for progression measured with a composite measure of progression which uses the Expanded Disability Status Scale, the nine-hole peg test and the timed 25-ft walk (exp(B)=5.577, 95% confidence interval1.520-20.468, P=0.01). The addition of EPs that evaluate brainstem function to the EP score enables prediction of the progression of disability in pwCIS.

5966Whole-vessel coronary 18F-sodium fluoride coronary microcalfication activity is associated with Low density plaque

Abstract Background 18F-sodium fluoride (18F-NaF) showed promise in imaging vulnerable coronary plaques. To date reporting of the highest per patient target to background ratio (TBR), total number of lesions with visual uptake and whole-heart tracer activity have been proposed. Unfortunately, each of these approaches has limitations which become especially prominent in patients with multiple foci of uptake, where reproducible global per-vessel measures are required. In oncology, the total metabolic active tumor volume has been found to be a significant prognostic factor for disease progression, recurrence and death. We evaluated if such methodology could be applied to coronary PET imaging. Purpose To quantify whole-vessel coronary 18F-NaF PET activity by utilizing automatically derived coronary vessel regions of interest (ROI) from CT angiography and assess the relationship between coronary microcalcification activity (CMA) and per vessel quantitative plaque characteristics on coronary CT angiography (CTA). Methods Twenty patients (68±6 years old, 70% males) with multivessel coronary artery disease underwent a 30 min single bed position PET 1h after a 250mB injection of 18F-NaF and CTA on a hybrid PET/CT scanner. We assessed coronary 18F-NaF uptake using novel whole-vessel tubular and tortuous 3D ROIs which were automatically extracted from CTA datasets. Within such ROIs we measured mean standard uptake value (SUV), maximum TBR (TBRmax) and the activity of voxels (CMA) above 1.25 the background SUV (left atrium activity). We used a previously established 1.25 TBRmax threshold to distinguish vessels positive and negative for 18F-NaF uptake. Coronary CTA datasets were analyzed by semi-automated software to quantify volumes and percentage lesion content of non-calcified plaque (NCP), low-density non-calcified plaque (LD-NCP, attenuation &lt;30 Hounsfield units) and calcified plaque (CP). Results 13 (65%) patients and 24 (40%) out of 60 main epicardial vessels presented with 18F-NaF uptake exceeding the 1.25 TBRmax threshold. While coronaries positive for uptake had higher CMA 0.92 [0.17, 2.03] vs 0.0, p&lt;0.001 and TBRmax 1.42 [1.35, 1.74] vs 1.09 [1.0, 1.19], there was no difference in whole-vessel SUVmean 0.90 [0.77, 1.17] vs 0.87 [0.78, 0.96], p=0.33 compared to 18F-NaF negative arteries. Of the quantitative plaque characteristics vessels positive for uptake had higher NCP 278.4 [145.6, 576.9] vs 184.6 [63.8, 367.0]mm3, p=0.030; and LD-NCP 8.4 [0.3, 11.0] vs 2.7 [12.1, 43.5]mm3, p=0.01. CMA showed a stronger correlation with LD-NCP (r=0.70, p&lt;0.001) than TBRmax (r=0.52, p&lt;0.001). On regression analysis LD-NCP acted as an independent predictor of CMA after adjustments for CP and vessel SUVmean (p&lt;0.001). Figure 1 Conclusions Whole-vessel 18F-NaF coronary microcalcification activity assessment with CT angiography automatically derived 3-dimensional ROIs is feasible and the measured coronary microcalcification burden correlates well with low density plaque. Acknowledgement/Funding This research was supported by grants R01HL135557 and R01HL133616 from the NHLBI/NIH and a grant from the Dr. Miriam &amp; Sheldon G. Adelson MRF

P14.72 Multicentric glioblastoma - A retrospective study of imaging characteristics, treatment approach, pattern of relapse and survival

Abstract BACKGROUND Multicentric glioblastoma (m-GBM), defined as well separated tumoral foci, is a rare GBM variant comprising 6–13% of all GBM cases. Published data regarding m-GBM is scarce and is largely reporting on multicentric enhancing foci. We performed a retrospective study to determine the incidence, imaging characteristics, treatment approach, pattern of relapse and prognosis of m-GBM. MATERIAL AND METHODS The neuropathological database of our institution was surveyed for histological diagnosis of adult GBM diagnosed between 01/01/2015 and 31/05/2018. All pre-operative MRI were reviewed to identify patients with m-GBM. We included in the definition of m-GBM well separated enhancing as well as non-enhancing tumor foci. The medical records and follow-up MRI studies were reviewed in order to retrieve the data. RESULTS Of the 170 patients with newly diagnosed GBM 14 (8%) presented with m-GBM. All of them had at least one enhancing lesion and 11 (78.5%) patients had additional well separated non-enhancing tumor foci. The total number of lesions was 37 (19 enhancing and 18 non-enhancing) with a median number of lesions per patient of 2 (range 2 to 4). Median age at diagnosis was 66 (range: 49–79) years. Nine of the patients (64%) underwent surgical resection of the enhancing component whereas 5 patients had only a biopsy. Median follow up was 14.3 (range: 2–30) months. All but one patients were treated by standard concurrent radiotherapy with temozolomide. Median progression free survival is 6.2 (range: 0–13.3) months. Five of the 18 non-enhancing tumor foci eventually displayed contrast enhancement during the course of the disease. At last follow up, 12 patients died, with an overall survival of 12.3 months. Information regarding radiation fields, pattern of disease progression and molecular profile will be presented at the meeting. CONCLUSION m-GBM presents therapeutic dilemas regarding the optimal surgical approach and radiation field planning. Better understanding of the disease course and pattern of progression may help to optimize the therapeutic approach implying particularly to non-enhancing tumor foci.

How Is Endoscopic Submucosal Dissection for Gastrointestinal Lesions Being Implemented? Results from an International Survey

Background and Study Aim: Superficial gastrointestinal (GI) neoplasms can be treated with endoscopic mucosal resection (EMR) and/or endoscopic submucosal dissection (ESD). These techniques are widely used in Eastern countries; however, its use in the West is limited. The aim of this study was to evaluate the current implementation of ESD in Western countries. Methods: Western endoscopists (n = 279) who published papers related to EMR/ESD between 2005 and 2017 were asked to complete an online survey from December 2017 to February 2018. Results: A total of 58 endoscopists (21%) completed the survey. Thirty performed ESD in the esophagus (52%), 45 in the stomach (78%), 36 in the co­lorectum (62%), and 6 in the duodenum (10%). The median total number of lesions ever treated per endoscopist was 190, with a median number per endoscopist in 2016 of 41 (7 [IQR 1–21], 6 [IQR 4–16], and 28 [5–63] in the esophagus, in the stomach, and in the colon and rectum, respectively). En bloc resection rates were 97% in the esophagus, 95% in the stomach, and 84% in the colorectum. Complete resection (R0) was achieved in 88, 91, and 81%, respectively. Curative rates were 69, 70, and 67%, respectively. Major complications (perforation or delayed bleeding) occurred more often in colorectal ESD (12 vs. 6% in the esophagus and 7% in the stomach). In the upper GI tract, the majority of resected lesions were intramucosal adenocarcinoma (59% in the esophagus; 47% in the stomach), while in the colorectum the majority were adenomas (59%). Conclusion: ESD seems to be performed by a large number of centers and endoscopists. Our results suggest that ESD is being successfully implemented in Western countries, achieving a good rate of efficacy and safety according to European guidelines.

MR Imaging Evaluation before Prophylactic Cranial Irradiation in Limited Stage Small Cell Lung Cancer: Prophylactic or Therapeutic?

Prophylactic cranial irradiation (PCI) has an established role in limited stage (LS) small cell lung cancer (SCLC) for reduction of brain metastasis (BM) incidence and prolongation of survival. However, in practice, a considerable number of patients were found to have BM at the time of PCI, even if no BM were revealed by brain magnetic resonance imaging (MRI) with contrast at diagnosis and no central nervous system (CNS) symptoms existed. This study aims to clarify the role of brain MRI evaluation before PCI in LS-SCLC. Retrospective review of LS-SCLC in our institute from January, 2013 to July, 2018 was conducted. The enrolled criteria included the followings: 1) response evaluation was complete remission (CR) or partial remission (PR) after 4-6 cycles of chemotherapy with platinum - based regimen and thoracic irradiation. PCI was performed within 3 months after systemic management; 2) BM was excluded by cranial MRI with contrast at diagnosis; 3) before PCI, contrast-enhanced cranial MRI was performed. 236 patients were enrolled. 142 (60.2%) were male. The mean age was 55.8 years old. 37 patients (15.7%) were revealed to have BM (total numbers of BM lesions: 154) at this stage by cranial MRI with contrast. Among this population of BM, 28 (75.7%) individuals had no any symptoms and the BM lesions in 37.8% patients were invisible by simulation CT scan. The mean largest diameter of the BM lesions was 10.7mm. 63.6% of the BM foci detected were ≤10mm. The mean interval from diagnosis of SCLC (initiation of first chemotherapy) to BM was 201 days (range: 148-251d), during which brain MRI with an average of 2.3 times was performed. In LS-SCLC, the occurrence of BM should be highly alert pre-PCI , even for those patients without CNS symptoms. For this special entity, BM lesions tend to be small and undetectable by CT scan. Contrast-enhanced cranial MRI is strongly recommended for decision making of PCI or BM radiotherapy.

Multimodal Clinical Imaging Assessment of the Outcome in Mild-to-Moderate Acne: A Prospective Study

Background: The quality of outcome assessment in acne studies has been either subjective/insufficient or time consuming through the ordinary lesion counting. Objective: To evaluate the application of multimodal clinical imaging (MCI), a combination of imaging technology and computation, in the assessment of acne lesions in a clinical study setting. Methods: A prospective, monocentric, single-group open study designed to evaluate the efficacy and tolerance of a cosmetic product (IP/SG) in subjects with mild-to-moderate facial acne by classical clinical counting (CCC) – change in the total/inflammatory/noninflammatory acne lesion number compared with baseline (D0) – Investigator Global Assessment (IGA) and self-reported outcomes. Concomitantly, MCI was administered. The study was performed for 12 weeks (D84) with a 4-week follow-up (D112). Results: Mean age of patients (n = 49) was 18.2 ± 3.7 years (range 13–25). The mean acne duration was 3.8 ± 2.8 years. The total number of lesions did not differ significantly between D0/D84 by both CCC and MCI. However, the Cardiff Acne Disability Index (CADI) and uncomfortable feeling improved at D28/D0, the perception of oily skin improved at D14/D0, and the perception of sticky skin improved from D28/D0 to D56/D0. Deterioration was detected between D84/D0 and D112/D0, namely after product discontinuation. Interestingly, a change in trend was recorded for acne lesions at D14/D0 by MCI but not by CCC. Conclusion: MCI, applied for the first time in a small clinical study setting, is at least as reliable as CCC and may allow for a sensitive longitudinal evaluation of single acne lesions and their response to products, especially in conditions where clinical evaluation reaches its limits.

Root caries on a Paranthropus robustus third molar from Drimolen.

Dental caries is often perceived as a modern human disease. However, their presence is documented in many early human groups, various nonhuman primates and, increasingly, our hominin ancestors and relatives. In this study, we describe an antemortem lesion on the root of a Paranthropus robustus third molar from Drimolen, South Africa, which likely represents another example of caries in fossil hominins. The molar, DNH 40, is dated to 2.0-1.5 Ma and displays a lesion on the mesial root surface, extending from the cementoenamel junction 3 mm down toward the apex. The position and severity of the lesion was macroscopically recorded and micro-CT scanned to determine the extent of dentine involvement. A differential diagnosis indicates root caries, as the lesion is indistinguishable from clinical examples. Although necrotic in appearance, external tertiary dentine is evident on a micro CT scan. Gingival recession and/or continuous eruption of the tooth as a result of extensive occlusal wear would have occurred to facilitate caries formation. Therefore, the lesion is likely linked to relative old age of this individual. This new example increases the total number of carious lesions described in P. robustus teeth to 10, on occlusal, interproximal, and now, root surfaces. Beyond the consumption of caries-causing food, caries formation would have also required the presence of requisite intraoral cariogenic bacteria in this individual and the species. Of interest, the presence of tertiary dentine on the outward surface suggests the DNH 40 lesion may have been arrested, that is, no longer active, perhaps relating to a change in diet or oral microbiome just prior to the individual's death.

Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension.

BackgroundCurrent data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing–remitting multiple sclerosis (RRMS) is limited.ObjectivesTo assess the efficacy of DMF in Japanese patients with RRMS.MethodsThe phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12–24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase.ResultsDMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12–24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks.ConclusionsDMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

ГЕМОЦИТИ ІНТАКТНОЇ ТА ІНВАЗОВАНОЇ ТРЕМАТОДАМИ ЖАБУРНИЦІ КИТАЙСЬКОЇ (MOLLUSCA, UNIONIDAE, ANODONTINAE)

The hemolymph of Sinanodonta woodiana (Lea, 1834) consists of plasma and cells of four types: prohemocytes (cambial cells), macronucleocytes, basophilic and eosinophilic granulocytes. The three latter cell types derive from the cambial cells though mitosis. The cellular sizes are: prohemocytes 14.3±0.4, basophilic granulocytes 20.9±0.7, young eosinophilic granulocytes 23.8±0.6, older eosinophilic granulocytes 25.7±0.1, macronucleocytes 26.1±0.3. All cells and their nuclei are roundish. Nuclear chromatin is either fine-grained fairly evenly distributed in the karyoplasm (in basophilic granulocytes), or more or less grouped dark-colored small (2-5-6) chromatin blocks. NC-ratio is maximum in macronucleocytes (0.6±0.01). NC-ratio of prohemocytes is 0.4±0.01, that of basophilic granulocytes is 0.3±0.01. NC-ratio of eosinophilic granulocytes is 0.2±0.01. Eosinophilic cells prevail in hemolymph elements: the young eosinophilic granulocytes make up 25.1±0.4 % and the older eosinophilic cells are up to 27.9±0.6 % of all hemocytes. The major functions of hemolymph cells are transport and protection.Transport is particularly pronounced in basophilic granulocytes in the form of phagocytosis. The protective function of hemocytes of different categories is manifested in a different way. Thus, some of the basophilic granulocytes develop into nephrocytes, which accumulate numerous (11-23) vacuoles of yellow-green-brown color. The vacuoles are subsequently excreted by the mollusk through the kidneys. The protective function of eosinophilic granulocytes is realized as false agglutination (these hemocytes clog into lumps that close wounds), which helps preventing blood loss. Also, eosinophilic granulocytes merge into multinucleated plasmodium, accumulating in large quantities around various foreign bodies (parasites or fragments of destroyed tissues) and encapsulating them to isolate from host tissues. At Northern Black Sea Coast, Chinese pond mussel is a common intermediate host of the trematode Rhipidocotyle companula Dujardin, 1845.The trematode inhabits the mollusk’s gonads. The parasitic sporocysts and cercariae were found in 29 % of examined mollusk specimens. Infestations were weak (up to 10 % of gonads were affected) in 22.4 % of infected mollusks, moderate (10 to 50 % of gonads) in 70 % of contaminated mollusks. Only 7.6 % of infected pond mussels were hyperinfected (100 % of gonads were affected).Weak trematode infestation is accompanied by localized damage. The total number and volume of parasitic focal lesions are generally insignificant. Moderate infection, and especially a hyperinfection cause not only the lesions in the hostal biotope, but also the overall pathological process in mollusk hosts. Simultaneously, the prohemocytes and basophilic granulocytes as well as their nuclei reduce in size. The total number of prohemocytes also declines by 1.7 times. The greatest decrease in the nuclear-cytoplasmic ratio (by a factor of 1.5-2) is noted also for prohemocytes and basophilic granulocytes. The vacuolization of karyoplasm and cytoplasm, the basophilization of cytoplasm, the degenerative changes in hemocyte nuclei (karyopicnosis, karyorexis, karyolysis), and the total number of aging and dying hemocytes are directly related to the level of infection intensity.

Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis

BackgroundBruton’s tyrosine kinase (BTK) regulates the functions of B cells and myeloid cells that are implicated in the pathogenesis of multiple sclerosis. Evobrutinib is a selective oral BTK inhibitor that has been shown to inhibit B-cell activation both in vitro and in vivo.MethodsIn this double-blind, randomized, phase 2 trial, we assigned patients with relapsing multiple sclerosis to one of five groups: placebo, evobrutinib (at a dose of 25 mg once daily, 75 mg once daily, or 75 mg twice daily), or open-label dimethyl fumarate (DMF) as a reference. The primary end point was the total (cumulative) number of gadolinium-enhancing lesions identified on T1-weighted magnetic resonance imaging at weeks 12, 16, 20, and 24. Key secondary end points included the annualized relapse rate and change from baseline in the score on the Expanded Disability Status Scale (EDSS).ResultsA total of 267 patients were randomly assigned to a trial group. The mean (±SD) total number of gadolinium-enhancing lesions during weeks 12 through 24 was 3.85±5.44 in the placebo group, 4.06±8.02 in the evobrutinib 25-mg group, 1.69±4.69 in the evobrutinib 75-mg once-daily group, 1.15±3.70 in the evobrutinib 75-mg twice-daily group, and 4.78±22.05 in the DMF group. The baseline adjusted rate ratios for the total number of lesions over time as compared with placebo were 1.45 in the evobrutinib 25-mg group (P=0.32), 0.30 in the evobrutinib 75-mg once-daily group (P=0.005), and 0.44 in the evobrutinib 75-mg twice-daily group (P=0.06). The unadjusted annualized relapse rate at week 24 was 0.37 in the placebo group, 0.57 in the evobrutinib 25-mg group, 0.13 in the evobrutinib 75-mg once-daily group, 0.08 in the evobrutinib 75-mg twice-daily group, and 0.20 in the DMF group. There was no significant effect of trial group on the change from baseline in the EDSS score. Elevations in liver aminotransferase values were observed with evobrutinib.ConclusionsPatients with relapsing multiple sclerosis who received 75 mg of evobrutinib once daily had significantly fewer enhancing lesions during weeks 12 through 24 than those who received placebo. There was no significant difference with placebo for either the 25-mg once-daily or 75-mg twice-daily dose of evobrutinib, nor in the annualized relapse rate or disability progression at any dose. Longer and larger trials are required to determine the effect and risks of evobrutinib in patients with multiple sclerosis. (Funded by EMD Serono; ClinicalTrials.gov number, NCT02975349.)

Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of multiple sclerosis.

As a high proportion of people with clinically isolated syndrome (pwCIS) exhibit sympathetic adrenergic and sudomotor dysfunction, the aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in pwCIS over a 2-year follow-up. This was a prospective cohort study in which 121 pwCIS were enrolled and followed for 2years. After 2-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and visit at month 24. Symptomatic dysautonomia was defined if the patient had a COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31>6.79) and CASS score >0. Complete CASS data at baseline and month 24 were available for 62 patients; in 24 (38.7%) patients there was worsening, in 16 (25.8%) there was improvement and in 22 (35.5%) there was no change in CASS score. In 90% of pwCIS (72 of 80) there was no change in parasympathetic nervous system tests, whereas 47.3% (35 of 74) had either worsening or improvement in sympathetic adrenergic and 28.6% (20 of 70) had either worsening or improvement in sudomotor function. A multivariable regression model identified the total number of T2 lesions as an independent predictor for worsening of symptomatic dysautonomia. No predictors for worsening or improving of CASS score were identified. A substantial proportion of pwCIS experienced worsening of ANS abnormalities during the 2-year follow-up and magnetic resonance imaging parameters seemed to predict these abnormalities.

Added Value of Contrast Medium in Whole-Body Hybrid Positron Emission Tomography/Magnetic Resonance Imaging: Comparison between Contrast-Enhanced and Non-Contrast-Enhanced Protocols

Objective: To compare the diagnostic ability and time efficiency of contrast-enhanced (CE) whole body fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) protocol and non-CE (NCE) protocol. Subjects and Methods: Ninety-three patients with known primary tumors underwent whole-body hybrid FDG PET/MRI during the follow-up of their malignancies with the use of NCE and CE protocols. The NCE PET/MRI protocol consisted of diffusion-weighted (b = 0 and 800 s/mm²) and T1-weighted Turbo Flash in the axial plane and T2-weighted HASTE sequence in the coronal planes (Σ = 25 min). The CE PET/MRI protocol was performed by acquiring axial serial CE 3D FS VIBE images in the upper abdomen, completing the whole body in the late phase in the axial plane (Σ = 30 min). Results: There was a statistically significant difference between the total number of lesions detected by the CE protocol (median 2, interquartile range (IQR) 0–14) and that detected by the NCE protocol (median 1, IQR 0–5; p < 0.001). More malignancies were detected in the abdomen (p < 0.001) and brain (p < 0.001) with the CE PET/MRI protocol, whereas no significant difference was present when comparing the 2 protocols in the detection of malignancies in the head and neck (p = 0.356), thorax (p = 0.09), lymph nodes (p = 0.196), and bone (p = 0.414). Conclusion: The CE FDG PET/MRI protocol enables fast and accurate detection of malignancies compared to the NCE FDG PET/MRI protocol, particularly in the upper abdomen and brain. Diagnostic ability and time efficiency can be increased with the proposed short CE protocol in place of the whole body PET/MRI protocol including both NCE and CE imaging sequences.

Diabetes Mellitus raise the Risk for Interval Colorectal Cancer and Advanced Colorectal Adenomas

Interval colorectal cancer (ICRC) means CRC discovered at or before the second colonoscopy during a screening interval. Literature provides data concerning the present issue, 7.2-9% of CRCs meeting the definition of interval CRC, without knowing the risk factors for this. We aimed to study if diabetes mellitus (DM) patients have a greater risk to develop ICRC/advanced adenomas (ACRA). We randomly included in the study 50 patients aged over 50 years old diagnosed with DM in whom colonoscopy was done for different reasons. Were excluded patients with CRC/ACRA diagnosed at first colonoscopy and results were compared to those of an age/gender-matched group of patients without DM as background. The interval of colonoscopies was fixed at 36 months (the shortest interval used for surveillance after a polypectomy). The total number of interval lesions significantly differs in our two groups (p=0.022, q=0.17). Interval CRC, serrated adenomas and villous adenomas were more frequent in the T2D group. (p = 0.013, p= 0.032, respectively p=0.011, q=0.14). DALM lesions were more frequently present in controls than in T2D (p=0.049) Results showed that patients with interval ICRC were two times more in DM group in male gender (p=0.003, ss) (4 pts, respectively 2 pts) and 1.5 times greater in female group (3 pts, respectively 2 pts). The rate of CRC occurrence during the interval period of 36 months was 0.16% for male and 0.12% for females. Regarding the occurrence of ACRA (villous/tubulovillous adenomas), male patients with DM had 3 times more ACRA lesions than the control group (p=0.029, ss) (9 pts vs 3 pts) while females patients with DM had 2 times more ACRA than controls (p=0.031, ss) (6 pts vs 3 pts). The rate of interval advanced CR lesions occurrence during the interval period of 36 months was 0.36% for male and 0.24% for females. DM looks be a risk factor ICRC/ACRA by accelerating the colorectal epithelial proliferation rate. Male gender looks to be more exposed to ICRC/ACRC, especially when they are diagnosed with metabolic co-morbidities like T2D.

P64-T Autonomic symptom burden can predict disease activity in early multiple sclerosis

Background We aimed to evaluate the role of autonomic nervous system (ANS) abnormalities on disease activity (relapses and new MRI lesions) and disease progression in people with clinically isolated syndrome (pwCIS). Methods Out of 121 consecutive pwCIS, data on disease activity and progression after 2.9 (1.4–4.1) years of follow-up was available for 94 pwCIS. Baseline characteristics included MRI parameters, Composite Autonomic System Score-31 (COMPASS-31), Composite Autonomic Scoring Scale and supine and standing levels of epinephrine and norepinephrine. Results Univariable logistic regression analysis revealed three predictors for occurrence of new relapse: COMPASS-31 > 7.32, total number of T2 lesions > 3 and decreasing supine level of epinephrine. The Kaplan-Meier survival analysis has shown that patients with COMPASS-31 > 7.32 have statistically significant lower probability that they will be relapse free (p = 0.013). It has also shown that the relative risk reduction for occurrence of new relapse in participants with COMPASS 7.32 and total number of T2 lesions >3 increase the likelihood and the increasing supine level of epinephrine reduces the likelihood of a relapse. Finally, results of the Cox regression analysis showed, that after controlling for age, sex, total number of T2 lesions > 3 and supine level of epinephrine, the hazard for occurrence of new relapse for participants with COMPASS-31 > 7.32 is 2.7 times that of participants with COMPASS-31 Conclusion This study provides evidence that ANS is an important contributor to development of disease activity in pwCIS.

P63-T Longitudinal assessment of autonomic nervous system in patients with first demyelinating event suggestive of MS

Background The aim of this study was to investigate the evolution of autonomic nervous system (ANS) abnormalities in people with clinically isolated syndrome (pwCIS) over a two-year follow-up. Material and methods This was a prospective cohort study in which 121 pwCIS were enrolled and followed for two years. After two-year follow-up, data were available for 84 pwCIS. ANS symptoms were evaluated with the Composite Autonomic System Score-31 (COMPASS-31) and results of the ANS tests were expressed using the Composite Autonomic Scoring Scale (CASS) at baseline and month 24 visits. Symptomatic dysautonomia was defined if the patient had COMPASS-31 value above the median of the whole cohort at baseline evaluation (COMPASS-31 > 6.79) and CASS score greater than 0. Results Complete CASS at baseline and M24 was available for 62 patients, in 24 (38.7%) patients there was worsening, in 16 (25.8%) improvement and in 22 (35.5%) there was no change in CASS. A multivariable regression model identified total number of T2 lesions as independent predictor for worsening of symptomatic dysautonomia. Although not reaching significance there was a trend of cervical spinal cord lesions as independent predictor for CASS worsening and age for CASS improvement (p = 0.058 and p = 0.051, respectively). Conclusion Substantial proportion of pwCIS experience worsening of ANS abnormalities during the two-year follow-up and MRI parameters seems to predict these abnormalities.

Antiacne and antiblotch activities of a formulated combination of Aloe barbadensis leaf powder, Garcinia mangostana peel extract, and Camellia sinensis leaf extract.

Objective: We compared the efficacy of an antiacne hydrogel formulated with a combination of Aloe barbadensis leaf extract, Garcinia mangostana peel extract, and Camellia sinensis leaf extract (AGC) at a ratio of 50:25:1 with a marketed 1% clindamycin gel (CG) formulation on antiacne and antiblotch activities.Methods: A single-center, parallel-arm, randomized controlled trial was performed from November 2017 to April 2018. Sixty subjects with mild–moderate acne severity according to the the American Academy of Dermatology were enrolled for the study. Outcome end points were total acne lesions (TALs) and acne-severity index (ASI) by counting the inflamed lesions and comedones and skin colors using erythema and melanin values.Results: For TALss, a decrease (P<0.0001) in the number of total inflamed lesions from baseline was evidenced in AGC group, but not in the CG group. Higher reduction in mean ASI in the AGC group was seen than in the CG group. However, there was no statistically significant difference regarding reduction in ASI between the AGC and CG groups. For erythema, a remarked reduction in skin redness from baseline was clearly seen at day 3 (P<0.05) in the AGC group. No significant decrease in erythema values from baseline was seen in the CG group. A significant decrease (P=0.037) in mean melanin value from baseline was seen in the AGC group after 14 days of twice-daily use, but not in the CG group. Both products were well tolerated, with no reports of severe adverse events.Conclusion: An anti-acne hydrogel containing a combination of mangosteen rinds, aloe vera gel, and green tea–leaf extracts was superior to 1% clindamycin gel in antiacne and antiblotch activities when measured by TALs and erythema and melanin values.