Neuropathological interpretation of stimulated Raman histology images of brain and spine tumors: part B

Intraoperative histopathological examinations are routinely performed to provide neurosurgeons with information about the entity of tumor tissue. Here, we quantified the neuropathological interpretability of stimulated Raman histology (SRH) acquired using a Raman laser imaging system in a routine clinical setting without any specialized training or prior experience. Stimulated Raman scattering microscopy was performed on 117 samples of pathological tissue from 73 cases of brain and spine tumor surgeries. A board-certified neuropathologist — novice in the interpretation of SRH — assessed image quality by scoring subjective tumor infiltration and stated a diagnosis based on the SRH images. The diagnostic accuracy was determined by comparison to frozen hematoxylin–eosin (H&E)-stained sections and the ground truth defined as the definitive neuropathological diagnosis. The overall SRH imaging quality was rated high with the detection of tumor cells classified as inconclusive in only 4.2% of all images. The accuracy of neuropathological diagnosis based on SRH images was 87.7% and was non-inferior to the current standard of fast frozen H&E-stained sections (87.3 vs. 88.9%, p = 0.783). We found a substantial diagnostic correlation between SRH-based neuropathological diagnosis and H&E-stained frozen sections (κ = 0.8). The interpretability of intraoperative SRH imaging was demonstrated to be equivalent to the current standard method of H&E-stained frozen sections. Further research using this label-free innovative alternative vs. conventional staining is required to determine to which extent SRH-based intraoperative decision-making can be streamlined in order to facilitate the advancement of surgical neurooncology.

The Impact of Lifedoc Health’s Multidisciplinary Team Approach on Cardiometabolic Risk Profile in a Multiracial Cohort of Adults with Obesity: A 1-year Exploratory Pilot Study

Background: Information regarding the effect of a multidisciplinary team (MDT) to improve cardiometabolic risk factors (CMRF) in routine clinical settings is lacking. Methods: In this one-year retrospective chart review (2018), 598 adults (African American 59%, Hispanic 35%, Caucasian 6%) with a mean age of 43.8 ± 14.0 were included. Qualifying patients (≥ 1 CMRF of overweight/obesity, prediabetes/diabetes, or hypertension) who were treated under an MDT protocol were compared to patients who qualified for MDT but were treated solely by a primary care provider (PCP). The MDT protocol included endocrinology-oriented visits, lifestyle counseling, care coordination, and shared medical appointments. Linear and binary regression were performed to identify the factors associated with CMRF changes. Results: Patients treated by MDT had a greater reduction (β, 95% CI) in weight (- 4.29 kg, -7.62, -0.97), BMI (-1.43 kg/m2, -2.68, -0.18), SBP (- 2.18 mmHg, -4.09, -0.26), and DBP (- 1.97 mmHg, -3.34, -0.60). They also had 77% higher odds of reducing ≥ 5% their initial weight, 83% higher odds of reducing 1 point of BMI, and 59% higher odds of reducing ≥2 mmHg DBP. No association was observed for MDT intervention and A1c changes. Conclusion: Compared to PCP, MDT-protocolized intervention improves CMRF in a multi-ethnic adult cohort in a routine clinical setting. Patient’s activation to access the best care and overcoming barriers from patients (weight perception, social determinants increasing no-shows to visits), providers (obesity stigma, clinical inertia), and health system (time constraints and high paperwork imposed by payers) is a priority.

PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature

<b><i>Introduction:</i></b> Programmed death-ligand 1 (PD-L1) expression is used for treatment prediction in non-small cell lung cancer (NSCLC). While cytology may be the only available material in the routine clinical setting, testing in clinical trials has mainly been based on biopsies. <b><i>Methods:</i></b> We included 2 retrospective cohorts of paired, concurrently sampled, cytological specimens and biopsies. Also, the literature on PD-L1 in paired cytological/histological samples was reviewed. Focus was on the cutoff levels ≥1 and ≥50% positive tumor cells. <b><i>Results:</i></b> Using a 3-tier scale, PD-L1 was concordant in 40/47 (85%) and 66/97 (68%) of the paired NSCLC cases in the 2 cohorts, with kappa 0.77 and 0.49, respectively. In the former cohort, all discordant cases had lower score in cytology. In both cohorts, concordance was lower in samples from different sites (e.g., biopsy from primary tumor and cytology from pleural effusion). Based on 25 published studies including about 1,700 paired cytology/histology cases, the median (range) concordance was 81–85% (62–100%) at cutoff 1% for a positive PD-L1 staining and 89% (67–100%) at cutoff 50%. <b><i>Conclusions:</i></b> The overall concordance of PD-L1 between cytology and biopsies is rather good but with significant variation between laboratories, which calls for local quality assurance.

A retrospective analysis of the therapeutic effects of 0.01% atropine on axial length growth in children in a real-life clinical setting

Background Several randomized controlled studies have demonstrated the beneficial effects of 0.01% atropine eye drops on myopia progression in children. However, treatment effects may be different in a routine clinical setting. We performed a retrospective analysis of our clinical data from children to investigate the effect of 0.01% atropine eye drops on myopia progression in a routine clinical setting. Methods Atropine-treated children were asked to instill one drop of 0.01% atropine in each eye every evening at 5 days a week. Myopic children who did not undergo atropine treatment served as controls. Objective refraction and ocular biometry of 80 atropine-treated and 103 untreated children at initial visit and 1 year later were retrospectively analyzed. Results Myopic refractions in the treated and untreated children at initial visit ranged from −0.625 to −15.25 D (−4.21 ± 2.90 D) and from −0.125 to −9.375 D (−2.92 ± 1.77 D), respectively. Ages at initial visit ranged from 3.2 to 15.5 years (10.1 ± 2.7 years) in the treated and from 3.4 to 15.5 years (11.2 ± 3.0 years) in untreated children. Two-factor ANOVA for age and atropine effects on axial length growth confirmed that axial length growth rates declined with age (p<0.0001) and revealed a significant inhibitory effect of atropine on axial length growth (p<0.0015). The atropine effect on axial length growth averaged to 0.08 mm (28%) inhibition per year. Effects on refraction were not statistically significant. Conclusion The observed atropine effects were not very distinctive: Statistical analysis confirmed that atropine reduced axial length growth, but to an extent of minor clinical relevance. It was also shown that beneficial effects of 0.01% atropine may not be obvious in each single case, which should be communicated with parents and resident ophthalmologists.

The usefulness of two CXCL13 assays on cerebrospinal fluid for the diagnosis of Lyme neuroborreliosis, a retrospective study in a routine clinical setting

Recent studies have shown elevated levels of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13) in the cerebrospinal fluid (CSF) of patients with early Lyme neuroborreliosis (LNB). In this retrospective study, we evaluated the diagnostic performance of the Quantikine CXCL13 ELISA (R&D Systems, Inc., MN, USA) and the recom Bead CXCL13 assay (Mikrogen, Neuried, Germany) for the detection of CXCL13 in CSF. All consecutive patients from whom a CSF and a serum sample had been collected between August 2013 and June 2016 were eligible for inclusion. Patients suspected of LNB were classified as definite, possible or non-LNB according to the guidelines of the European Federation of Neurological Societies (EFNS). Due to the limited number of LNB patients in the predefined study period, additional LNB patients were included from outside this period. In total, 156 patients (150 consecutive patients and six additional LNB patients) were included. Seven (4.5%) were classified as definite, eight (5.1%) as possible and 141 (90.4%) as non-LNB patients. Receiver operating characteristic (ROC) curve analysis comparing definite LNB patients with non-LNB patients showed a cut-off value of 85.9 pg/ml for the Quantikine CXCL13 ELISA and 252.2 pg/ml for the recom Bead CXCL13 assay. The corresponding sensitivities were 100% (95% confidence interval [CI]: 100%-100% (for both), the corresponding specificities were 98.6% [95% CI: 96.5%-100%] for the CXCL13 ELISA, and 97.2% [95% CI: 93.6%-100%] for the recom Bead CXCL13 assay, respectively. This study showed that CXCL13 in CSF can be of additional value for the diagnosis of LNB.

The Evolving Landscape of Chronic Lymphocytic Leukemia on Diagnosis, Prognosis and Treatment

The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients.

P410 Which patients with established Crohn’s disease benefit most from the use of the Patency capsule test prior to small bowel capsule endoscopy?

Background An important factor that limits a wider utilization of small bowel capsule endoscopy (SBCE) in Crohn’s Disease (CD) is the potential risk of retention. The Patency® capsule (PC) lowers the risk of SBCE retention by assessing pre-procedure intestinal patency. Our aims were to evaluate the use of PC in patients with established CD in routine clinical practice and to identify predictive factors of intestinal patency in CD patients. Methods We included all patients with CD followed in the Inflammatory Bowel Disease Unit of the Complejo Hospitalario de Navarra in which a SBCE was performed from 01/01/2008 to 31/12/2019. An intact PC excreted in its original shape within 30 hours after swallowing was considered a positive patency test. Results A total of 465 SBCE were indicated in 333 patients. In 61.9% a previous patency test with PC was performed, with significant differences in its use according to the age at diagnosis according to the Montreal classification (A1 75.9%, A2 64.8%, A3 46.1%) and behaviour (B2 81.3%, B3 80%, B1 54.2%), the indication (postoperative recurrence monitoring 87.2%, flare 65.5%, staging small bowel disease 52.4%, assessing mucosal healing 44.8%) and the presence of previous CD surgery (68.6% vs. 55.6%). In 33 cases (7%) SBCE was contraindicated due to negative patency test. Eleven SBCE were retained of the 432 procedures finally performed (incidence 2.5%; 95% CI 1.06%-4.02%). Retention occurred in 5.6% of procedures without prior PC compared to 0.4% with previous PC (p&lt;0.001). Stricturing disease (OR 2.94; 1.31-6.58), penetrating disease (OR 3.85; 1.59-9.31) and presence of elevated inflammatory markers (OR 3.73; 1.85-7.50) were identified as independent factors associated with retention (negative PC test or SBCE retention) in the multivariate analysis. Conclusion A patency test prior to SBCE was performed in 61.9% of patients with known CD. The use of PC is associated with a lower risk of SBCE retention in a routine clinical setting. Patients with stricturing or penetrating disease or elevation of inflammatory markers have significantly higher risk of retention and would therefore benefit from a pre-SBCE PC.

Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.MethodsPatients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).ResultsSixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was −0.02±0.13 logMAR (p=0.322). Significant reductions were recorded for FCP with a mean (±SD) change of −66.79±72.64 µm, −66.76±60.71 µm for CSRT and −0.27±0.24 mm³ for macular volume (all p<0.001). Intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis without occlusion.ConclusionsThe results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.

Quantitative comparison of data-driven gating and external hardware gating for 18F-FDG PET-MRI in patients with esophageal tumors

Background Respiratory motion during PET imaging reduces image quality. Data-driven gating (DDG) based on principal component analysis (PCA) can be used to identify respiratory signals. The use of DDG, without need for external devices, would greatly increase the feasibility of using respiratory gating in a routine clinical setting. The objective of this study was to evaluate data-driven gating in relation to external hardware gating and regular static image acquisition on PET-MRI data with respect to SUVmax and lesion volumes. Methods Sixteen patients with esophageal or gastroesophageal cancer (Siewert I and II) underwent a 6-min PET scan on a Signa PET-MRI system (GE Healthcare) 1.5–2 h after injection of 4 MBq/kg 18F-FDG. External hardware gating was done using a respiratory bellow device, and DDG was performed using MotionFree (GE Healthcare). The DDG raw data files and the external hardware-gating raw files were created on a Matlab-based toolbox from the whole 6-min scan LIST-file. For comparison, two 3-min static raw files were created for each patient. Images were reconstructed using TF-OSEM with resolution recovery with 2 iterations, 28 subsets, and 3-mm post filter. SUVmax and lesion volume were measured in all visible lesions, and noise level was measured in the liver. Paired t-test, linear regression, Pearson correlation, and Bland-Altman analysis were used to investigate difference, correlation, and agreement between the methods. Results A total number of 30 lesions were included in the study. No significant differences between DDG and external hardware-gating SUVmax or lesion volumes were found, but the noise level was significantly reduced in the DDG images. Both DDG and external hardware gating demonstrated significantly higher SUVmax (9.4% for DDG, 10.3% for external hardware gating) and smaller lesion volume (− 5.4% for DDG, − 6.6% for external gating) in comparison with non-gated static images. Conclusions Data-driven gating with MotionFree for PET-MRI performed similar to external device gating for esophageal lesions with respect to SUVmax and lesion volume. Both gating methods significantly increased the SUVmax and reduced the lesion volume in comparison with non-gated static acquisition. DDG resulted in reduced image noise compared to external device gating and static images.