Grey Matter Atrophy and its Relationship with White Matter Lesions in Patients with Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease, Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder, and Multiple Sclerosis.

OBJECTIVE: To evaluate: (1) the distribution of gray matter (GM) atrophy in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and relapsing-remitting multiple sclerosis (RRMS); and (2) the relationship between GM volumes and white matter lesions in various brain regions within each disease. METHODS: A retrospective, multicenter analysis of magnetic resonance imaging data included patients with MOGAD/AQP4+NMOSD/RRMS in non-acute disease stage. Voxel-wise analyses and general linear models were used to evaluate the relevance of regional GM atrophy. For significant results (p < 0.05), volumes of atrophic areas are reported. RESULTS: We studied 135 MOGAD patients, 135 AQP4+NMOSD, 175 RRMS, and 144 healthy controls (HC). Compared with HC, MOGAD showed lower GM volumes in the temporal lobes, deep GM, insula, and cingulate cortex (75.79 cm3); AQP4+NMOSD in the occipital cortex (32.83 cm3); and RRMS diffusely in the GM (260.61 cm3). MOGAD showed more pronounced temporal cortex atrophy than RRMS (6.71 cm3), whereas AQP4+NMOSD displayed greater occipital cortex atrophy than RRMS (19.82 cm3). RRMS demonstrated more pronounced deep GM atrophy in comparison with MOGAD (27.90 cm3) and AQP4+NMOSD (47.04 cm3). In MOGAD, higher periventricular and cortical/juxtacortical lesions were linked to reduced temporal cortex, deep GM, and insula volumes. In RRMS, the diffuse GM atrophy was associated with lesions in all locations. AQP4+NMOSD showed no lesion/GM volume correlation. INTERPRETATION: GM atrophy is more widespread in RRMS compared with the other two conditions. MOGAD primarily affects the temporal cortex, whereas AQP4+NMOSD mainly involves the occipital cortex. In MOGAD and RRMS, lesion-related tract degeneration is associated with atrophy, but this link is absent in AQP4+NMOSD. ANN NEUROL 2024;96:276-288.

Prognostic value of single-subject grey matter networks in early multiple sclerosis.

The identification of prognostic markers in early multiple sclerosis (MS) is challenging and requires reliable measures that robustly predict future disease trajectories. Ideally, such measures should make inferences at the individual level to inform clinical decisions. This study investigated the prognostic value of longitudinal structural networks to predict 5-year Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting MS (RRMS). We hypothesized that network measures, derived from MRI, outperform conventional MRI measurements at identifying patients at risk of developing disability progression. This longitudinal, multicentre study within the Magnetic Resonance Imaging in MS (MAGNIMS) network included 406 patients with RRMS (mean age = 35.7 ± 9.1 years) followed up for 5 years (mean follow-up = 5.0 ± 0.6 years). EDSS was determined to track disability accumulation. A group of 153 healthy subjects (mean age = 35.0 ± 10.1 years) with longitudinal MRI served as controls. All subjects underwent MRI at baseline and again 1 year after baseline. Grey matter atrophy over 1 year and white matter lesion load were determined. A single-subject brain network was reconstructed from T1-weighted scans based on grey matter atrophy measures derived from a statistical parameter mapping-based segmentation pipeline. Key topological measures, including network degree, global efficiency and transitivity, were calculated at single-subject level to quantify network properties related to EDSS progression. Areas under receiver operator characteristic (ROC) curves were constructed for grey matter atrophy and white matter lesion load, and the network measures and comparisons between ROC curves were conducted. The applied network analyses differentiated patients with RRMS who experience EDSS progression over 5 years through lower values for network degree [H(2) = 30.0, P < 0.001] and global efficiency [H(2) = 31.3, P < 0.001] from healthy controls but also from patients without progression. For transitivity, the comparisons showed no difference between the groups [H(2) = 1.5, P = 0.474]. Most notably, changes in network degree and global efficiency were detected independent of disease activity in the first year. The described network reorganization in patients experiencing EDSS progression was evident in the absence of grey matter atrophy. Network degree and global efficiency measurements demonstrated superiority of network measures in the ROC analyses over grey matter atrophy and white matter lesion load in predicting EDSS worsening (all P-values < 0.05). Our findings provide evidence that grey matter network reorganization over 1 year discloses relevant information about subsequent clinical worsening in RRMS. Early grey matter restructuring towards lower network efficiency predicts disability accumulation and outperforms conventional MRI predictors.

Diagnostic Performance of Cortical Lesions and the Central Vein Sign in Multiple Sclerosis.

Importance: Multiple sclerosis (MS) misdiagnosis remains an important issue in clinical practice. Objective: To quantify the performance of cortical lesions (CLs) and central vein sign (CVS) in distinguishing MS from other conditions showing brain lesions on magnetic resonance imaging (MRI). Design, Setting, and Participants: This was a retrospective, cross-sectional multicenter study, with clinical and MRI data acquired between January 2010 and May 2020. Centralized MRI analysis was conducted between July 2020 and December 2022 by 2 raters blinded to participants' diagnosis. Participants were recruited from 14 European centers and from a multicenter pan-European cohort. Eligible participants had a diagnosis of MS, clinically isolated syndrome (CIS), or non-MS conditions; availability of a brain 3-T MRI scan with at least 1 sequence suitable for CL and CVS assessment; presence of T2-hyperintense white matter lesions (WMLs). A total of 1051 individuals were included with either MS/CIS (n = 599; 386 [64.4%] female; mean [SD] age, 41.5 [12.3] years) or non-MS conditions (including other neuroinflammatory disorders, cerebrovascular disease, migraine, and incidental WMLs in healthy control individuals; n = 452; 302 [66.8%] female; mean [SD] age, 49.2 [14.5] years). Five individuals were excluded due to missing clinical or demographic information (n = 3) or unclear diagnosis (n = 2). Exposures: MS/CIS vs non-MS conditions. Main Outcomes and Measures: Area under the receiver operating characteristic curves (AUCs) were used to explore the diagnostic performance of CLs and the CVS in isolation and in combination; sensitivity, specificity, and accuracy were calculated for various cutoffs. The diagnostic importance of CLs and CVS compared to conventional MRI features (ie, presence of infratentorial, periventricular, and juxtacortical WMLs) was ranked with a random forest model. Results: The presence of CLs and the previously proposed 40% CVS rule had a sensitivity, specificity, and accuracy for MS of 59.0% (95% CI, 55.1-62.8), 93.6% (95% CI, 91.4-95.6), and 73.9% (95% CI, 71.6-76.3) and 78.7% (95% CI, 75.5-82.0), 86.0% (95% CI, 82.1-89.5), and 81.5% (95% CI, 78.9-83.7), respectively. The diagnostic performance of the CVS (AUC, 0.89 [95% CI, 0.86-0.91]) was superior to that of CLs (AUC, 0.77 [95% CI, 0.75-0.80]; P < .001), and was increased when combining the 2 imaging markers (AUC, 0.92 [95% CI, 0.90-0.94]; P = .04); in the random forest model, both CVS and CLs outperformed the presence of infratentorial, periventricular, and juxtacortical WMLs in supporting MS differential diagnosis. Conclusions and Relevance: The findings in this study suggest that CVS and CLs may be valuable tools to increase the accuracy of MS diagnosis.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer.

Endometriosis-associated ovarian cancer (EOC) consisting of endometrioid cancer and clear-cell ovarian cancer could be promoted by many factors. miRNAs, which are small, non-coding molecules of RNA, are among them. The aim of this study was to detect miRNAs connected with the malignant transformation of endometriosis. FFPE (formalin-fixed, paraffin-embedded) samples of 135 patients operated on for endometriosis and different types of ovarian cancer (EOC and HGSOC-high-grade serous ovarian cancer) were studied. Healthy ovarian tissue was used as a control group. From the expression panel of 754 miRNAs, 7 were chosen for further tests according to their ROC (receiver operating characteristic) curves: miR-1-3p, miR-125b-1-3p, miR-31-3p, miR-200b-3p, miR-502-5p, miR-503-5p and miR-548d-5p. Furthermore, other potentially important clinical data were analysed, which included age, BMI, Ca-125 concentration, miscarriages and deliveries and concomitant diseases such as hypertension, type 2 diabetes and smoking. Among the miRNAs, miR200b-3p had the lowest expression in neoplastic tissues. miR31-3p had the highest expression in women without any lesions in the ovaries. miR-502-5p and miR-548-5p did not differ between the studied groups. The examined miRNA panel generally distinguished significantly normal ovarian tissue and endometriosis, normal ovarian tissue and cancer, and endometriosis and cancer. The malignant transformation of endometriosis is dependent on different factors. miRNA changes are among them. The studied miRNA panel described well the differences between endometriosis and EOC but had no potential to differentiate types of ovarian cancer according to their origin. Therefore, examination of a broader miRNA panel is needed and might prove itself advantageous in clinical practice.

Task-based functional connectivity reveals aberrance with the salience network during emotional interference in late-life depression.

OBJECTIVES: Late-life depression (LLD) is a common and debilitating disorder. Previously, resting-state studies have revealed abnormal functional connectivity (FC) of brain networks in LLD. Since LLD is associated with emotional-cognitive control deficits, the aim of this study was to compare FC of large-scale brain networks in older adults with and without a history of LLD during a cognitive control task with emotional stimuli. METHODS: Cross-sectional case-control study. Twenty participants diagnosed with LLD and 37 never-depressed adults 60-88 years of age underwent functional magnetic resonance imaging during an emotional Stroop task. Network-region-to-region FC was assessed with seed regions in the default mode, the frontoparietal, the dorsal attention, and the salience networks. RESULTS: FC between salience and sensorimotor network regions and between salience and dorsal attention network regions were reduced in LLD patients compared to controls during the processing of incongruent emotional stimuli. The normally positive FC between these networks were negative in LLD patients and inversely correlated with vascular risk and white matter hyperintensities. CONCLUSIONS: Emotional-cognitive control in LLD is associated with aberrant functional coupling between salience and other networks. This expands on the network-based LLD model and proposes the salience network as a target for future interventions.

Clinical and MRI measures to identify non-acute MOG-antibody disease in adults.

MRI and clinical features of myelin oligodendrocyte glycoprotein (MOG)-antibody disease may overlap with those of other inflammatory demyelinating conditions posing diagnostic challenges, especially in non-acute phases and when serologic testing for MOG antibodies is unavailable or shows uncertain results. We aimed to identify MRI and clinical markers that differentiate non-acute MOG-antibody disease from aquaporin 4 (AQP4)-antibody neuromyelitis optica spectrum disorder and relapsing remitting multiple sclerosis, guiding in the identification of patients with MOG-antibody disease in clinical practice. In this cross-sectional retrospective study, data from 16 MAGNIMS centres were included. Data collection and analyses were conducted from 2019 to 2021. Inclusion criteria were: diagnosis of MOG-antibody disease; AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis; brain and cord MRI at least 6 months from relapse; and Expanded Disability Status Scale (EDSS) score on the day of MRI. Brain white matter T2 lesions, T1-hypointense lesions, cortical and cord lesions were identified. Random forest models were constructed to classify patients as MOG-antibody disease/AQP4-neuromyelitis optica spectrum disorder/multiple sclerosis; a leave one out cross-validation procedure assessed the performance of the models. Based on the best discriminators between diseases, we proposed a guide to target investigations for MOG-antibody disease. One hundred and sixty-two patients with MOG-antibody disease [99 females, mean age: 41 (±14) years, median EDSS: 2 (0-7.5)], 162 with AQP4-neuromyelitis optica spectrum disorder [132 females, mean age: 51 (±14) years, median EDSS: 3.5 (0-8)], 189 with multiple sclerosis (132 females, mean age: 40 (±10) years, median EDSS: 2 (0-8)] and 152 healthy controls (91 females) were studied. In young patients (<34 years), with low disability (EDSS < 3), the absence of Dawson's fingers, temporal lobe lesions and longitudinally extensive lesions in the cervical cord pointed towards a diagnosis of MOG-antibody disease instead of the other two diseases (accuracy: 76%, sensitivity: 81%, specificity: 84%, P < 0.001). In these non-acute patients, the number of brain lesions < 6 predicted MOG-antibody disease versus multiple sclerosis (accuracy: 83%, sensitivity: 82%, specificity: 83%, P < 0.001). An EDSS < 3 and the absence of longitudinally extensive lesions in the cervical cord predicted MOG-antibody disease versus AQP4-neuromyelitis optica spectrum disorder (accuracy: 76%, sensitivity: 89%, specificity: 62%, P < 0.001). A workflow with sequential tests and supporting features is proposed to guide better identification of patients with MOG-antibody disease. Adult patients with non-acute MOG-antibody disease showed distinctive clinical and MRI features when compared to AQP4-neuromyelitis optica spectrum disorder and multiple sclerosis. A careful inspection of the morphology of brain and cord lesions together with clinical information can guide further analyses towards the diagnosis of MOG-antibody disease in clinical practice.

Brain disconnectome mapping derived from white matter lesions and serum neurofilament light levels in multiple sclerosis: A longitudinal multicenter study.

BACKGROUND AND OBJECTIVES: Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage in patients with multiple sclerosis (MS) than conventional lesion characteristics. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative imaging-based brain network aberrations and levels of serum neurofilament light chain (NfL) as a neuroaxonal injury biomarker. METHODS: MS patients (n = 312, mean age 42.9 years, 71 % female) and healthy controls (HC) (n = 59, mean age 39.9 years, 78 % female) were prospectively enrolled at four European MS centres, and reassessed after two years (MS, n = 242; HC, n = 30). Post-processing of 3 Tesla (3 T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient's white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient as a random factor, serum NfL, age, sex, timepoint for visit, diagnosis, treatment, and center as fixed factors were run. RESULTS: rLMM revealed significant associations between GD and serum NfL (t = 2.94, p = 0.003), age (t = 4.21, p = 2.5 × 10-5), and longitudinal changes in NfL (t = -2.29, p = 0.02), but not for sex (t = 0.63, p = 0.53) or treatments (t = 0.80-0.83, p = 0.41-0.42). Voxel-wise analyses revealed significant associations between dysconnectivity in cerebellar and brainstem regions and serum NfL (t = 7.03, p < 0.001). DISCUSSION: In our prospective multi-site MS cohort, rLMMs demonstrated that the extent of global and regional brain disconnectivity is sensitive to a systemic biomarker of axonal damage, serum NfL, in patients with MS. These findings provide a neuroaxonal correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and potential clinical relevance of brain disconnectome mapping in patients with brain disorders.

Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis.

BACKGROUND: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. OBJECTIVE: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. METHODS: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. RESULTS: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5-5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. CONCLUSION: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting.

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis.

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

Risk of fingolimod rebound after switching to cladribine or rituximab in multiple sclerosis.

BACKGROUND: A sudden onset of extensive disease activity, including severe clinical relapse and extensive brain or spinal magnetic resonance imaging (MRI) lesions, termed "rebound" disease activity has been reported after withdrawal of fingolimod in patients with multiple sclerosis (MS). OBJECTIVE: To compare the risk of rebound after switching from fingolimod to cladribine or rituximab in MS. METHODS: All patients switching from fingolimod to cladribine or rituximab were included in a retrospective cohort study utilizing prospectively collected data from two university hospitals with different treatment strategies. RESULTS: A total of 73 patients with at least 6 months follow-up after switching were identified, 33 patients had switched from fingolimod to cladribine and 40 patients to rituximab. No patients in the rituximab group and seven (21.1%) in the cladribine group qualified for rebound disease activity. Ten (30.3%) of the patients using cladribine and five (12.5%) of the patients using rituximab experienced a relapse. MRI disease activity was seen in 18 (54.5%) and eight (20.0%) of the patients using cladribine and rituximab, respectively. Younger age and previous high relapse rate were associated with increased risk of rebound in the cladribine group. CONCLUSIONS: We identify a lower risk of rebound during the first year after switching from fingolimod to rituximab compared to cladribine, indicating a better initial clinical outcome with the former treatment strategy.

Navigational tunnel technique for gastric peroral endoscopic pyloromyotomy: getting straight to the point (pylorus).

BACKGROUND AND AIMS: Gastric peroral endoscopic pyloromyotomy (G-POEM) is emerging as a treatment option for patients with gastroparesis. The most technically difficult part of the procedure is creating a submucosal tunnel in the gastric antrum, which can be directionally challenging. We describe a novel navigational tunneling method that guides submucosal dissection in the direction of the pylorus and helps to identify the pyloric landmarks. METHODS: Consecutive patients from September to December 2020 who underwent G-POEM for symptomatic gastroparesis were included. All cases were confirmed by prolonged gastric emptying study. The navigational tunnel technique was performed as follows: (1) mucosal cautery markings were made to outline the tunnel starting 3 to 4 cm proximal to the pylorus, (2) submucosal injection was done at the level of the pylorus and extended backward to the incision point, and (3) submucosal dissection was carried out after the prior submucosal injection straight to the pylorus. RESULTS: Six patients with gastroparesis underwent G-POEM with the navigational tunneling technique. The average time for submucosal injection was 2 minutes and 42 seconds, and the average tunnel time was 15 minutes and 36 seconds. There were no adverse events. All patients reported significant improvement (50%-85%) in symptoms. CONCLUSIONS: This novel navigational tunneling technique appears to guide and facilitate G-POEM by providing a visual path for submucosal dissection straight to the pylorus. It may increase efficiency, decreasing the need to repeatedly exit the tunnel to check direction and preventing nonproductive wandering. It may also help identify the pyloric ring within the tunnel.

Functional connectivity in multiple sclerosis modelled as connectome stability: A 5-year follow-up study.

BACKGROUND: Brain functional connectivity (FC) in multiple sclerosis (MS) is abnormal compared to healthy controls (HCs). More longitudinal studies in MS are needed to evaluate whether FC stability is clinically relevant. OBJECTIVE: To compare functional magnetic resonance imaging (fMRI)-based FC between MS and HC, and to determine the relationship between longitudinal FC changes and structural brain damage, cognitive performance and physical disability. METHODS: T1-weighted MPRAGE and resting-state fMRI (1.5T) were acquired from 70 relapsing-remitting MS patients and 94 matched HC at baseline (mean months since diagnosis 14.0 ± 11) and from 60 MS patients after 5 years. Independent component analysis and network modelling were used to measure longitudinal FC stability and cross-sectional comparisons with HC. Linear mixed models, adjusted for age and sex, were used to calculate correlations. RESULTS: At baseline, patients with MS showed FC abnormalities both within networks and in single connections compared to HC. Longitudinal analyses revealed functional stability and no significant relationships with clinical disability, cognitive performance, lesion or brain volume. CONCLUSION: FC abnormalities occur already at the first decade of MS, yet we found no relevant clinical correlations for these network deviations. Future large-scale longitudinal fMRI studies across a range of MS subtypes and outcomes are required.

EUS-guided blood patch delivery during liver biopsy: nature's gel foam.

Video 1Case 1 EUS liver biopsy with FNA needle complicated by persistent blood flow within biopsy tract, which is successfully treated with blood patch technique. Case 2 EUS liver biopsy with FNA needle complicated by persistent blood flow within biopsy tract, which is successfully treated with blood patch technique.

Pneumonitis and fibrosis after breast cancer radiotherapy: occurrence and treatment-related predictors.

BACKGROUND: Radiation pneumonitis (RP) and radiation fibrosis (RF) are common side effects after breast cancer (BC) radiotherapy (RT). However, there is a great variation in the frequency of RP and RF. This study presents the occurrence of- and the treatment-related predictors for RP and RF. Further, physician- and patient-reported pulmonary symptoms during the first year after postoperative RT for BC are demonstrated. MATERIALS AND METHODS: From 2007 to 2008, 250 BC patients referred for postoperative RT were included in a prospective cohort study and followed during the first year after RT. High-resolution computed tomography of the lungs and symptom registration were performed before RT and 3, 6, and 12 months after RT. Patient-reported symptoms were registered by standard quality of life questionnaires. Logistic regression analyses were applied to estimate treatment-related predictors for radiological RP (rRP), clinical RP (cRP), radiological RF (rRF), and clinical RF (cRF). RESULTS: The occurrence of rRP and cRP at three months was 78% and 19%, while 12 months after RT rRF and cRF was 89% and 16%, respectively; all reported as grade 1. In multivariable analyses, mastectomy predicted cRP at three months (OR = 2.48, p = .03) and cRF at six months, ipsilateral lung volume receiving 20 Gray or more (V20), V30, and mean lung dose (MLD) predicted rRP at six months (OR = 1.06, p = .0003; OR = 1.10, p = .001; and OR = 1.03, p = .01, respectively). Endocrine treatment predicted cRF at 12 months (OR = 2.48, p = .02). Physicians reported significant more dyspnea at 3 months (p = .003) and patients reported 'a little dyspnea' more at 3 and 12 months compared to baseline (p = .007). CONCLUSION: RP and RF are prevalent in the first year after BC radiation. Mastectomy predicted cRP at three months. V20, V30, D25, and MLD predicted rRP at 6 months, and endocrine treatment predicted cRF at 12 months. Patients and physicians reported dyspnea differently.

Successful use of a novel dynamic rigidizing overtube in a patient with looping during colonoscopy.

Video 1This video is our description of use of the novel dynamic rigidizing overtube in a challenging colonoscopy case in which looping was causing significant bradycardia and inability to advance the colonoscope to the cecum. The rigidizing overtube, through sequential cycles of its flexible and rigidized state, allowed for easy movement of the colonoscope to the cecum.

LesionQuant for Assessment of MRI in Multiple Sclerosis-A Promising Supplement to the Visual Scan Inspection.

Background and Goals: Multiple sclerosis (MS) is a central nervous system inflammatory disease where magnetic resonance imaging (MRI) is an important tool for diagnosis and disease monitoring. Quantitative measurements of lesion volume, lesion count, distribution of lesions, and brain atrophy have a potentially significant value for evaluating disease progression. We hypothesize that utilizing software designed for evaluating MRI data in MS will provide more accurate and detailed analyses compared to the visual neuro-radiological evaluation. Methods: A group of 56 MS patients (mean age 35 years, 70% females and 96% relapsing-remitting MS) was examined with brain MRI one and 5 years after diagnosis. The T1 and FLAIR brain MRI sequences for all patients were analyzed using the LesionQuant (LQ) software. These data were compared with data from structured visual evaluations of the MRI scans performed by neuro-radiologists, including assessments of atrophy, and lesion count. The data from LQ were also compared with data from other validated research methods for brain segmentation, including assessments of whole brain volume and lesion volume. Correlations with clinical tests like the timed 25-foot walk test (T25FT) were performed to explore additional value of LQ analyses. Results: Lesion count assessments by LQ and by the neuro-radiologist were significantly correlated one year (cor = 0.92, p = 2.2 × 10-16) and 5 years (cor = 0.84, p = 2.7 × 10-16) after diagnosis. Analyzes of the intra- and interrater variability also correlated significantly (cor = 0.96, p < 0.001, cor = 0.97, p < 0.001). Significant positive correlation was found between lesion volume measured by LQ and by the software Cascade (cor = 0.7, p < 0.001. LQ detected a reduction in whole brain percentile >10 in 10 patients across the time-points, whereas the neuro-radiologist assessment identified six of these. The neuro-radiologist additionally identified five patients with increased atrophy in the follow-up period, all of them displayed decreasing low whole brain percentiles (median 11, range 8-28) in the LQ analysis. Significant positive correlation was identified between lesion volume measured by LQ and test performance on the T25FT both at 1 and 5 years after diagnosis. Conclusion: For the number of MS lesions at both time-points, we demonstrated strong correlations between the assessments done by LQ and the neuro-radiologist. Lesion volume evaluated with LQ correlated with T25FT performance. LQ-analyses classified more patients to have brain atrophy than the visual neuro-radiological evaluation. In conclusion, LQ seems like a promising supplement to the evaluation performed by neuro-radiologists, providing an automated tool for evaluating lesions in MS patients and also detecting early signs of atrophy in both a longitudinal and cross-sectional setting.

Traditional serrated adenomas (TSA) and the company they keep: TSA presence predicts advanced neoplasm states.

BACKGROUND: The association of TSAs with metachronous neoplasms is well established and suggests that TSAs would also have an association with synchronous neoplasms. METHODS: We compared odds ratios and rates of synchronous neoplasms found in colonoscopies with and without TSAs. RESULTS: There was a mean of 2.44 neoplasms among TSA cases in comparison with 1.72 in non-TSA cases. The odds ratio for advanced neoplasia was highest among cases with one or more TSAs relative to cases with one or more HPs (7.54 [CI, 4.23-13.44]) when compared with adenomas (1.95 [CI, 1.75-2.17]) and SSPs (2.98 [CI, 2.54-3.5]). CONCLUSIONS: In this study population, there is a 7-fold higher risk of synchronous advanced neoplasms among cases with one or more TSAs.

Nonablative Radiofrequency Treatment for Gastroesophageal Reflux Disease (STRETTA).

Gastroesophageal reflux disease (GERD) is the most frequent outpatient diagnosis in the United States. There has been significant development in the endoscopic treatment of GERD, with several devices that have reached the market. One of the endoscopic devices for the management of GERD in the United States is the Stretta system. This procedure uses radiofrequency energy, which is applied to the muscles of the lower esophageal sphincter and the gastric cardia resulting in an improvement of reflux symptoms. This review evaluates the most recent data on the efficacy, mechanisms of action, and safety of this procedure.

Neurodegenerative Interplay of Cardiovascular Autonomic Dysregulation and the Retina in Early Multiple Sclerosis.

Introduction: Autonomic nervous system (ANS) symptoms are prevalent in multiple sclerosis (MS) as is neurodegeneration. Our aim was to explore the occurrence of ANS symptoms and retinal neurodegeneration in a newly diagnosed MS population with tools available in a clinical setting. Methods: Forty-three MS patients and 44 healthy controls took part in the study. We employed a bedside cardiovascular ANS test battery together with classical pupillometry, optical coherence tomography (OCT) evaluation of retinal neurodegeneration in eyes without previous optic neuritis (MSNON) and patients' self-report forms on fatigue, orthostatic and ANS symptoms. Results: Half of the patients presented with ANS symptoms and a high level of fatigue. There was a significant difference in ganglion cell layer thickness (mean GCIPL) evaluated by OCT in MSNON compared to healthy control eyes. We found a negative linearity of mean GCIPL on group level with increasing disease duration. Three patients fulfilled the criteria of postural orthostatic tachycardia syndrome (POTS). Conclusion: Our results demonstrate retinal neurodegeneration in MSNON, a high frequency of fatigue and a high prevalence of ANS symptoms in newly diagnosed patients. Whether neurodegeneration precedes ANS dysfunction or vice versa is still open to debate, but as unveiled by the presence of POTS in this MS population, differences in stress-response regulation add to the understanding of variation in onset-time of ANS dysfunction in early MS.

Cross-Sectional and Longitudinal MRI Brain Scans Reveal Accelerated Brain Aging in Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disorder of the central nervous system. By combining longitudinal MRI-based brain morphometry and brain age estimation using machine learning, we tested the hypothesis that MS patients have higher brain age relative to chronological age than healthy controls (HC) and that longitudinal rate of brain aging in MS patients is associated with clinical course and severity. Seventy-six MS patients [71% females, mean age 34.8 years (range 21-49) at inclusion] were examined with brain MRI at three time points with a mean total follow up period of 4.4 years (±0.4 years). We used additional cross-sectional MRI data from 235 HC for case-control comparison. We applied a machine learning model trained on an independent set of 3,208 HC to estimate individual brain age and to calculate the difference between estimated and chronological age, termed brain age gap (BAG). We also assessed the longitudinal change rate in BAG in individuals with MS. MS patients showed significantly higher BAG (4.4 ± 6.6 years) compared to HC (Cohen's D = 0.69, p = 4.0 × 10-6). Longitudinal estimates of BAG in MS patients showed high reliability and suggested an accelerated rate of brain aging corresponding to an annual increase of 0.41 (SE = 0.15) years compared to chronological aging (p = 0.008). Multiple regression analyses revealed higher rate of brain aging in patients with more brain atrophy (Cohen's D = 0.86, p = 4.3 × 10-15) and increased white matter lesion load (WMLL) (Cohen's D = 0.55, p = 0.015). On average, patients with MS had significantly higher BAG compared to HC. Progressive brain aging in patients with MS was related to brain atrophy and increased WMLL. No significant clinical associations were found in our sample, future studies are warranted on this matter. Brain age estimation is a promising method for evaluation of subtle brain changes in MS, which is important for predicting clinical outcome and guide choice of intervention.