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Background: Cognitive dysfunction and brain atrophy are both common in progressive multiple sclerosis (MS) but are seldom examined comprehensively in clinical trials. Antioxidant treatment may affect the neurodegeneration characteristic of progressive MS and slow its symptomatic and radiographic correlates. Objectives: This study aims to evaluate cross-sectional associations between cognitive battery components of the Brief International Cognitive Assessment for Multiple Sclerosis with whole and segmented brain volumes and to determine if associations differ between secondary progressive (SPMS) and primary progressive (PPMS) MS subtypes. Design: The study was based on a baseline analysis from a multi-site randomized controlled trial of the antioxidant lipoic acid in veterans and other people with progressive MS (NCT03161028). Methods: Cognitive batteries were conducted by trained research personnel.MRIs were processed at a central processing site for maximum harmonization. Semi- partial Pearson's adjustments evaluated associations between cognitive tests and MRI volumes. Regression analyses evaluated differences in association patterns between SPMS and PPMS cohorts. Results: Of the 114 participants, 70% had SPMS. Veterans with MS made up 26% (n = 30) of the total sample and 73% had SPMS. Participants had a mean age of 59.2 and sd 8.5 years, and 54% of them were women, had a disease duration of22.4 (sd 11.3) years, and had amedian Expanded Disability Status Scale of 6.0 (with an interquartile range of 4.0-6.0,moderate disability). The Symbol Digit Modalities Test (processing speed) correlated with whole brain volume (R = 0.29, p = 0.01) and total white matter volume (R = 0.33, p < 0.01). Both the California Verbal Learning Test (verbal memory) and Brief Visuospatial Memory Test-Revised (visual memory) correlated withmean cortical thickness (R = 0.27, p = 0.02 and R = 0.35, p < 0.01, respectively). Correlation patterns were similar in subgroup analyses. Conclusion: Brain volumes showed differing patterns of correlation across cognitive tasks in progressive MS. Similar results between SPMS and PPMS cohorts suggest combining progressiveMS subtypes in studies involving cognition and brain atrophy in these populations. Longitudinal assessment will determine the therapeutic effects of lipoic acid on cognitive tasks, brain atrophy, and their associations. [ABSTRACT FROM AUTHOR]

Objective. Aquaporin-4 (AQP4) serum autoantibodies are detected by a variety of methods. The highest sensitivity is achieved with cell-based assays, but the enzyme-linked immunosorbent assay (ELISA) is still commonly utilized by clinicians worldwide. Methods. We performed a retrospective review to identify all patients at the University of Utah who had AQP4 ELISA testing at ARUP Laboratories from 2010 to 2017. We then reviewed their diagnostic evaluation and final diagnosis based on the ELISA titer result. Results. A total of 750 tests for the AQP4 ELISA were analyzed, and 47 unique patients with positive titers were identified. Less than half of these patients (49%) met the clinical criteria for neuromyelitis optica spectrum disorder (NMOSD). In cases of low positive titers (3.0–7.9 U/mL, n = 19), the most common final diagnosis was multiple sclerosis (52.6%). In the moderate positive cohort (8.0–79.9 U/mL, n = 14), only a little more than half the cohort (64.3%) had NMOSD. In cases with high positives (80–160 U/mL, n = 14), 100% of patients met clinical criteria for NMOSD. Conclusions. Our data illustrates diagnostic uncertainty associated with the AQP4 ELISA, an assay that is still commonly ordered by clinicians despite the availability of more sensitive and specific tests to detect AQP4 autoantibodies in patients suspected of having NMOSD. In particular, low positive titer AQP4 ELISA results are particularly nonspecific for the diagnosis of NMOSD. The importance of accessibility to both sensitive and specific AQP4 testing cannot be overemphasized in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To compare progressive motor impairment onset attributable to a "critical" central nervous system (CNS) demyelinating lesion in patients with highly restricted versus unlimited magnetic resonance imaging (MRI) lesion burden. Methods: We identified 135 patients with progressive motor impairment for ⩾1 year attributable to a "critical" demyelinating lesion with: MRI burden of 1 lesion ("progressive solitary sclerosis"), 2–5 lesions ("progressive paucisclerosis"), or unrestricted (>5) lesions and "progressive unilateral hemiparesis." Neuroradiology review of brain and spinal cord MRI documented unequivocally demyelinating lesions. Results: A total of 33 (24.4%) patients had progressive solitary sclerosis; 56 (41.5%) patients had progressive paucisclerosis; and 46 (34.1%) patients had progressive unilateral hemiparesis. Median age at onset of progressive motor impairment was younger in progressive solitary sclerosis (49 years; range 24–73) and progressive paucisclerosis (50 years; range 30–64) than in progressive unilateral hemiparesis (54 years; range 39–77; p = 0.02 and p = 0.003, respectively). Within progressive unilateral hemiparesis, motor-progression onset was similar between those with 4–10, 11–20, or >20 brain lesions (55, 54, 53 years of age, respectively; p = 0.44). Conclusion: Motor-progression age is similar, but paradoxically earlier, in cohorts with highly restricted CNS lesion burden than in those with unrestricted lesion burden with progressive unilateral hemiparetic MS. The "critical" demyelinating lesion rather than total brain MRI lesion burden is the major contributor to motor-progression onset in these cohorts. [ABSTRACT FROM AUTHOR]

Objective: To report progressive motor impairment from a critically located central nervous system (CNS) demyelinating lesion in patients with restricted magnetic resonance imaging (MRI)-lesion burden. Methods: We identified 38 patients with progressive upper motor-neuron impairment for >1 year, 2–5 MRI CNS-demyelinating lesions, with one seemingly anatomically responsible for progressive motor impairment. Patients with any alternative etiology for progressive motor impairment were excluded. A neuroradiologist blinded to clinical evaluation reviewed multiple brain and spinal-cord MRI, selecting a candidate critically located demyelinating lesion. Lesion characteristics were determined and subsequently compared with clinical course. Results: Median onset age was 47.5 years (24–64); 23 (61%) women. Median follow-up was 94 months (18–442); median Expanded Disability Status Scale Score (EDSS) at last follow-up was 4.5 (2–10). Clinical presentations were progressive: hemiparesis/monoparesis 31; quadriparesis 5; and paraparesis 2; 27 patients had progression from onset; 11 progression post-relapse. Total MRI lesions were 2 (n = 8), 3 (n = 12), 4 (n = 12), and 5 (n = 6). Critical lesions were located on corticospinal tracts, chronically atrophic in 26/38 (68%) and involved cervical spinal cord in 27, cervicomedullary/brainstem region in 6, thoracic spinal cord in 4, and subcortical white matter in 1. Conclusion: Progressive motor impairment may ascribe to a critically located CNS-demyelinating lesion in patients with highly restricted MRI burden. Motor progression from a specific demyelinating lesion has implications for understanding multiple sclerosis (MS) progression. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The gold-standard tool for colorectal cancer detection is colonoscopy, but it provides only mucosal surface visualization. Ultrasound biomicroscopy allows a clear delineation of the epithelium and adjacent colonic layers. The aim of this study was to design a system to generate endoluminal ultrasound biomicroscopic images of the mouse colon, in vivo, in an animal model of inflammation-associated colon cancer. Materials and Methods: Thirteen mice (Mus musculus) were used. A 40-MHz miniprobe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope. Control mice (n = 3) and mice treated with azoxymethane and dextran sulfate sodium (n = 10) were subjected to simultaneous endoluminal ultrasound biomicroscopy and white-light colonoscopy. The diagnosis obtained with endoluminal ultrasound biomicroscopy and colonoscopy was compared and confirmed by postmortem histopathology. Results: Endoluminal ultrasound biomicroscopic images showed all layers of the normal colon and revealed lesions such as lymphoid hyperplasias and colon tumors. Additionally, endoluminal ultrasound biomicroscopy was able to detect two cases of mucosa layer thickening, confirmed by histology. Compared to histologic results, the sensitivities of endoluminal ultrasound biomicroscopy and colonoscopy were 0.95 and 0.83, respectively, and both methods achieved specificities of 1.0. Conclusions: Endoluminal ultrasound biomicroscopy can be used, in addition to colonoscopy, as a diagnostic method for colonic lesions. Moreover, experimental endoluminal ultrasound biomicroscopy in mouse models is feasible and might be used to further develop research on the differentiation between benign and malignant colonic diseases. [ABSTRACT FROM AUTHOR]

Background: Recruitment for progressive multiple sclerosis (PMS) randomized clinical trials (RCTs) is challenging due to 1) lack of standard definitions of PMS, 2) varying duration of progression prior to entry, 3) restricted age and disability requirements, 4) lack of specific outcome measures with associated sample sizes, 5) poorly understood PMS natural history, 6) integration of prior and/or current treatments with diseasemodifying therapies (DMTs), 7) integration of emerging DMTs specific for PMS, and 8) over-the-counter availability of some investigational agents (eg, lipoic acid [LA], biotin). The resulting narrow inclusion criteria makes recruitment for clinical trials difficult, and raises concerns regarding generalizability of the results. Objectives: To describe the varying successes of recruitment approaches used in a current multisite RCT for PMS, compare the resulting study population to other PMS trial populations, and consider if the population is reflective of the general PMS population. Methods: Describe recruitment methods for Lipoic Acid for Treatment of Progressive MS RCT (LAPMS; trial registration: NCT03161028). Present the demographic characteristics of the subjects and compare to other PMS study populations and to a general reference PMS population. Results: LAPMS is a 2-year, multisite, phase 2, double-blind RCT of LA in PMS (n = 118, currently 71% randomized). Enrollment criteria: age ≥18 years, non--relapse-related MS clinical worsening in prior 2 years, worsening ≥ 1 year if on concurrent DMT, Expanded Disability Status Scale (EDSS) score 3.0-6.5, and without non--MS-related ambulation deficits. Recruitment sources are direct from clinic (63.1%), physician referral (23.8%), community outreach/MS events (3.6%), local repository (3.6%), Tiny URL promotion/National MS Society website (2.4%), Facebook advertisement (2.4%), and a North American Research Committee on Multiple Sclerosis (NARCOMS) recruitment letter (1.2%). Participants have mean age 59.4 (8.1) years, 36 (49.3%) females, median EDSS score of 6.0 (3.0-6.5), mean 23.0 (11.7) years since symptom onset, and 9 (12.3%) subjects without previous DMT. Mean LAPMS population age and disease duration are higher than those of study populations in the EXPAND SPMS trial and ORATORIO PPMS trial. While similar to the EXPAND trial, LAPMS has higher EDSS levels than the ORATORIO population. Updates and comparison to a general PMS population will be presented. Conclusions: Restrictive PMS recruitment criteria create differences in PMS trial populations as well as raise concerns about generalizability of results to wider PMS populations. Approaches to addressing these issues are discussed. [ABSTRACT FROM AUTHOR]

Enhancing myelin repair remains an important therapeutic goal in primary demyelinating diseases of the central nervous system (CNS) such as multiple sclerosis (MS). The emerging heterogeneity of pathology within MS lesions, and differential oligodendrocyte survival in particular, suggests that therapeutic strategies may need to be tailored to ah individual patient's requirements. A number of therapeutic strategies have been proposed to enhance myelin repair in the CNS: cell transplantation, growth factor therapy, and antibody therapy, bur each proposed therapy has different implications with respect to pathogenetic mechanisms of demyelination. Of these, antibody therapy is the most amenable to immediate application in patients--but a combination of therapeutic approaches may be required in practice. [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation To describe patient clinical characteristics associated with matched oligoclonal bands (OCB).A retrospective review at the University of Utah examined patients with matched OCB from 2015 to 2020. Clinical data, diagnosis, and outcomes were collected. Patients were classified with either multiple sclerosis (MS), other inflammatory neurologic disorder (other‐IND), or noninflammatory neurologic disorder (NIND).Of 539 identified patients, 436 (53.4% female) were matched‐only, while 103 (43.7% female) were matched + unique. Patients with matched‐only bands were older (57.4 ± 16 vs. 52 ± 14.2, p < 0.001) and more likely to have a history of autoimmune disease (40.1% vs. 28.2%, p = 0.024) and/or cancer (28.7% vs. 16.5%, p = 0.012). Patients with matched + unique bands were more likely to have CSF pleocytosis (52.4% vs. 25.9%, p < 0.001), high IgG index (52.2% vs. 7.6%, p < 0.001), and an abnormal MRI (86.9% vs. 63.1%, p < 0.001). More than two‐thirds of matched‐only patients had NIND, while 33% and 41.7% of matched + unique patients had MS and other‐IND, respectively. Patients exhibiting matched‐only bands and a high IgG index demonstrated a significantly higher incidence of other‐IND compared to those with matched‐only bands and a normal IgG index (55.6% vs. 30.4%, p = 0.013). While Kaplan–Meier survival curves demonstrated higher mortality in the matched‐only cohort compared to the matched + unique cohort (p = 0.02), multivariable Cox regression analysis showed this difference was not statistically significant when adjusting for various factors. A history of cancer was the significant predictor of increased mortality risk (Hazard ratio = 3.147, 95% CI [2.196, 4.51]).Patients with matched only versus matched + unique OCB have distinct clinical profiles. [ABSTRACT FROM AUTHOR]

We present a case of a 58-year-old man with a history of severe discoid lupus erythematosus and acute encephalopathy and incoordination. Antinuclear antibody testing was weakly positive but all other laboratory tests for systemic lupus erythematosus were negative and serum quantitative immunoglobulins and lymphocytes were normal. MRI brain showed T2/FLAIR hyperintensities within the bilateral parietal and temporal lobes with involvement of subcortical U fibers. CSF PCR was negative for varicella-zoster virus, herpes simplex, JCV and BK virus. However, JCV antibody index was elevated (3.88; reference: < 0.2). Right parietal brain biopsy was consistent with JCV infection and diagnostic of progressive multifocal leukoencephalopathy (PML). To the best of our knowledge, this is the first reported case of PML in a patient with discoid lupus without other traditional risk factors for the disease and highlights the need for clinical vigilance in this patient population., (Published by Elsevier B.V.)

Objectives: Rapid on-site evaluation (ROSE) by cytopathologists during endoscopic ultrasound-fine-needle aspiration (EUS-FNA) of solid pancreatic lesions (SPLs) improves adequacy and diagnostic accuracy while reducing the number of needle passes. We evaluated the usefulness of ROSE performed by the endosonographer., Methods: Patients with an SPL were randomly assigned to EUS-FNA with ROSE or non-ROSE. Procedure duration, number of needle passes, specimen adequacy, and adverse event rates were compared., Results: Sixty-five patients were enrolled (33 in the ROSE vs 32 in the non-ROSE group). Both groups were similar in terms of age, sex, size, and location of the lesion. Specimen adequacy rates were high and similar between groups. Mean (standard deviation) procedure duration was shorter in the ROSE versus non-ROSE group (30.0 [11.3] vs 37.0 [7.2] minutes, P < 0.005), as well as the mean (standard deviation) number of needle passes (2.6 [0.8] vs 3.5 [0.8], P < 0.005). Accuracy parameters as sensitivity and accuracy of ROSE by the endosonographer for malignancy were 93% and 88%, respectively., Conclusions: After specific training, the endosonographer can accurately evaluate samples during EUS-FNA of SPL, allowing for a shorter procedure duration and a lower number of needle passes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare progressive motor impairment onset attributable to a "critical" central nervous system (CNS) demyelinating lesion in patients with highly restricted versus unlimited magnetic resonance imaging (MRI) lesion burden., Methods: We identified 135 patients with progressive motor impairment for ⩾1 year attributable to a "critical" demyelinating lesion with: MRI burden of 1 lesion ("progressive solitary sclerosis"), 2-5 lesions ("progressive paucisclerosis"), or unrestricted (>5) lesions and "progressive unilateral hemiparesis." Neuroradiology review of brain and spinal cord MRI documented unequivocally demyelinating lesions., Results: A total of 33 (24.4%) patients had progressive solitary sclerosis; 56 (41.5%) patients had progressive paucisclerosis; and 46 (34.1%) patients had progressive unilateral hemiparesis. Median age at onset of progressive motor impairment was younger in progressive solitary sclerosis (49 years; range 24-73) and progressive paucisclerosis (50 years; range 30-64) than in progressive unilateral hemiparesis (54 years; range 39-77; p  = 0.02 and p  = 0.003, respectively). Within progressive unilateral hemiparesis, motor-progression onset was similar between those with 4-10, 11-20, or >20 brain lesions (55, 54, 53 years of age, respectively; p  = 0.44)., Conclusion: Motor-progression age is similar, but paradoxically earlier, in cohorts with highly restricted CNS lesion burden than in those with unrestricted lesion burden with progressive unilateral hemiparetic MS. The "critical" demyelinating lesion rather than total brain MRI lesion burden is the major contributor to motor-progression onset in these cohorts.

Hip joint instability has been targeted as an important issue that affects normal hip function. The diagnosis of hip instability could be very challenging and currently, there is no definitive diagnostic test. Hip instability results in an excessive amount of translation of femoroacetabular articulation, leading to changes on the dynamic loading of the hip. These changes in femoroacetabular translation could be evaluated by human movement analysis methods. The purpose of this study was to describe the triaxial and overall magnitude of acceleration in patients diagnosed with hip instability during gait cycle and compare those results with a control group. Our hypothesis was that acceleration values obtained from the instability group would be higher than asymptomatic controls. Ten patients with previously diagnosed hip instability were included and 10 healthy and asymptomatic subjects were enrolled as control group. Triaxial accelerometers attached bilaterally to the skin over the greater trochanter were used to record acceleration during walking on a treadmill. The overall magnitude of acceleration and the axial, anteroposterior and mediolateral accelerations ( x / y / z ) were obtained during gait. Mean overall magnitude of acceleration was higher in the hip instability group compared with the control group, 1.51 g (SD: 0.23) versus 1.07 g (SD: 0.16) ( P = 0.022). The axial, anteroposterior and mediolateral accelerations significantly differed between the two groups. The axial and mediolateral accelerations showed to be higher for the hip instability group while the anteroposterior axis acceleration was lower., (© The Author(s) 2019. Published by Oxford University Press.)

Objective: To report progressive motor impairment from a critically located central nervous system (CNS) demyelinating lesion in patients with restricted magnetic resonance imaging (MRI)-lesion burden., Methods: We identified 38 patients with progressive upper motor-neuron impairment for >1 year, 2-5 MRI CNS-demyelinating lesions, with one seemingly anatomically responsible for progressive motor impairment. Patients with any alternative etiology for progressive motor impairment were excluded. A neuroradiologist blinded to clinical evaluation reviewed multiple brain and spinal-cord MRI, selecting a candidate critically located demyelinating lesion. Lesion characteristics were determined and subsequently compared with clinical course., Results: Median onset age was 47.5 years (24-64); 23 (61%) women. Median follow-up was 94 months (18-442); median Expanded Disability Status Scale Score (EDSS) at last follow-up was 4.5 (2-10). Clinical presentations were progressive: hemiparesis/monoparesis 31; quadriparesis 5; and paraparesis 2; 27 patients had progression from onset; 11 progression post-relapse. Total MRI lesions were 2 ( n = 8), 3 ( n = 12), 4 ( n = 12), and 5 ( n = 6). Critical lesions were located on corticospinal tracts, chronically atrophic in 26/38 (68%) and involved cervical spinal cord in 27, cervicomedullary/brainstem region in 6, thoracic spinal cord in 4, and subcortical white matter in 1., Conclusion: Progressive motor impairment may ascribe to a critically located CNS-demyelinating lesion in patients with highly restricted MRI burden. Motor progression from a specific demyelinating lesion has implications for understanding multiple sclerosis (MS) progression.

The development of high-frequency endoscopic ultrasound for the investigation of models of esophageal disease may offer insights for future translation to human imaging. With respect to small animal models of esophageal diseases, ultrasound imaging instrumentation must employ frequencies scaled up to maintain the compromise between image resolution and inspected region. In this sense, a 40-MHz endoluminal ultrasound biomicroscopy (eUBM) system and an endoscope were tested as diagnostic methods of imaging rat esophageal lesions in the acute and chronic phases caused by sodium hydroxide. Although endoscopy allowed grading of the esophagus in accordance with a classification specific to the epithelial alterations and including hyperemia, edema, exudates, fibrin and superficial and deep ulcerations, the eUBM images yielded the detection of superficial and deep ulcerations, as well as wall alterations caused by edema and inflammatory infiltrate in the submucosa. Additionally, eUBM enabled wall thickness measurements, which were statistically significantly increased (p < 0.05) in the acute phase., (Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension., Aim: We evaluated the effects of simvastatin on hepatic venous pressure gradient (HVPG) and azygos vein blood flow in cirrhotic patients., Methods: A 3-month prospective, randomized, triple-blind trial with simvastatin (40 mg/day) vs. placebo was conducted in patients with cirrhotic portal hypertension. HVPG and azygos blood flow, measured by colour Doppler endoscopic ultrasound, were assessed before and after treatment. The primary endpoint was a decrease in the HVPG of at least 20% from baseline or to ≤12 mmHg after the treatment., Results: 34 patients were prospectively enrolled, and 24 completed the protocol. In the simvastatin group 6/11 patients (55%) presented a clinically relevant decrease in the HVPG; no decrease was observed in the placebo group (p=0.036). Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin. HVPG and azygos blood flow values were not correlated. No significant adverse events occurred., Conclusion: Simvastatin lowers portal pressure and may even improve liver function. The haemodynamic effect appears to be more evident in patients with severe portal hypertension., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate the potential use of colonoscopy and endoluminal ultrasonic biomicroscopy (eUBM) to track the progression of mouse colonic lesions., Methods: Ten mice were treated with a single azoxymethane intraperitoneal injection (week 1) followed by seven days of a dextran sulfate sodium treatment in their drinking water (week 2) to induce inflammation-associated colon tumors. eUBM was performed simultaneously with colonoscopy at weeks 13, 17-20 and 21. A 3.6-F diameter 40 MHz mini-probe catheter was used for eUBM imaging. The ultrasound mini-probe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope, allowing simultaneous acquisition of colonoscopic and eUBM images. During image acquisition, the mice were anesthetized with isoflurane and kept in a supine position over a stainless steel heated surgical waterbed at 37 °C. Both eUBM and colonoscopic images were captured and stored when a lesion was detected by colonoscopy or when the eUBM image revealed a modified colon wall anatomy. During the procedure, the colon was irrigated with water that was injected through a flush port on the mini-probe catheter and that acted as the ultrasound coupling medium between the transducer and the colon wall. Once the acquisition of the last eUBM/colonoscopy section for each animal was completed, the colons were fixed, paraffin-embedded, and stained with hematoxylin and eosin. Colon images acquired at the first time-point for each mouse were compared with subsequent eUBM/colonoscopic images of the same sites obtained in the following acquisitions to evaluate lesion progression., Results: All 10 mice had eUBM and colonoscopic images acquired at week 13 (the first time-point). Two animals died immediately after the first imaging acquisition and, consequently, only 8 mice were subjected to the second eUBM/colonoscopy imaging acquisition (at the second time-point). Due to the advanced stage of colonic tumorigenesis, 5 animals died after the second time-point image acquisition, and thus, only three were subjected to the third eUBM/colonoscopy imaging acquisition (the third time-point). eUBM was able to detect the four layers in healthy segments of colon: the mucosa (the first hyperechoic layer moving away from the mini-probe axis), followed by the muscularis mucosae (hypoechoic), the submucosa (the second hyperechoic layer) and the muscularis externa (the second hypoechoic layer). Hypoechoic regions between the mucosa and the muscularis externa layers represented lymphoid infiltrates, as confirmed by the corresponding histological images. Pedunculated tumors were represented by hyperechoic masses in the mucosa layer. Among the lesions that decreased in size between the first and third time-points, one of the lesions changed from a mucosal hyperplasia with ulceration at the top to a mucosal hyperplasia with lymphoid infiltrate and, finally, to small signs of mucosal hyperplasia and lymphoid infiltrate. In this case, while lesion regression and modification were observable in the eUBM images, colonoscopy was only able to detect the lesion at the first and second time-points, without the capacity to demonstrate the presence of lymphoid infiltrate. Regarding the lesions that increased in size, one of them started as a small elevation in the mucosa layer and progressed to a pedunculated tumor. In this case, while eUBM imaging revealed the lesion at the first time-point, colonoscopy was only able to detect it at the second time-point. All colonic lesions (tumors, lymphoid infiltrate and mucosal thickening) were identified by eUBM, while colonoscopy identified just 76% of them. Colonoscopy identified all of the colonic tumors but failed to diagnose lymphoid infiltrates and increased mucosal thickness and failed to differentiate lymphoid infiltrates from small adenomas. During the observation period, most of the lesions (approximately 67%) increased in size, approximately 14% remained unchanged, and 19% regressed., Conclusion: Combining eUBM with colonoscopy improves the diagnosis and the follow-up of mouse colonic lesions, adding transmural assessment of the bowel wall.

Background: Extra corporeal life support (ECLS) has been recently introduced in the treatment of refractory cardiac arrest (CA). Several studies have assessed the use of ECLS in refractory CA once the patients reach hospital. The time between CA and the implementation of ECLS is a major prognostic factor for survival. The main predictive factor for survival is ECLS access time. Pre hospital ECLS implementation could reduce access time. We therefore decided to assess the feasibility and safety of prehospital ECLS implementation (PH-ECLS) in a pilot study., Methods and Results: From January 2011 to January 2012, PH-ECLS implementation for refractory CA was performed in 7 patients by a PH-ECLS team including emergency and/or intensivist physicians and paramedics. Patients were included prospectively and consecutively if the following criteria were met: they had a witnessed CA; CPR was initiated within the first 5 min of CA and/or there were signs of life during CPR; an PH-ECLS team was available and absence of severe comorbidities. ECLS flow was established in all patients. ECLS was started 22 min (±6) after the incision, and 57 min (±21) after the onset of advanced cardiovascular life support (ACLS). In one patient, ECLS was stopped for 10 min due to an accidental decannulation. One patient survived without sequelae. Three patients developed brain death., Conclusions: This pilot study suggests that PH-ECLS performed by non-surgeons is safe and feasible. Further studies are needed to confirm the time saved by this strategy and its potential effect on survival., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The present work tested the capability of ultrasound biomicroscopy (UBM), at 45 MHz, to provide cross-sectional images with appropriate resolution and contrast to detect tumors and determine their penetration depths on the colon of mice, Mus musculus (Linnaeus 1758), treated with carcinogen for colon tumor induction. B-mode images were obtained, in vitro, from each animal (13 treated and 4 untreated) colon opened longitudinally and immersed in saline solution at room temperature. Prior to UBM inspection, all animals were also examined by colonoscopy. The layers of normal colon identified by UBM are: mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic) and muscularis externa (hypoechoic). UBM images of colon lesions presented structures corresponding to tumors (hyperechoic), lymphoid hyperplasia (hypoechoic) and polypoid tumors (hyperechoic). Additionally, tumoral lesion invasion through the colon was also identified. When compared with histopathologic analysis, all colon lesions detected by UBM were confirmed, while colonoscopic findings had two false negatives., (Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Increase in flow rate within the azygos vein may be used as an indicator of the degree of liver cirrhosis. The aim of this study was to evaluate the error in measurement of flow rate using a commercial endoscopic ultrasound system, using a flow phantom that mimicked azygos vein depth, diameter and flow rate. Diameter was underestimated in all cases, with an average underestimation of 0.09 cm. Maximum velocity was overestimated, by 4 ± 4% at 50°, 11 ± 3% at 60° and 23 ± 7% at 70°. The increase in error with beam-vessel angle is consistent with the error as arising from geometric spectral broadening. Flow was underestimated by amounts up to 33%, and it is noted that the overestimation caused by geometric spectral broadening is in part compensated by underestimation of diameter. It was concluded that measurement of flow rate using a commercially available endoscopic ultrasound system is dependent on the beam-vessel angle, with errors up to 33% for typical vessel depths, diameter and beam-vessel angle., (Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to show the feasibility of 50-MHz ultrasound biomicroscopy (UBM) to image the rat colon., Methods: B-mode images were obtained from ex vivo colon samples (n = 4) collected from Rattus norvegicus (Berkenhout, 1769) rats, with 2,4,6-trinitrobenzene sulfonic acid-induced colitis in 3 of them. Left colon rectangular fragments (5 x 5 mm) were obtained after necropsy, and UBM images were acquired with the samples immersed in saline at 37 degrees C. All layers of the normal intestinal wall were analyzed according to their thickness and the presence of uneven bowel mucosa (ulcers). The folds and layers detected by UBM were correlated with histopathologic analysis., Results: The 4 layers of the normal colon were identified on the UBM images: the mucosa (hyperechoic), muscularis mucosae (hypoechoic), submucosa (hyperechoic), and muscularis externa (hypoechoic). On 2 UBM images, superficial ulcers were detected, approximately 0.5 mm in size, with intestinal involvement limited to the mucosa. The histopathologic analysis verified enlargement of submucosa layers due to an edema associated with sub-mucosa leukocyte infiltration. On 1 UBM image, it was possible to detect a deep ulcer, which was confirmed by the light microscopic analysis., Conclusions: An ultrasound imaging system was scaled and optimized to visualize the rat colon. Ultrasound biomicroscopy provided axial and lateral resolutions close to 25 and 45 mum, respectively, and adequate penetration depth to visualize the whole thickness of an inflamed colon. The system identified the colon layers and was able to detect mural changes and superficial ulcers on the order of 500 mum.

Laparoscopy is now a reliable method for staging gastrointestinal cancer, orienting the therapy, and avoiding unnecessary laparotomy. Natural orifice transluminal endoscopic surgery (NOTES) is an emerging concept with potential advantages for patient recovery. The first case of clinical diagnostic application of transvaginal NOTES for diagnostic cancer staging is presented. Informed consent and Institutional Commission approval were obtained for transvaginal clinical trials. On February 28, 2007, a patient with elective surgical indication for diagnostic cancer staging was submitted to transvaginal NOTES procedure, and intra- and postoperative parameters were documented. In a 50-year-old female patient presenting with ascitis, diffuse abdominal pain, and weight loss for 2 months, diagnosis of peritoneal carcinomatosis was suspected, which was also found when a CT scan was performed. Transvaginal NOTES was used for diagnostic staging of the patient, using a colonoscope introduced into the abdomen through a small incision in the vagina. Biopsies of liver, diaphragm, ovaries, and peritoneum were successfully performed. Operative time was 105 min, vaginal access and closure was obtained in 15 min. Abdominal inventory was reliable, and all 16 biopsies taken were positive for ovarian adenocarcinoma. The patient was dismissed 48 hours after the procedure without complications. Recent literature and experience of the study group suggest possibilities for preliminary clinical applications by transvaginal natural orifice surgery for diagnostic purposes.

Carbonyl reduction is a main but undesired metabolic pathway of the anti-cancer drug daunorubicin (DRC). The resulting alcohol metabolite daunorubicinol has a far less anti-tumor potency and, in addition, is responsible for the life-threatening cardiac toxicity that limits the clinical use of DRC. Elevated levels of carbonyl-reducing enzymes in cancer cells may therefore contribute to the development of DRC chemoresistance and affect the clinical outcome. In the present investigation, human pancreas carcinoma cells were transfected with three important DRC reductases, namely carbonyl reductase (CBR1), aldehyde reductase (AKR1A1) and aldose reductase (AKR1B1), and levels of resistance towards DCR determined. Overexpression of all three reductases lead to a higher DRC inactivation and to an elevation of chemoresistance (7-fold for CBR1, 4.5-fold for AKR1A1 and 3.7-fold for AKR1B1), when IC(50)-values were considered. Coadministration of DRC reductase inhibitors in DRC chemotherapy may be desirable since this would reduce the formation of the cardiotoxic alcohol metabolite and prevent drug resistance.

A set of antibodies capable of binding glial cells promotes remyelination in models of multiple sclerosis (MS). Within this set, the mouse antibody, SCH94.03, was immunomodulatory implying that immune system mobilization might be integral to remyelination. We evaluated whether the human remyelination-promoting antibody rHIgM22 influences acquired immunity. The antibody did not bind to immune cells, or influence humoral immune responses, antigen presentation, T cell proliferation or cytokine production. Treatment with rHIgM22 had no effect on demyelination or virus infection in two disease models. These results demonstrate that the remyelination-promoting activity of antibody rHIgM22 is not dependent on immunomodulation.

The human monoclonal IgM antibody sHIgM22 and mouse IgM monoclonal antibody 94.03 bind to oligodendrocytes, induce calcium signals in cultured glial cells, and promote remyelination in mouse models of multiple sclerosis. In order to address the mechanisms employed by these antibodies to promote CNS repair, bivalent monomers, F(ab')2 fragments, and monovalent forms of these antibodies were investigated to determine whether they exhibit the same remyelinating potential as the intact IgMs. The two antibodies displayed different structural requirements for retention of function. Antibody sHIgM22 remained functional even when reduced to a bivalent F(ab')2 fragment, while disruption of the pentameric structure of antibody 94.03 destroyed its functional properties. Competition studies demonstrated that the two antibodies recognize different entities on the surface of glial cells. These results indicate that the constant region and pentameric structure of IgM is not always necessary for the stimulation of myelin repair, eliminating the requirement for IgM immune effector functions in this process. The ability of the antibodies to cross-link cell surface determinants on oligodendrocytes appears to be an essential aspect of the mechanism of cellular activation. The finding that two antibodies, which induce similar in vivo effects, bind to different structures, and have different cross-linking requirements suggests that activation of glial cells involves the rearrangement of a complex membrane compartment.