Impact of Focal White Matter Damage on Localized Subcortical Gray Matter Atrophy in Multiple Sclerosis: A 5-Year Study.

Background And Purpose: It is unclear to what extent subcortical gray matter atrophy is a primary process as opposed to a result of focal white matter damage. Correlations between WM damage and atrophy of subcortical gray matter have been observed but may be partly attributable to indirect relationships between co-occurring processes arising from a common cause. Our aim was to cross-sectionally and longitudinally characterize the unique impact of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression.

Hospital length of stay variation and comorbidity of mental illness: a retrospective study of five common chronic medical conditions.

Background: With the increasing burden of mental illness globally, it is becoming common for hospitalised patients with chronic medical conditions to have a comorbidity of mental illness. This combination could prolong length of stay (LOS) of this patient cohort. We conducted an investigation in Tasmania, Australian hospitals to characterise this cohort and assess if co-morbidity of mental illness is a distinguishing factor that generates LOS variation across different chronic medical conditions.

Thalamic white matter in multiple sclerosis: A combined diffusion-tensor imaging and quantitative susceptibility mapping study.

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty-five MS patients and 17 demographically-matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility.

Laboratory Tests for Diagnosis of Chronic Periprosthetic Joint Infection Can Help Predict Outcomes of Two-Stage Exchange.

Background: Although 2-stage exchange arthroplasty is the most effective treatment among available strategies for managing chronic periprosthetic joint infection (PJI), rates of its success vary greatly. The purpose of our study was to examine whether objective measurements collected at the time of the diagnosis of PJI could be used to identify patients at risk of failure of 2-stage exchange.

Methods: We identified 205 patients across 4 institutions who underwent 2-stage exchange arthroplasty for the treatment of PJI following total hip or total knee arthroplasty.

Atrophied Brain Lesion Volume: A New Imaging Biomarker in Multiple Sclerosis.

Background And Purpose: Lesion accrual in multiple sclerosis (MS) is an important and clinically relevant measure, used extensively as an imaging trial endpoint. However, lesions may also shrink or disappear entirely due to atrophy. Although generally ignored or treated as a nuisance, this phenomenon may actually be an important stand-alone imaging biomarker.

Fingolimod's Impact on MRI Brain Volume Measures in Multiple Sclerosis: Results from MS-MRIUS.

Background And Purpose: Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD).

Methods: MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months.

White matter tract network disruption explains reduced conscientiousness in multiple sclerosis.

Quantifying white matter (WM) tract disruption in people with multiple sclerosis (PwMS) provides a novel means for investigating the relationship between defective network connectivity and clinical markers. PwMS exhibit perturbations in personality, where decreased Conscientiousness is particularly prominent. This trait deficit influences disease trajectory and functional outcomes such as work capacity.

MK-8325: A silyl proline-containing NS5A inhibitor with pan-genotype activity for treatment of HCV.

HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination regimen. Herein, we describe the discovery and characterization of silyl proline-containing HCV NS5A inhibitor MK-8325 with good pan-genotype activity and acceptable pharmacokinetic properties.

Establishing pathological cut-offs for lateral ventricular volume expansion rates.

Background: A percent brain volume change (PBVC) cut-off of -0.4% per year has been proposed to distinguish between pathological and physiological changes in multiple sclerosis (MS). Unfortunately, standardized PBVC measurement is not always feasible on scans acquired outside research studies or academic centers.

The Role of High-Frequency MRI Monitoring in the Detection of Brain Atrophy in Multiple Sclerosis.

Background And Purpose: A relatively high intraindividual variability of longitudinal magnetic resonance imaging (MRI) of brain volume loss (BVL) measurements over time renders challenging its application to individual multiple sclerosis (MS) patients. Objective of this study was to investigate if high-frequency brain MRI monitoring affects identification of pathological BVL in an individual patient.

Methods: One hundred fifty-seven relapsing-remitting MS patients had seven MRI scans over 12 months follow-up.

Age and sex differences in behavioral flexibility, sensitivity to reward value, and risky decision-making.

Compared with adults, adolescent behavior is often characterized by reduced behavioral flexibility, increased sensitivity to reward, and increased likelihood to take risks. These traits, which have been hypothesized to confer heightened vulnerability to psychopathologies such as substance use disorders (SUDs), have been the focus of studies in laboratory animal models that seek to understand their neural underpinnings. However, rodent studies to date have typically used only males and have adopted standard methodological practices (e.

NCCN Guidelines Insights: T-Cell Lymphomas, Version 2.2018.

Natural killer (NK)/T-cell lymphomas are a rare and distinct subtype of non-Hodgkin's lymphomas. NK/T-cell lymphomas are predominantly extranodal and most of these are nasal type, often localized to the upper aerodigestive tract. Because extranodal NK/T-cell lymphomas (ENKL) are rare malignancies, randomized trials comparing different regimens have not been conducted to date and standard therapy has not yet been established for these patients.

Evaluation of Leptomeningeal Contrast Enhancement Using Pre-and Postcontrast Subtraction 3D-FLAIR Imaging in Multiple Sclerosis.

Background And Purpose: Leptomeningeal contrast enhancement is found in patients with multiple sclerosis, though reported rates have varied. The use of 3D-fluid-attenuated inversion recovery pre- and postcontrast subtraction imaging may more accurately determine the frequency of leptomeningeal contrast enhancement. The purpose of this study was to investigate the frequency of leptomeningeal contrast enhancement using the pre- and postcontrast subtraction approach and to evaluate 3 different methods of assessing the presence of leptomeningeal contrast enhancement.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial.

Objectives: The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging.

Background: TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease.

Evidence of progressive tissue loss in the core of chronic MS lesions: A longitudinal DTI study.

Objective: Using diffusion tensor imaging (DTI), we examined chronic stable MS lesions, peri-lesional white matter (PLWM) and normal appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (RRMS) for evidence of progressive tissue destruction and evaluated whether diffusivity change is associated with conventional MRI parameters and clinical findings.

Method: Pre- and post-gadolinium T1, T2 and DTI images were acquired from 55 consecutive RRMS patients at baseline and 42.3 ± 9.

Longitudinal personality change associated with cognitive decline in multiple sclerosis.

We previously reported that personality and cognition were stable over 3 years in patients with multiple sclerosis (MS). This study examined whether a longer duration would reveal evidence of emerging personality dysfunction. The NEO Five-Factor Inventory and Brief International Cognitive Assessment for MS was used to assess personality and cognition, respectively.

Verbal Learning and Memory in Cannabis and Alcohol Users: An Event-Related Potential Investigation.

Long-term heavy use of cannabis and alcohol are known to be associated with memory impairments. In this study, we used event-related potentials to examine verbal learning and memory processing in a commonly used behavioral task. We conducted two studies: first, a small pilot study of adolescent males, comprising 13 Drug-Naive Controls (DNC), 12 heavy drinkers (HD) and 8 cannabis users (CU).

Progressive inner nuclear layer dysfunction in non-optic neuritis eyes in MS.

Objective: To investigate primary retinal functional changes in non-optic neuritis (ON) eyes of patients with MS by full-field electroretinography (ERG).

Methods: Seventy-seven patients with relapsing-remitting MS with no history of clinical ON in at least 1 eye and 30 healthy controls were recruited in the cohort study. Full-field ERGs were recorded, and retinal optical coherence tomography scans were performed to assess the thicknesses of peripapillary retinal nerve fiber layer (RNFL) and retinal ganglion cell layer-inner plexiform layer (GCL-IPL).

Design and Synthesis of Piperazine Sulfonamide Cores Leading to Highly Potent HIV-1 Protease Inhibitors.

Using the HIV-1 protease binding mode of and as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to .

NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 3.2017.

The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the management of patients with high-risk syndromes associated with an increased risk of colorectal cancer (CRC). The NCCN Panel for Genetic/Familial High-Risk Assessment: Colorectal meets at least annually to assess comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights focus on genes newly associated with CRC risk on multigene panels, the associated evidence, and currently recommended management strategies.

Design and Operation of the Transformed National Healthy Start Evaluation.

Purpose Improving pregnancy outcomes for women and children is one of the nation's top priorities. The Healthy Start (HS) program was created to address factors that contribute to high infant mortality rates (IMRs) and persistent disparities in IMRs. The program began in 1991 and was transformed in 2014 to apply lessons from emerging research, past evaluation findings, and expert recommendations.

Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals.

Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3 T MRI examination.

Feasibility of Brain Atrophy Measurement in Clinical Routine without Prior Standardization of the MRI Protocol: Results from MS-MRIUS, a Longitudinal Observational, Multicenter Real-World Outcome Study in Patients with Relapsing-Remitting MS.

Background And Purpose: Feasibility of brain atrophy measurement in patients with MS in clinical routine, without prior standardization of the MRI protocol, is unknown. Our aim was to investigate the feasibility of brain atrophy measurement in patients with MS in clinical routine.

Materials And Methods: Multiple clerosis and Clinical Outcome and MR Imaging in the United States (MS-MRIUS) is a multicenter (33 sites), retrospective study that included patients with relapsing-remitting MS who began treatment with fingolimod.

Gray matter atrophy patterns in multiple sclerosis: A 10-year source-based morphometry study.

Objectives: To investigate spatial patterns of gray matter (GM) atrophy and their association with disability progression in patients with early relapsing-remitting multiple sclerosis (MS) in a longitudinal setting.

Methods: Brain MRI and clinical neurological assessments were obtained in 152 MS patients at baseline and after 10 years of follow-up. Patients were classified into those with confirmed disability progression (CDP) ( = 85) and those without CDP ( = 67) at the end of the study.