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Treatment of Vasculitis of the Nervous System

Younger, David S
The diagnosis of primary central and peripheral nerve vasculitides should be established with certainty if suspected before commencing potent immunosuppressive therapy. The aim of induction therapy is to rapidly control the underlying inflammatory response and stabilize the blood-brain and blood-nerve barriers, followed by maintenance immunosuppression tailored to the likeliest humoral and cell-mediated autoimmune inflammatory vasculitic processes.
PMID: 30952416
ISSN: 1557-9875
CID: 3898192

Clinical characteristics of patients presenting with minor stroke: A single center, one-year retrospective observational study [Meeting Abstract]

Mirasol, R; Golub, D; Balcer, L; Serrano, L; Ishida, K; Favate, A
Background and Aims: Contemplating the use of N-acetylcysteine as a neuroprotectant, with dextran as an antithrombotic for patients with NIHSS less than or equal to 5, we quantified treatment-relevant clinical characteristics of a sample of this patient population at a single stroke center over one year.
Method(s): Patients with NIHSSResult(s): One-hundred twenty-eight of 310 (41%) patients with ischemic stroke had NIHSSConclusion(s): Minor stroke symptoms may not be captured by the current NIHSS. This population rarely had renal or hepatic failure, making them good candidates for combination N-acetylcysteine and dextran
EMBASE:628560907
ISSN: 2396-9881
CID: 4001212

Dermatologic Aspects of Systemic Vasculitis

Younger, David S; Carlson, Andrew
Systemic and localized vasculitis affects the skin and subcutis, due to large vascular beds and hemodynamic factors, such as stasis in lower extremities, and environmental influences, as occur in cold exposure. Initial cutaneous manifestations of vasculitides include diverse and dynamic patterns of discoloration, swelling, hemorrhage, and necrosis. One-half of affected patients present with localized, self-limited disease to the skin without any known trigger or associated systemic disease, known as idiopathic cutaneous leukocytoclastic vasculitis. Skin biopsy and dermatopathology contribute relevant information; however, they require correlation with clinical history, physical examination, and laboratory findings to reach an accurate diagnosis.
PMID: 30952419
ISSN: 1557-9875
CID: 3789762

Effect of Red Yeast Rice on Cognitive Functioning in Schizophrenia: Data From a Pilot Study

Bruno, Antonio; Pandolfo, Gianluca; Crucitti, Manuela; Troili, Giulia Maria; Battaglia, Fortunato; Zoccali, Rocco Antonio; Muscatello, Maria Rosaria Anna
BACKGROUND:Cognitive deficits (CDs) in schizophrenia affect poor outcome and real-world community functioning. Because redox imbalance has been implicated, among other factors, in the pathophysiology of CDs, antioxidant compounds may have a beneficial effect in their treatment. Red yeast rice (RYR), besides its lipid-lowering effect, exhibit antioxidant and anti-inflammatory. METHODS:Thirty-five schizophrenia outpatients (age range, 18-60 years) on stable antipsychotic treatment and assessed by neuropsychological (Wisconsin Card Sorting Test [WCST], Verbal Fluency, and Stroop task) and psychodiagnostic instruments (Brief Psychiatric Rating Scale) received RYR at daily dosage of 200 mg/d (total monacolin K/capsule content, 11.88 mg) for 12 weeks. RESULTS:Red yeast rice supplementation significantly improved WCST "perseverative errors" (P = 0.015), "total errors" (P = 0.017, P = 0.001), and phonemic fluency test (P = 0.008); a trend for improvement on other WCST variables ("nonperseverative errors," "perseverative responses," and "categories") was observed. Effect sizes, according to Cohen's suggestions, were small in all explored cognitive dimensions. There were no significant change in clinical symptoms and no subject-reported adverse effects. CONCLUSIONS:Despite several limitations (open design, lack of a control group, short period of observation, small sample size, mode of controlling patients' compliance, the lack of assessment of patients' functional improvement), results suggest that RYR supplementation may be a potentially promising strategy for addressing CDs in schizophrenia; further randomized, placebo-controlled studies are needed to better evaluate the potential role of RYR for the treatment of CDs in schizophrenia.
PMID: 30921099
ISSN: 1533-712x
CID: 3777372

Central Nervous System Vasculitis Due to Substance Abuse

Younger, David S
Illicit drug abuse is a common differential diagnosis of acquired central nervous system vasculitis even though there are only a handful of histopathologically confirmed patients in the literature from among the many potential classes of abused drugs traditionally implicated in this disease. This article considers the major classes of illicit drugs in those with and without human immunodeficiency virus type-1 infection and acquired immune deficiency syndrome.
PMID: 30952417
ISSN: 1557-9875
CID: 3789752

Overview of the Vasculitides

Younger, David S
The systemic vasculitides are heterogeneous clinicopathologic disorders that share the common feature of vascular inflammation. The resulting disorder can vary depending on involvement of specific organs, caliber of blood vessels, the underlying inflammatory process, and individual host factors. The cumulative result is diminished blood flow, vascular alterations, and eventual occlusion with variable ischemia, necrosis, and tissue damage. An international revised nomenclature system provides the necessary nosology and findings relevant to classify each of the vasculitides. This article is an introduction and overview of the clinical presentation, differential diagnosis, laboratory evaluation, and treatment of systemic and nervous system vasculitides.
PMID: 30952404
ISSN: 1557-9875
CID: 3789572

Granulomatous Angiitis: Twenty Years Later

Younger, David S
Granulomatous inflammation, the prototypical histopathology of adult and childhood vasculitis, is characterized by inflammation of blood vessels accompanied by giant cells and epithelioid cells in the walls of cerebral vessels ranging from small leptomeningeal veins to large named cerebral arteries. Headache, hemiparesis, mental changes, abnormal cerebrospinal fluid protein content, and pleocytosis are suggestive features that warrant brain and leptomeningeal biopsy to make the diagnosis certain and begin cytotoxic therapy to improve outcome.
PMID: 30952409
ISSN: 1557-9875
CID: 3789582

Depression and all-cause mortality risk in HIV-infected and HIV-uninfected US veterans: a cohort study

So-Armah, K; Gupta, S K; Kundu, S; Stewart, J C; Goulet, J L; Butt, A A; Sico, J J; Marconi, V C; Crystal, S; Rodriguez-Barradas, M C; Budoff, M; Gibert, C L; Chang, C-Ch; Bedimo, R; Freiberg, M S
OBJECTIVES/OBJECTIVE:The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. METHODS:Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. RESULTS:Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. CONCLUSIONS:Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment.
PMID: 30924577
ISSN: 1468-1293
CID: 3795302

Epidemiology of the Vasculitides

Younger, David S
The epidemiology of vasculitis has witnessed extraordinary advances in the past decade influenced by the worldwide increased recognition and accurate classification and diagnosis of the vasculitides, and insights brought by genome-wide association studies and online genetic biological repositories that permit researchers to freely access a wide array of genetic and clinical resources that contribute to the understanding of the heritable factors of the systemic vasculitides. This article reviews the current knowledge of the epidemiology of vasculitides in different global regions.
PMID: 30952405
ISSN: 1557-9875
CID: 3898182

Modeling visual performance differences 'around' the visual field: A computational observer approach

Kupers, Eline R; Carrasco, Marisa; Winawer, Jonathan
Visual performance depends on polar angle, even when eccentricity is held constant; on many psychophysical tasks observers perform best when stimuli are presented on the horizontal meridian, worst on the upper vertical, and intermediate on the lower vertical meridian. This variation in performance 'around' the visual field can be as pronounced as that of doubling the stimulus eccentricity. The causes of these asymmetries in performance are largely unknown. Some factors in the eye, e.g. cone density, are positively correlated with the reported variations in visual performance with polar angle. However, the question remains whether these correlations can quantitatively explain the perceptual differences observed 'around' the visual field. To investigate the extent to which the earliest stages of vision-optical quality and cone density-contribute to performance differences with polar angle, we created a computational observer model. The model uses the open-source software package ISETBIO to simulate an orientation discrimination task for which visual performance differs with polar angle. The model starts from the photons emitted by a display, which pass through simulated human optics with fixational eye movements, followed by cone isomerizations in the retina. Finally, we classify stimulus orientation using a support vector machine to learn a linear classifier on the photon absorptions. To account for the 30% increase in contrast thresholds for upper vertical compared to horizontal meridian, as observed psychophysically on the same task, our computational observer model would require either an increase of ~7 diopters of defocus or a reduction of 500% in cone density. These values far exceed the actual variations as a function of polar angle observed in human eyes. Therefore, we conclude that these factors in the eye only account for a small fraction of differences in visual performance with polar angle. Substantial additional asymmetries must arise in later retinal and/or cortical processing.
PMCID:6553792
PMID: 31125331
ISSN: 1553-7358
CID: 4029692