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Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients
ObjectiveTo report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies.MethodsFrom January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients’ serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections.ResultsSerum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells.ConclusionsGFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.
Journal Article
Quiet your mind & get to sleep : solutions to insomnia for those with depression, anxiety, or chronic pain
For people with insomnia and often comorbid disorders such as depression, anxiety, and chronic pain, this book has methods from cognitive behavioral therapy for getting the sleep they need and improving their symptoms in the process.
Book
Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study
ObjectivesThe impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness.MethodsIn this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression.ResultsThe cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53–78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30).ConclusionIn hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.
Journal Article
The Hyperglycemia and Adverse Pregnancy Outcome Study: Associations of GDM and obesity with pregnancy outcomes
To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.
Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes.
Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m(2)), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93-2.47), for obesity alone 1.73 (1.50-2.00), and for both GDM and obesity 3.62 (3.04-4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women).
Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.
Journal Article
Systematic unenhanced CT for acute abdominal symptoms in the elderly patients improves both emergency department diagnosis and prompt clinical management
Objectives
To assess the added-value of systematic unenhanced abdominal computed tomography (CT) on emergency department (ED) diagnosis and management accuracy compared to current practice, in elderly patients with non-traumatic acute abdominal symptoms.
Methods
Institutional review board approval and informed consent were obtained. This prospective study included 401 consecutive patients 75 years of age or older, admitted to the ED with acute abdominal symptoms, and investigated by early systematic unenhanced abdominal CT scan. ED diagnosis and intended management before CT, after unenhanced CT, and after contrast CT if requested, were recorded. Diagnosis and management accuracies were evaluated and compared before CT (clinical strategy) and for two conditional strategies (current practice and systematic unenhanced CT). An expert clinical panel assigned a final diagnosis and management after a 3-month follow-up.
Results
Systematic unenhanced CT significantly improved the accurate diagnosis (76.8% to 85%,
p
=1.1x10
-6
) and management (88.5% to 95.8%,
p
=2.6x10
-6
) rates compared to current practice. It allowed diagnosing 30.3% of acute unsuspected pathologies, 3.4% of which were unexpected surgical procedure requirement.
Conclusions
Systematic unenhanced abdominal CT improves ED diagnosis accuracy and appropriate management in elderly patients presenting with acute abdominal symptoms compared to current practice.
Key Points
•
Systematic unenhanced CT improves significantly diagnosis accuracy compared to current practice.
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Systematic unenhanced CT optimizes appropriate hospitalization by increasing the number of discharged patients.
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Systematic unenhanced CT allows detection of about one-third of acute unsuspected abdominal conditions.
•
It should allow boosting emergency department management decision-making confidence in old patients.
Journal Article
REM sleep behaviour disorder in patients without synucleinopathy
Cases of subclinical RBD (defined as confirmed REM sleep without atonia in the absence of RBD symptoms), cognitive impairment or neurological presentations of uncertain aetiology, or RBD occurring in healthy individuals (usually children) were excluded. The importance of the brainstem location, as opposed to the underlying disease mechanism, was further highlighted by co-occurrence of RBD and Arnold-Chiari malformations in 29 patients (12%).Table 1 Non-synuclein pathologies associated with RBD Condition Number of patients Subcategory Supplementary References Structural brain lesion 45 Ischaemic (n=23)*, multiple sclerosis (n=7), indeterminate lesion (n=4), meningioma (n=3), adult-onset leukodystrophy (n=2), post-operative following brain surgery (n=1), brainstem cavernoma (n=1), aneurysm (n=1), brainstem lymphoma (n=1), astrocytoma (n=1), anoxic encephalopathy (n=1) 1,2, 3†, 4†,5,6, 7‡, 8-12, 13§, 14, 15, 16¶, 17-21 Arnold-Chiari malformation 29 Type 1 (n=6), Type II (n=23) 22,23 Alzheimer’s disease 29 na 13§, 24-31, 32§ Spinocerebellar ataxia 25 SCA-3 (n=20), SCA of uncertain aetiology (n=4), SCA-31 (n=1) 30, 33-38 Autoimmune brain disease 22 Voltage-gated potassium channel antibody encephalitis (n=9), paediatric acute-onset neuropsychiatric syndrome (n=4), anti-Ma antibody encephalitis (n=3), encephalitis of uncertain aetiology (n=3), paraneoplastic cerebellar degeneration (n=2), NMDA receptor encephalitis (n=1) 6, 13§, 16¶, 39-42, 43§, 44, 45, 46 Epilepsy 19 na 15, 47-49 Progressive supranuclear palsy 15 na 6, 13§, 50, 51, 52§, 53 Traumatic brain injury 11 na 2, 3†, 54. Only conditions with five or more cases are shown, with the following conditions being observed less frequently: amyotrophic lateral sclerosis (n=4), dentatorubropallidoluysian atrophy (n=4), anti-IgLON5 disease (n=4), autism (n=4), Huntington’s disease (n=3), Creutzfeldt-Jakob disease (n=3), Mobius syndrome (n=2), Guillain-Barré syndrome (n=1), frontotemporal dementia (n=1), Tourette’s syndrome (n=1), myotonic dystrophy type 2 (n=1) and hereditary hyperekplexia (n=1). *Mainly involving the pons. †RBD occurred as part of parasomnia overlap syndrome. ‡Not located in the brainstem and one patient also had epilepsy. §Pathologically confirmed cases. ¶Two patients did not undergo polysomnography but insufficient information from paper to confirm which ones. **This is a form of tauopathy. na, not applicable; RBD, REM sleep behaviour disorder; SCA, spinocerebellar ataxia.
Journal Article