scholarly journals Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort

JIMD Reports ◽  
2020 ◽  
Author(s):  
Stefanie Beck‐Wödl ◽  
Christiane Kehrer ◽  
Klaus Harzer ◽  
Tobias B. Haack ◽  
Friederike Bürger ◽  
...  
Keyword(s):  
Metachromatic Leukodystrophy ◽  
Disease Course ◽  
Multiple Sulfatase Deficiency

scholarly journals Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

2021 ◽  
pp. 1-3
Author(s):  
Sara Santos ◽  
Verónica Gamelas ◽  
Rita Saraiva ◽  
Guilherme Simões ◽  
Joana Saiote ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Improvement ◽  
Rescue Therapy ◽  
New Drugs ◽  
Multiple Drug ◽  
Disease Course ◽  
Efficacy And Safety ◽  
Severe Ulcerative Colitis ◽  
Rapid Absorption

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

scholarly journals Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice

2021 ◽  
Vol 14 ◽  
Author(s):  
Emilie Audouard ◽  
Valentin Oger ◽  
Béatrix Meha ◽  
Nathalie Cartier ◽  
Caroline Sevin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Gene Therapy ◽  
Metachromatic Leukodystrophy ◽  
Early Death ◽  
Lysosomal Storage ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Brain And Spinal Cord ◽  
Sulfatide Accumulation

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in both glial cells and neurons. MLD results from an inherited deficiency of arylsulfatase A (ARSA) and myelin degeneration in the central and peripheral nervous systems. Currently, no effective treatment is available for the most frequent late infantile (LI) form of MLD after symptom onset. The LI form results in rapid neurological degradation and early death. ARSA enzyme must be rapidly and efficiently delivered to brain and spinal cord oligodendrocytes of patients with LI MLD in order to potentially stop the progression of the disease. We previously showed that brain gene therapy with adeno-associated virus serotype rh10 (AAVrh10) driving the expression of human ARSA cDNA alleviated most long-term disease manifestations in MLD mice but was not sufficient in MLD patient to improve disease progression. Herein, we evaluated the short-term effects of intravenous AAVPHP.eB delivery driving the expression of human ARSA cDNA under the control of the cytomegalovirus/b-actin hybrid (CAG) promoter in 6-month-old MLD mice that already show marked sulfatide accumulation and brain pathology. Within 3 months, a single intravenous injection of AAVPHP.eB-hARSA-HA resulted in correction of brain and spinal cord sulfatide storage, and improvement of astrogliosis and microgliosis in brain and spinal cord of treated animals. These results strongly support to consider the use of AAVPHP.eB-hARSA vector for intravenous gene therapy in symptomatic rapidly progressing forms of MLD.

Objawy oczne w przebiegu chorób tarczycy

2018 ◽  
Vol 21 (1A) ◽  
Author(s):  
Paweł Wójtowiec ◽  
Anna Wójtowiec ◽  
Tomasz Tomkalski
Keyword(s):  
Severe Disease ◽  
Surgical Decompression ◽  
Clinical Activity ◽  
Graves Disease ◽  
Disease Course ◽  
Clinical Activity Score ◽  
Ocular Manifestations ◽  
Ocular Lesions ◽  
Degree Of Severity

Thyroid-related ocular manifestations are typically associated with Graves’ disease. The cause of Graves’ ophthalmopathy is not fully understood but it is believed to be autoimmune in origin. The most important risk factors are smoking and age. Patient’s gender also plays a significant role: ophthalmopathy is more prevalent in women but men experience a more severe disease course. There are two forms of the disease: inflammatory with congestion and pain in the eyeballs and fibrotic stage with impaired eye movements and no signs of inflammation. The degree of severity of ocular lesions is determined by NO SPECS classification and activity coefficient of orbitopathy (Clinical Activity Score – CAS). Previous clinical trials have not produced satysfying answers to questions about effective treatment of orbitopathy. In order to obtain the desired results it is to first necessary to achieve euthyroidism. Treatment is usually continual and long-term. Regimens in various centers vary, depending on their experiences. Currently the most commonly used are steroid therapy, radiation therapy and surgical decompression of the eye sockets. Surgical treatment is, however, used infrequently.

THU0400 CLINICAL COURSE OF EARLY AXIAL SPONDYLOARTHRITIS OVER TEN YEARS: LONG-TERM RESULTS FROM THE GERMAN SPONDYLOARTHRITIS INCEPTION COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 437-437
Author(s):  
D. Poddubnyy ◽  
V. Rios Rodriguez ◽  
M. Torgutalp ◽  
M. Verba ◽  
J. Callhoff ◽  
...  
Keyword(s):  
Disease Activity ◽  
Axial Spondyloarthritis ◽  
Clinical Course ◽  
Symptom Duration ◽  
Disease Course ◽  
Inception Cohort ◽  
Research Support ◽  
Low Disease Activity ◽  
Similar Disease

Background:Previous studies showed that patients with non-radiographic and radiographic axial spondyloarthritis (nr- and r-axSpA) have similar disease burden and similar response to anti-inflammatory therapy given similar level of inflammatory activity. Only little is known, however, about long-term disease course in patients with early axSpA.Objectives:To investigate the long-term (up to 10 years) clinical course of patients with early axSpA.Methods:In total, 525 patients with early axSpA (r-axSpA with symptom duration ≤10 years and nr-axSpA with symptom duration ≤5 years) from the German Spondyloarthritis Inception Cohort (GESPIC) were included. The final patient classification was based on central reading results in 458 patients with available pelvic X-rays, and on local rheumatologist judgement in 67 patients. A total of 251 patients were finally classified as r-axSpA and 274 as nr-axSpA. Clinical evaluation, which included disease activity (BASDAI, C-reactive protein – CRP, ASDAS) as well as therapy recording, was performed at baseline and every 6 months thereafter until year 2 and annually thereafter till year 10. Treatment was conducted at the discretion of the local rheumatologist.Results:Since the cohort has started prior to introduction of TNF inhibitors (TNFi), only 2% patients received TNFi at baseline that increased to 23% at year 10 (15% in nr-axSpA and 31% in r-axSpA) – Figure 1. The use of NSAIDs and csDMARDs decreased in both groups (Figure 1), while use of systemic steroids did not change substantially (9% at baseline, 8% at year 10). The proportion of patients with low disease activity according to BASDAI (<4) was higher in r-axSpA as compared to nr-axSpA at almost all time points, while the proportion of patients with low disease activity according to ASDAS (<2.1), as well as with ASDAS inactive disease (<1.3) was similar between nr-axSpA and r-axSpA (Figure 2). In the group of patients who completed year 10 (n=134 in total, 68 with nr-axSpA, 67 with r-axSpA) the same trends in therapy and disease activity were observed.Conclusion:Patients with nr-axSpA and r-axSpA showed a similar disease course in terms of disease activity on the group level. The drop-out rate in this observational cohort was overall high, but comparable between groups. The lower proportion of patients with nr-axSpA being treated with TNFi might reflect a later introduction of TNFi for this indication.Acknowledgments:GESPIC has been financially supported by the German Federal Ministry of Education and Research as well as by Abbott, Amgen, Centocor, Schering–Plough, and Wyeth. From 2010 till 2019 GESPIC has been supported by Abbvie.Disclosure of Interests:Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Valeria Rios Rodriguez Consultant of: Abbvie, Novartis, Murat Torgutalp: None declared, Maryna Verba: None declared, Johanna Callhoff: None declared, Mikhail Protopopov Consultant of: Novartis, Fabian Proft Grant/research support from: Novartis Pharma GmbH, Consultant of: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: Consultancy / speaker fees from: Abbvie, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Judith Rademacher: None declared, Hildrun Haibel Consultant of: Abbvie, Jansen, MSD, and Novartis, Speakers bureau: Abbvie, Jansen, MSD, and Novartis, Joachim Sieper Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Speakers bureau: AbbVie, Boehringer Ingelheim, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, and UCB Pharma, Martin Rudwaleit Consultant of: AbbVie, BMS, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB Pharma

scholarly journals Biomarker Application for Precision Medicine in Stroke

2019 ◽  
Vol 11 (4) ◽  
pp. 615-627 ◽  
Author(s):  
Alexis N. Simpkins ◽  
Miroslaw Janowski ◽  
Helieh S. Oz ◽  
Jill Roberts ◽  
Gregory Bix ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Hemorrhagic Stroke ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Stroke Survivor ◽  
Lifestyle Factors ◽  
Stroke Recovery ◽  
Therapeutic Interventions ◽  
Disease Course ◽  
Comprehensive Review

AbstractStroke remains one of the leading causes of long-term disability and mortality despite recent advances in acute thrombolytic therapies. In fact, the global lifetime risk of stroke in adults over the age of 25 is approximately 25%, with 24.9 million cases of ischemic stroke and 18.7 million cases of hemorrhagic stroke reported in 2015. One of the main challenges in developing effective new acute therapeutics and enhanced long-term interventions for stroke recovery is the heterogeneity of stroke, including etiology, comorbidities, and lifestyle factors that uniquely affect each individual stroke survivor. In this comprehensive review, we propose that future biomarker studies can be designed to support precision medicine therapeutic interventions after stroke. The current challenges in defining ideal biomarkers for stroke are highlighted, including consideration of disease course, age, lifestyle factors, and subtypes of stroke. This overview of current clinical trials includes biomarker collection, and concludes with an example of biomarker design for aneurysmal subarachnoid hemorrhage. With the advent of “-omics” studies, neuroimaging, big data, and precision medicine, well-designed stroke biomarker trials will greatly advance the treatment of a disease that affects millions globally every year.

scholarly journals Faecal Microbiota Dynamics and their Relation to Disease Course in Crohn’s Disease

2019 ◽  
Vol 13 (10) ◽  
pp. 1273-1282 ◽  
Author(s):  
Gianluca Galazzo ◽  
Danyta I Tedjo ◽  
Dion S J Wintjens ◽  
Paul H M Savelkoul ◽  
Ad A M Masclee ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Community Structure ◽  
Microbial Community ◽  
Disease Activity ◽  
Microbial Community Structure ◽  
Disease Course ◽  
Microbiota Composition ◽  
Faecal Microbiota ◽  
Over Time

Abstract Background Microbial shifts have been associated with disease activity in Crohn’s disease [CD], but findings on specific taxa are inconsistent. This may be due to differences in applied methods and cross-sectional study designs. We prospectively examined the faecal microbiota in adult CD patients with changing or stable disease course over time. Methods Faeces were collected at two time-points from 15 healthy control individuals [HCs], 35 CD patients who were in remission and who maintained remission [RRs], and 22 CD patients during remission and also during subsequent exacerbation [RAs]. The microbial composition was assessed by 16S rRNA [V4] gene sequencing. Results Compared with HCs, patients with CD had a lower microbial richness [p = 0.0002] and diversity [p = 0.005]. Moreover, the microbial community structure of a subset of patients, clustered apart from HCs, was characterized by low microbial diversity and Faecalibacterium abundance. Patients within this cluster did not differ with respect to long-term disease course compared with patients with a ‘healthy-appearing’ microbiota. Over time, microbial richness and diversity did not change in RR versus RA patients. Although the microbial community structure of both RR and RA patients was less stable over time compared with that of HCs, no differences were observed between the patient groups [p = 0.17]; nor was the stability impacted by Montreal classification, medication use, or surgery. Conclusion The altered microbiota composition and stability in CD was neither associated with disease activity nor long-term disease course, questioning its involvement in the development of an exacerbation. The aberrant microbiota composition in a subset of CD patients warrants further exploration of a more microbiota-driven etiology in this group.

scholarly journals Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis: part 1—results of the Canadian model in the Nordic cohort

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Veronika Rypdal ◽  
◽  
Jaime Guzman ◽  
Andrew Henrey ◽  
Thomas Loughin ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Prediction Model ◽  
Prediction Models ◽  
Severe Disease ◽  
Disease Onset ◽  
Fine Tuning ◽  
Disease Course ◽  
Internal Validation ◽  
Long Term Outcome

Abstract Background Models to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA. Methods The Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction. Results The Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83–0.87) for prediction of severe disease course and a C-index of 0.66 (0.63–0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80–0.89) and 0.69 (0.65–0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86–0.92). Conclusions External validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.

scholarly journals Small Fibre Involvement in Multifocal Motor Neuropathy Explored with Sudoscan: A Single-Centre Experience

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 755
Author(s):  
Marco Luigetti ◽  
Silvia Giovannini ◽  
Angela Romano ◽  
Giulia Bisogni ◽  
Francesco Barbato ◽  
...  
Keyword(s):  
Sensory Nerve ◽  
Multifocal Motor Neuropathy ◽  
Motor Neuropathy ◽  
Disease Course ◽  
Small Fibre ◽  
Single Centre Experience ◽  
Inflammatory Neuropathy ◽  
Sensory Nerve Action ◽  
Neurophysiological Data

Objective: Multifocal motor neuropathy (MMN) is a rare inflammatory neuropathy, clinically characterized by exclusive motor involvement. We wished to evaluate the possible presence of sensory dysfunction, including the evaluation of small fibres, after a long-term disease course. Patients and methods: seven MMN patients, regularly followed in our Neurology Department, underwent clinical evaluation, neurophysiological examination by nerve conduction studies (NCSs), and Sudoscan. We compared neurophysiological data with a group of patients with other disorders of the peripheral nervous system. Results: NCSs showed a reduction of sensory nerve action potential amplitude in 2/7 MMN patients. Sudoscan showed borderline electrochemical skin conductance (ESC) values in 3/7 MMN patients (two of them with abnormal sensory NCSs). Conclusions: Our results confirm that sensory involvement may be found in some MMN after a long-term disease course, and it could also involve the small fibres.

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