scholarly journals Immunomodulation with Azathioprine therapy in Rasmussen syndrome: A multimodal evaluation

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011004
Author(s):  
Serena Pellegrin ◽  
Torsten Baldeweg ◽  
Suresh Pujar ◽  
Felice D’Arco ◽  
Gaetano Cantalupo ◽  
...  

Objective:To verify safety and efficacy of the corticosteroid-sparing drug Azathioprine (AZA) in Rasmussen syndrome (RS), we retrospectively analyzed a cohort of RS patients recruited in a single pediatric neuroscience center.Methods:We compared outcomes in 30 RS patients who received AZA with 23 patients who were not treated with this drug. We used a multimodal approach to correlate therapy with clinical features (seizures, epilepsia partialis continua [EPC], hemiparesis) and neuroimaging markers of progressive brain atrophy.Results:AZA was well tolerated; only one patient discontinued treatment due to pancytopenia. In 27/30 AZA patients, all of whom were corticosteroid responders, corticosteroid therapy could be weaned or reduced without worsening of seizures in 89%. AZA patients had a lower prevalence of EPC (42% vs. 67% in controls) and hemiparesis (64% vs. 92%, respectively). Cox regression showed for the AZA group compared to controls a delayed time to: 1) EPC (of about 2 years, Exp(B)=0.295, 95%CI[0.108, 0.807];p=0.017), 2) hemiparesis (about one year, Exp(B)=0.315, 95%CI[0.137, 0.724];p=0.007), and 3) surgery (about 2 years, Exp(B)=2.068, 95%CI[1.012, 4.227];p=0.046). However, there were no group differences in cognitive decline over time (IQ change per year) or in hemispheric grey matter atrophy on serial MRI scans.Conclusion:AZA treatment appears to slow clinical progression of Rasmussen syndrome in steroid responders; this will give most advantage in patients in the early stages of the disease in whom surgical decision-making may require further time.Classification of Evidence:This study provides Class III evidence that for pediatric RS patients AZA is well tolerated and slows hemiparesis and appearance of EPC.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Domingo ◽  
L Conangla ◽  
J Lupon ◽  
M De Antonio ◽  
P Moliner ◽  
...  

Abstract Background The role of lung ultrasound (LUS) in diagnosis and response to diuretic treatment of patients with acute HF has been widely studied, but less is known about its value in chronic HF. Purpose To assess the prognostic value of LUS in a cohort of chronic HF stable ambulatory patients and to explore the relationship of LUS findings with clinical data, such as NYHA functional class, left ventricular ejection fraction (LVEF) and NTproBNP. Methods Consecutive stable ambulatory patients who attended a scheduled follow-up visit in a HF clinic were included. LUS were performed with a pocket device and examined 4 chest areas per side (two anterior and two lateral). Scans were analysed offline by two investigators blinded to clinical data, who evaluated the number of B-lines of each area. The addition number of B-lines of each area and the quartiles of such addition were used for the analyses. The primary outcome end-point was the composite of all-cause death or hospitalization due to HF at one year. Linear regression and Cox regression analyses were performed. Results Five-hundred seventy-seven patients were included between July 2016 and July 2017 (age 69±12 years, 72% men). The main HF aetiology was ischemic heart disease (43%) followed by dilated cardiomyopathy (20%). Median HF duration was 79 months (Q1-Q3 38–144). Mean LVEF was 45%±13 (mean LVEF when admitted at the Unit 34%±13). Most patients were in NYHA functional class II (70%), 13% were in class I and 17% in class III. Median NTproBNP was 722 ng/L (Q1-Q3 262–1760). Mean number of B-lines was 5±6 (Q1, 0; Q2, 1–3; Q3, 4–7; Q4, ≥8). The number of B-lines was associated with age (beta-coefficient 0.11, p<0.001), NYHA functional class (beta-coefficient 1.75, p<0.001), and logNTproBNP (beta-coefficient 1.40, p<0.001). Mean number of B-lines according to NYHA functional class was: class I, 3.5±6; class II, 4.9±6; and class III, 7.1±7. During the one year follow-up 47 patients suffered the primary end-point. In total there were 24 HF related hospitalizations and 26 deaths. In Cox regression analysis, Q4 of B-lines showed a double risk of suffering the primary end-point (HR 2.13 [95% CI 1.18–3.84], p=0.01). However, statistically significance was not maintained for LUS results in the multivariable analysis when age, NYHA functional class and logNTproBNP were included in the model, although a 38% increase in the risk of suffering the primary end-point for Q4 was observed (HR 1.38 [95% CI 0.75–2.54], p=0.31). Conclusion In outpatients with stable chronic HF, the number of B-lines detected in LUS was associated with age, NYHA functional class and NTproBNP. Patients having ≥8 B-lines had a significant double risk of HF related hospitalization or all-cause death at one year. However, when strongly powerful prognostic variables such as NYHA class and NTproBNP were included in the model LUS did not retain an independent prognostic role.


Neurology ◽  
2018 ◽  
Vol 90 (21) ◽  
pp. e1849-e1857 ◽  
Author(s):  
Joaquim J. Ferreira ◽  
Andrew J. Lees ◽  
Werner Poewe ◽  
Olivier Rascol ◽  
José-Francisco Rocha ◽  
...  

ObjectiveTo evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease.MethodsAfter completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments. The primary efficacy variable was the change from baseline in absolute “off” time based on patient diaries. Other outcomes included proportion of responders, scale-based assessments, and standard safety assessments.ResultsOne year of treatment with opicapone reduced “off” time by a half-hour (33.8 minutes) vs the open-label baseline and >2 hours (126.9 minutes) vs the double-blind baseline. Whereas patients who were originally treated with opicapone 50 mg in the double-blind phase maintained their efficacy, switching treatments led to further decreases in “off” time (−64.9, −39.3, −27.5, and −23.0 minutes for switching from placebo, entacapone, and opicapone 5 and 25 mg, respectively). Dyskinesia was the most frequently reported adverse event (14.5%) and was managed by adjustment of dopaminergic therapy. No new safety concerns were observed with long-term opicapone administration.ConclusionLong-term use of opicapone provided sustained efficacy over 1 year. Switching from entacapone to opicapone led to enhanced efficacy under the conditions of the study.Classification of evidenceThis study provides Class III evidence that for patients with Parkinson disease and end-of-dose motor fluctuations, long-term use (52 weeks) of opicapone is well tolerated and reduces “off” time.


2012 ◽  
Vol 107 (06) ◽  
pp. 1172-1179 ◽  
Author(s):  
Jonas Olesen ◽  
Christian Torp-Pedersen ◽  
Morten Hansen ◽  
Gregory Lip

SummaryNorth American and European guidelines on atrial fibrillation (AF) are conflicting regarding the classification of patients at low/intermediate risk of stroke. We aimed to investigate if the CHA2DS2-VASc score improved risk stratification of AF patients with a CHADS2 score of 0–1. Using individual-level-linkage of nationwide Danish registries 1997–2008, we identified patients discharged with AF having a CHADS2 score of 0–1 and not treated with vitamin K antagonist or heparin. In patients with a CHADS2 score of 0, 1, and 0–1, rates of stroke/ thromboembolism were determined according to CHA2DS2-VASc score, and the risk associated with increasing CHA2DS2-VASc score was estimated in Cox regression models adjusted for year of inclusion and anti-platelet therapy. The value of adding the extra CHA2DS2-VASc risk factors to the CHADS2 score was evaluated by c-statistics, Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). We included 47,576 patients with a CHADS2 score of 0–1, from these 7,536 (15.8%) were CHA2DS2-VASc score=0, 10,062 (21.2%) were CHA2DS2-VASc score=1, 14,310 (30.1%) were CHA2DS2-VASc score=2, 14,188 (29.8%) were CHA2DS2-VASc score=3, and 1,480 (3.1%) were CHA2DS2-VASc score=4. Of the cohort with a CHADS2 score of 0–1, the stroke/thromboembolism rate per 100 person-years increased with increasing CHA2DS2-VASc score (95% confidence interval): 0.84 (0.65–1.08), 1.79 (1.53–2.09), 3.67 (3.34–4.03), 5.75 (5.33–6.21), and 8.18 (6.68–10.02) at one year follow-up with CHA2DS2-VASc scores of 0, 1, 2, 3, and 4, respectively. Patients with a CHADS2 score=0 were not all ‘low risk’, with one-year event rates ranging from 0.84 (CHA2DS2-VASc score=0) to 3.2 (CHA2DS2-VASc score=3). Results from Cox regression analyses, NRI, and IDI confirmed the improved predictive ability of the CHA2DS2-VASc score in the AF patients who have a CHADS2 score of 0–1. In conclusion, the CHA2DS2-VASc provides critical information on risk of stroke in AF patients with a CHADS2 score of 0–1 that can aid a decision of using anti-coagulation. Even in patients categorised as ‘low risk’ using a CHADS2 score=0, the CHA2DS2-VASc score significantly improved the predictive value of the CHADS2 score alone and a CHA2DS2-VASc score=0 could clearly identify ‘truly low risk’ subjects. Use of the CHA2DS2-VASc score would significantly improve classification of AF patients at low and intermediate risk of stroke, compared to the commonly used CHADS2 score.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ulrich Jehn ◽  
Katharina Schütte-Nütgen ◽  
Ute Henke ◽  
Hermann Pavenstädt ◽  
Barbara Suwelack ◽  
...  

AbstractThe prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Marco Monticone ◽  
Igor Portoghese ◽  
Daniele Cazzaniga ◽  
Valentina Liquori ◽  
Giuseppe Marongiu ◽  
...  

Abstract Background General physiotherapy is a common means of rehabilitation after surgery for proximal humeral fracture (PHF). Better-targeted exercises seem worthy of investigation and the aim of this study was to assess the efficacy of a rehabilitation program including task-oriented exercises in improving disability, pain, and quality of life in patients after a PHF. Methods By means of a randomized controlled trial with one-year follow-up, 70 working patients (mean age of 49 ± 11 years; 41 females), who were selected for open reduction and internal fixation with plates caused by PHF, were randomized to be included in an experimental (n = 35) or control group (n = 35). There was a permuted-block randomization plan, and a list of program codes was previously created; subsequently, an automatic assignment system was used to conceal the allocation. The first group underwent a supervised rehabilitation program of task-oriented exercises based on patients’ specific job activities, and occupational therapy. The second group underwent general physiotherapy, including supervised mobility, strengthening and stretching exercises. Both groups individually followed programs of 60-min session three times per week for 12 weeks in the outpatient setting. The Disability Arm Shoulder Hand questionnaire (DASH; scores range from 0 to 100; primary outcome), a Pain intensity Numerical Rating Scale (scores range 0 to 10; secondary outcomes), and the Short-Form Health Survey (scores range from 0 to 100; secondary outcomes) assessed the interventions. Participants were evaluated before surgery, before and after rehabilitation (primary endpoint), and at the one-year follow-up (secondary endpoint). A linear mixed model analysis for repeated measures was carried out for each outcome measure (p < 0.05). Results Time, group and time by group showed significant effects for all outcome measures in favour of the experimental group. The DASH and the DASH work achieved clinically important between-group differences of 16.0 points (95% confidence interval [C.I.] 7.3 to 24.7) and 19.7 (95% C.I. 9.0 to 30.5) at follow-up, respectively. The NRS achieved a between-group difference of 2.9 (95% C.I. 1.0 to 3.9) at follow-up. As for SF-36, there were between-group differences ranging from 17.9 to 37.0 at follow-up. Conclusions A rehabilitation program based on task-oriented exercises was useful in improving disability, pain, and quality of life in working patients after PHFs. Improvements lasted for at least 12 months. Trial registration On 16/12/2019, the trial was retrospectively registered in the ISRCTN registry with the ID number 17996552.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ewa Bejer-Oleńska ◽  
Michael Thoene ◽  
Andrzej Włodarczyk ◽  
Joanna Wojtkiewicz

Aim. The aim of the study was to determine the most commonly diagnosed neoplasms in the MRI scanned patient population and indicate correlations based on the descriptive variables. Methods. The SPSS software was used to determine the incidence of neoplasms within the specific diagnoses based on the descriptive variables of the studied population. Over a five year period, 791 patients and 839 MRI scans were identified in neoplasm category (C00-D48 according to the International Statistical Classification of Diseases and Related Health Problems ICD-10). Results. More women (56%) than men (44%) represented C00-D48. Three categories of neoplasms were recorded. Furthermore, benign neoplasms were the most numerous, diagnosed mainly in patients in the fifth decade of life, and included benign neoplasms of the brain and other parts of the central nervous system. Conclusions. Males ≤ 30 years of age with neoplasms had three times higher MRI scans rate than females of the same age group; even though females had much higher scans rate in every other category. The young males are more often selected for these scans if a neoplasm is suspected. Finally, the number of MRI-diagnosed neoplasms showed a linear annual increase.


2009 ◽  
Vol 16 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Valentina Zipoli ◽  
Benedetta Goretti ◽  
Bahia Hakiki ◽  
Gianfranco Siracusa ◽  
Sandro Sorbi ◽  
...  

Significant cognitive impairment has been found in 20—30% of patients with clinically isolated syndromes suggestive of multiple sclerosis. In this study we aimed to assess the prognostic value of the presence of cognitive impairment for the conversion to multiple sclerosis in patients with clinically isolated syndromes. All patients with clinically isolated syndromes consecutively referred to our centre since 2002 and who had been followed-up for at least one year underwent cognitive assessment through the Rao’s Battery and the Stroop test. Possible predictors of conversion to clinically definite multiple sclerosis were evaluated through the Kaplan Meier curves and Cox regression analysis. A total of 56 patients (41 women; age 33.2 ± 8.5 years; expanded disability scale score 1.2 ± 0.7) were recruited. At baseline, 32 patients (57%) fulfilled McDonald’s criteria for dissemination in space. During the follow-up (3.5 ± 2.3 years), 26 patients (46%) converted to a diagnosis of multiple sclerosis. In particular, 64% of patients failing ≥ 2 tests and 88% of patients failing ≥ 3 tests converted to multiple sclerosis. In the Cox regression model, the failure of at least three tests (HR 3.3; 95% CI 1.4—8.1; p = 0.003) and the presence of McDonald’s dissemination in space at baseline (HR 3.8; 95% CI 1.5—9.7; p = 0.005), were found to be predictors for conversion to multiple sclerosis. We conclude that cognitive impairment is detectable in a sizable proportion of patients with clinically isolated syndromes. In these subjects cognitive impairment has a prognostic value in predicting conversion to multiple sclerosis and may therefore play a role in therapeutic decision making.


Author(s):  
Normand L. Proulx ◽  
Mark S. Freedman ◽  
James W. Chan ◽  
Baldwin Toye ◽  
Cathy C. Code

ABSTRACT:Objective:To describe a case of Pasteurella multocida meningitis associated with acute disseminated encephalomyelitis (ADEM).Case report:A 33-year-old woman employed in a dog pound presented herself to hospital with fever and meningismus and was found to have culture positive Pasteurella multocida meningitis. Despite appropriate antibiotic treatment her clinical course was characterized by a persistent fever and worsening encephalopathy, which prompted further neurological investigation. Spinal fluid exam and serial MRI scans as well as her one-year clinical course were found to be compatible with ADEM.Conclusion:Persistent fever and worsening encephalopathy in meningitis may indicate a para-infectious immune process such as ADEM, and may serve as indications for further neurological investigation.


1981 ◽  
Vol 11 (3) ◽  
pp. 535-550 ◽  
Author(s):  
A. H. Mann ◽  
R. Jenkins ◽  
E. Belsey

SYNOPSISOne hundred patients, selected to be representative of those attending general practitioners with non-psychotic psychiatric disorders were followed up for one year. standard assessments of mental state, personality, social stresses and supports were carried out for each patient at the outset and after a year.The outcome for this cohort determined both by the level of psychiatric morbidity at interview after one year and by the pattern of the psychiatric morbidity during the year has been analysed with reference to the assessment measures. Discriminant function analysis indicates that the initial estimate of the severity of the psychiatric morbidity and a rating of the quality of the social life at the time of follow-up are the only factors that significantly predict the psychiatric state after one year. Social measures also predict a pattern of illness charactorized by a rapid recovery after the initial assessemtn. Patients who reported continuous psychiatric morbidity during the year were, older, physically ill and very likely to have recevied psychotropic drugs. Receipt of this medication during the year was associated with initial assessments of abnormality of personality, older age, and a diagnosis of depression.The findings of this study are seen to support a triaxial assessment and classification of non-psychotic psychiatirc disorders, with symptoms, personality and social state being rated independently.


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