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Neurological Sciences : Official... Jun 2023To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome. (Review)
Review
OBJECTIVE
To provide new and comprehensive evidence for diagnosis and management of FOSMN syndrome.
METHODS
We reviewed our database to identify patients with FOSMN syndrome. Online database including PubMed, EMBASE, and OVID were also searched for relevant cases.
RESULTS
We identified a total of 71 cases, including 4 cases from our database and 67 ones from online searching. A predominance of male was observed [44 (62.0%)] with median onset age of 53 (range: 7-75) years old. The median (range) disease duration was 60 (3-552) months at the time of the visit. The initial symptoms could be sensory deficits in face (80.3%) or oral cavity (4.2%), bulbar paralysis (7.0%), dysosmia (1.4%), dysgeusia (4.2%), weakness or numbness of upper limbs (5.6%), or lower limbs (1.4%). Abnormal blink reflex was presented in 64 (90.1%) patients. CSF tests showed elevated protein level in 5 (7.0%) patients. Six (8.5%) patients had MND-related gene mutation. Five (7.0%) patients showed transient responsiveness to immunosuppressive therapy, then deteriorated relentlessly. Fourteen (19.7%) patients died, with an average survival time of around 4 years. Among them, five patients died of respiratory insufficiency.
CONCLUSION
The age of onset, progress of disease course, and prognosis of FOSMN syndrome could be varied significantly. The prerequisites of diagnosis were progressive and asymmetric lower motor neuron dysfunction, with sensory dysfunction which usually showed in face at the onset. Immunosuppressive therapy could be tried in some patients with suspected inflammatory clues. In general, FOSMN syndrome tended to be motor neuron disease with sensory involvement.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Male; Middle Aged; Young Adult; Blinking; Bulbar Palsy, Progressive; Motor Neuron Disease; Mutation; Neurodegenerative Diseases
PubMed: 36864244
DOI: 10.1007/s10072-023-06703-1 -
Arthritis Research & Therapy Nov 2016Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth... (Review)
Review
BACKGROUND
Tendon disease is characterized by the development of fibrosis. Transforming growth factor beta (TGF-β), bone morphogenic proteins (BMPs) and connective tissue growth factor (CTGF) are key mediators in the pathogenesis of fibrotic disorders. The aim of this systematic review was to investigate the evidence for the expression of TGF-β, BMPs and CTGF along tendon disease progression and the response of tendon cells to these growth factors accordingly.
METHOD
We conducted a systematic screen of the scientific literature using the Medline database. The search terms used were "tendon AND TGF-β," "tendon AND BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and overuse models were included.
RESULTS
Thirty-three studies were included. In eight studies the expression of TGF-β, BMPs or CTGF was dysregulated in chronic tendinopathy and tendon tear patient tissues in comparison with healthy control tissues. The expression of TGF-β, BMPs and CTGF was increased and showed temporal changes in expression in tendon tissues from animal injury or overuse models compared with the healthy control (23 studies), but the pattern of upregulation was inconsistent between growth factors and also the type of animal model. No study investigated the differences in the effect of TGF-β, BMPs or CTGF treatment between patient-derived cells from healthy and diseased tendon tissues. Tendon cells derived from animal models of tendon injury showed increased expression of extracellular matrix protein genes and increased cell signaling response to TGF-β and BMP treatments compared with the control cells (two studies).
CONCLUSION
The expression of TGF-β, BMPs and CTGF in tendon tissues is altered temporally during healing in animal models of tendon injury or overuse, but the transition during the development of human tendon disease is currently unknown. Findings from this systematic review suggest a potential and compelling role for TGF-β, BMPs and CTGF in tendon disease; however, there is a paucity of studies analyzing their expression and stimulated cellular response in well-phenotyped human samples. Future work should investigate the dynamic expression of these fibrotic growth factors and their interaction with tendon cells using patient samples at different stages of human tendon disease.
Topics: Animals; Bone Morphogenetic Proteins; Connective Tissue Growth Factor; Fibrosis; Humans; Tendinopathy; Transforming Growth Factor beta
PubMed: 27863509
DOI: 10.1186/s13075-016-1165-0 -
Inflammatory Bowel Diseases Oct 2015Clinical disease severity indices are increasingly being used in choosing treatment and monitoring the response of patients with inflammatory bowel disease (IBD). The... (Review)
Review
BACKGROUND
Clinical disease severity indices are increasingly being used in choosing treatment and monitoring the response of patients with inflammatory bowel disease (IBD). The aim of this study was to systematically review the clinical disease severity indices in IBD and to appraise their measurement properties and methodological quality.
METHODS
We searched the MEDLINE, Embase, and PsycINFO databases for original articles describing the development and/or evaluation of one or more of the measurement properties of clinical disease severity indices used in IBD. We assessed these properties (e.g., internal consistency, reliability, validity, responsiveness) using a standardized checklist.
RESULTS
We examined the full text of 142 articles that we deemed potentially eligible and identified 22 clinical disease severity indices in IBD. No clinical disease index has met all the required measurement properties. All of the validation studies were not descriptive enough to allow assessment of their methodology.
CONCLUSIONS
Although commonly used in multiple clinical trials, none of the clinical disease severity indices in IBD had all the required measurement properties. Further validation studies are required.
Topics: Humans; Inflammatory Bowel Diseases; Reproducibility of Results; Severity of Illness Index; Symptom Assessment
PubMed: 25966838
DOI: 10.1097/MIB.0000000000000438 -
Seminars in Arthritis and Rheumatism Apr 2020ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring...
OBJECTIVE
ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring disease activity, and predicting prognosis and response to therapy. Here, we review the recent development and identification of biomarkers for IgG4-RD.
METHODS
Through extensive literature review and analysis, we updated the biomarkers for IgG4-RD and further put forward our own viewpoints.
RESULTS
In addition to traditional biomarkers, such as serum IgG4 concentration and typical histological characteristics, several novel indicators, including IgG2, serum soluble IL-2 receptor (sIL2R), and cc-chemokine ligand 18 (CCL18), indicate inflammation and fibrosis and can be used to accurately diagnose and predict treatment response. Studies to identify target autoantigens in IgG4-RD have shed light on the unmet need for biomarkers that can identify this disorder. Additionally, both serological and histopathologic immune cells involved in antigen-induced responses, innate immune cells (macrophages, mast cells, and the I-IFN/ IL-33 pathway), as well as subsequent acquired immune cells (T and B cell subsets), may also serve as new biomarkers for IgG4-RD. Since IgG4-RD often clinically manifests with multiple organs involvement, non-invasive PET-CT can improve diagnosis and antidiastole levels.
CONCLUSION
These novel biomarkers provide information to help diagnose IgG4-RD, monitor disease activity, as well as predict prognosis and response to therapy.
Topics: Biomarkers; Chemokines, CC; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Receptors, Interleukin-2
PubMed: 31280934
DOI: 10.1016/j.semarthrit.2019.06.018 -
Neurology Jun 2017To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the placebo and nocebo responses in restless legs syndrome (RLS) and explore their determinants.
METHODS
Databases were searched up to October 2015. Randomized, double-blind, placebo-controlled trials of patients with RLS were included if quantitative data were extractable in the placebo arm. Placebo response was defined as the within-group change from baseline, using any scale measuring RLS severity or disability. Nocebo response was defined as the proportion of patients experiencing adverse events in the placebo arm. Random-effects meta-analysis was used to pool data. Statistical heterogeneity was assessed with statistic. Several predetermined subgroup and sensitivity analysis were performed. PROSPERO registration number is CRD42015027992.
RESULTS
We included 85 randomized controlled trials (5,046 participants). Pooled placebo response effect size was -1.41 (95% confidence interval [CI] -1.56 to -1.25, 64 trials, = 88.1%), corresponding to -6.58 points in the International RLS Study Group Scale (IRLS). Pooled nocebo response was 45.36% (95% CI 40.47%-50.29%, 72 trials; = 89.8%). The placebo and nocebo responses were greater in trials with longer duration, evaluating pharmacologic interventions and idiopathic RLS, and in industry-funded and unpublished studies. The placebo response was considerably smaller in objective as compared to subjective outcomes. In addition, the nocebo response increases proportionally with the placebo response, and has the same predictors.
CONCLUSIONS
The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference, and the frequency of adverse events is also considerable. These results are relevant to inform the design and interpretation of future clinical trials.
Topics: Humans; Placebo Effect; Randomized Controlled Trials as Topic; Restless Legs Syndrome
PubMed: 28490647
DOI: 10.1212/WNL.0000000000004004 -
Nutrients Jan 2016Anthocyanins are dietary flavonoids commonly consumed in the diet, which have been suggested to have a preventative effect on cardiovascular disease (CVD) development... (Review)
Review
Anthocyanins are dietary flavonoids commonly consumed in the diet, which have been suggested to have a preventative effect on cardiovascular disease (CVD) development among epidemiological studies. We systematically reviewed randomized controlled trials (RCTs) testing the effects of purified anthocyanins and anthocyanin-rich extracts on markers of CVD (triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and blood pressure) in both healthy and diseased populations. Eligible studies included RCTs of adults published in English. We searched PubMed, Web of Science Core Collection, and BIOSIS Previews for relevant articles from inception until 1 July 2014. Twelve RCTs representing 10 studies were included in this review. Supplementation with anthocyanins significantly improved LDL cholesterol among diseased individuals or those with elevated biomarkers. Supplementation did not significantly affect other markers of CVD in either healthy individuals or those with elevated markers. No adverse effects of anthocyanins were reported across studies at levels up to 640 mg/day. Limitations of trials in the qualitative analyses include short trial duration and large variability in the dose administered within the trials. Longer-duration trials assessing dose response are needed to adequately determine whether an effect of supplementation exists.
Topics: Adult; Anthocyanins; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cholesterol; Dietary Supplements; Female; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors; Triglycerides
PubMed: 26761031
DOI: 10.3390/nu8010032 -
The Cochrane Database of Systematic... Sep 2017It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is important to minimize placebo rates in randomised controlled trials (RCTs) to efficiently detect treatment differences between interventions. Historically, high placebo rates have been observed in clinical trials of ulcerative colitis (UC). A better understanding of factors influencing placebo rates may lead to more informed clinical trial design.
OBJECTIVES
A systematic review and meta-analysis was conducted to evaluate placebo response and remission rates in RCTs evaluating UC treatments in adult patients.
SEARCH METHODS
Electronic databases (i.e. MEDLINE, EMBASE, and CENTRAL) were searched from inception to 1 March 2017 with no language restrictions applied. Reference lists and conference proceedings of major gastroenterology meetings were also handsearched to identify additional studies.
SELECTION CRITERIA
Placebo-controlled RCTs of adult patients with UC treated with corticosteroids, aminosalicylates, immunosuppressives or biologics were eligible, provided enrolment and outcome assessment was conducted using the Ulcerative Colitis Disease Activity Index (UCDAI) or the Mayo Clinic Score. The minimum trial duration was two weeks for induction trials and four months maintenance trials.
DATA COLLECTION AND ANALYSIS
Pairs of authors independently determined study eligibility and extracted data with any disagreements resolved through consensus. Outcomes of interest included the proportion of patients with clinical response and remission. Trial characteristics such as the design, participant demographics and disease history, interventions, and enrolment and assessment criteria were also recorded. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tool. Pooled placebo response and remission rates and 95% confidence intervals (95% CI) were calculated using a binomial normal model for proportions. Induction of remission and maintenance studies were pooled separately. The impact of study-level characteristics on placebo response and remission rates was investigated using mixed-effects meta-regression analyses with logits of event rates as the outcome variables. An assessment of pooled placebo rates over time was conducted using a cumulative meta-analysis based on date of publication. Publication bias was examined using funnel plots.
MAIN RESULTS
The screening process identified 61 included studies which encompass 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). For induction trials, the pooled estimate of placebo response was 33% (95% CI 30% to 36%) while the pooled estimate of placebo remission was 12% (95% CI 9% to 15%). For maintenance trials, the pooled estimate of placebo response was 23% (95% CI 19% to 28%) while the pooled estimate of placebo remission was 17% (95% CI 10% to 27%).Studies enrolling patients with more active disease confirmed objectively by endoscopy were associated with significantly lower placebo remission and response rates than trials enrolling patients with less active disease (27% versus 4%, OR 2.60, 95% CI 1.25 to 5.42, P = 0.01 for UCDAI endoscopy sub score ≥1 versus ≥ 2 for remission; and 27% versus 4%, OR 1.70, 95% CI 1.02 to 2.82, P = 0.02 for UCDAI endoscopy sub score greater than or equal to one versus greater than or equal to two for response). With respect to drug class, the lowest placebo response and remission rates were observed in trials evaluating corticosteroids (23%; 95% CI 19 to 29%, and 5%; 95% CI 2 to 11%, respectively). Trials of biologics had the highest placebo response rate (35%; 95% CI 30 to 41%), while trials evaluating aminosalicylates had the highest placebo remission rate (18%; 95% CI 12 to 24%). Disease duration of greater than five years prior to enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years (29% versus 47%, respectively; OR 0.54, 95% CI 0.32 to 0.92, P = 0.02). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility (37% versus 32%, respectively; OR 1.70, 95% CI 1.02 to 2.82, P = 0.02). Finally, the time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with a 6% increase in the placebo remission rate (OR 1.06, 95% CI 1.02 to 1.10, P = 0.01).Cumulative meta-analysis indicated a consistent increase in the placebo response rate from 1987 to 2007 (from 13% to 33%), although rates have remained constant from 2008 to 2015 (32% to 34%). Similarly, placebo remission rates increased from 1987 to 2007 (5% to 14%) but have remained constant from 2008 to 2015 (12 to 14%). On meta-regression, there were no statistically significant differences between the 1987-2007 and 2008-2015 point estimates for both response (P = 0.81) and remission (P = 0.32).
AUTHORS' CONCLUSIONS
Placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, class of agent, disease duration, and the time point at which the primary outcome was measured. These observations have important implications for the design and conduct of future clinical trials in UC and will help researchers design trials, determine required sample sizes and also provide useful information about trial design features which should be considered when planning new trials.
Topics: Adult; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Colitis, Ulcerative; Gastrointestinal Hemorrhage; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Placebo Effect; Randomized Controlled Trials as Topic; Rectum
PubMed: 28886205
DOI: 10.1002/14651858.CD011572.pub2 -
Current Alzheimer Research 2021Responsiveness to treatment with cholinesterase inhibitors (ChEIs) is difficult to predict in Alzheimer's disease (AD). In the current review, vascular burden is...
INTRODUCTION
Responsiveness to treatment with cholinesterase inhibitors (ChEIs) is difficult to predict in Alzheimer's disease (AD). In the current review, vascular burden is considered as a potential moderator of treatment responsiveness. Cerebrovascular burden co-occurs in at least 30% of AD brains, although it is debated if vascular pathology plays a causal or synergistic role in AD pathogenesis. Vascular burden, therefore, could potentially limit response to treatment due to limited brain reserve or foster treatment efficacy as those with vascular pathology may represent a subgroup with comparable clinical expression but less progressed AD neurodegeneration.
METHODS
A systematic search of Web of Science, Pubmed, Scopus and EthoS identified 32 papers which met the criteria for inclusion. Association of treatment response and vascular burden across five broad markers are discussed: cerebral hypoperfusion, intima-media thickness, white matter changes, cerebral microbleeds and co-existing diagnosis of cerebrovascular disease.
RESULTS
Analysis of frontal regional cerebral blood flow and intima-media thickness may have predictive ability to distinguish those with AD who may respond optimally to short-term treatment with ChEIs. The impact of white matter changes is less consistent; the majority of studies demonstrates no association with treatment response and those that do implicate changes in executive functioning. There is preliminary evidence that deep cerebral microbleeds limit treatment response in subcortical cognitive domains, but this finding requires replication. The use of diagnosis of co-occurring cerebrovascular disease yields no robust variability in response to ChEIs in AD.
CONCLUSION
There is limited evidence that markers of cerebral hypoperfusion, intima-media thickness and cerebral microbleeds moderate response to ChEIs. Findings for other markers of vascular burden are less consistent and do not support any moderating effect.
Topics: Alzheimer Disease; Brain; Carotid Intima-Media Thickness; Cerebrovascular Circulation; Cerebrovascular Disorders; Cholinesterase Inhibitors; Humans
PubMed: 33855943
DOI: 10.2174/1567205018666210414121227 -
International Journal of Colorectal... May 2023Given the substantial risk of treatment failure in inflammatory bowel disease (IBD), adjuvant therapies may play a role in disease management. We aim to carry out a... (Review)
Review
PURPOSE
Given the substantial risk of treatment failure in inflammatory bowel disease (IBD), adjuvant therapies may play a role in disease management. We aim to carry out a systematic review to examine the effects of structured exercise on the inflammatory response in patients with IBD. Our secondary aim is to examine the effect of structured exercise programmes on body composition given both an increase in visceral obesity and the presence of sarcopenia have deleterious effects on outcomes in IBD.
METHODS
A systematic review was carried out following the Methodological Expectations of Cochrane Intervention Reviews (MECIR) manual and the Cochrane Handbook for Systematic Reviews of Interventions. Title/Abstract and MeSH Terms were used to search for relevant studies.
RESULTS
In total, 1516 records were screened for eligibility, and 148 records were reviewed for eligibility, of which 16 were included and a further 7 studies were identified from hand searching references. Four studies included body composition outcomes, and 14 studies reviewed the inflammatory response to exercise.
CONCLUSION
Further studies of adequate duration are required to include patients with more active disease to demonstrate an inflammatory response to exercise. Body composition measurements including muscle mass and visceral adiposity may play a key role in response to medical therapy in IBD and should be included as exploratory outcomes in future studies. A meta-analysis was not carried out due to the significant heterogeneity amongst studies.
Topics: Humans; Body Composition; Exercise; Inflammation; Inflammatory Bowel Diseases
PubMed: 37227593
DOI: 10.1007/s00384-023-04437-2 -
Frontiers in Immunology 2022Patients with COVID-19 and tuberculosis coinfection are at an increased risk of severe disease and death. We therefore sought to evaluate the current evidence which...
BACKGROUND AND AIM
Patients with COVID-19 and tuberculosis coinfection are at an increased risk of severe disease and death. We therefore sought to evaluate the current evidence which assessed the immune response in COVID-19 and tuberculosis coinfection.
METHODS
We searched Pubmed/MEDLINE, EMBASE, Scopus, and Web of Science to identify articles published between 2020 and 2021. We included observational studies evaluating the immune response in patients with tuberculosis and COVID-19 compared to patients with COVID-19 alone.
RESULTS
Four cross-sectional studies (372 participants) were identified. In patients with asymptomatic COVID-19 and latent tuberculosis (LTBI), increased cytokines, chemokines, growth factors and humoral responses were found. In addition, patients with symptomatic COVID-19 and LTBI had higher leukocytes counts and less inflammation. Regarding patients with COVID-19 and active tuberculosis (aTB), they exhibited decreased total lymphocyte counts, CD4 T cells specific against SARS-CoV-2 and responsiveness to SARS-CoV-2 antigens compared to patients with only COVID-19.
CONCLUSION
Although the evidence is limited, an apparent positive immunomodulation is observed in patients with COVID-19 and LTBI. On the other hand, patients with COVID-19 and aTB present a dysregulated immune response. Longitudinal studies are needed to confirm these findings and expand knowledge.
Topics: COVID-19; Coinfection; Cross-Sectional Studies; Humans; Immunity; Latent Tuberculosis; SARS-CoV-2; Tuberculosis
PubMed: 36090983
DOI: 10.3389/fimmu.2022.992743