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Journal of Plastic, Reconstructive &... Mar 2020Synkinesis is a negative sequela of facial nerve recovery. Despite the need for effective treatment, controversy exists regarding optimal management and outcome...
Synkinesis is a negative sequela of facial nerve recovery. Despite the need for effective treatment, controversy exists regarding optimal management and outcome reporting measures. The goals of this study were to evaluate the current synkinesis literature and compare the effectiveness of treatment modalities. A search of biomedical databases was performed in May 2019. Full-text English language articles of cohort studies or randomized controlled trials on synkinesis treatment were eligible for inclusion. Reviews, animal studies, and those without assessment of treatment effect were excluded. We found 592 unique citations; 33 articles were included in the final analyses. Nine studies focused on botulinum toxin (BTX-A), 7 on surgery, 5 on physical therapy (PT), and 12 on multimodal therapy. The Sunnybrook Facial Grading System was the most frequently used outcome measure (17 studies, 51.5%). All treatment modalities improved outcomes. Chemodenervation studies showed an average improvement of 17.8% (range 11-33.3%) in the respective outcome measures after treatment. PT improved by 29.7% (range 14.6-41.2%), surgery by 16.6% (range 4.7-41%), and combination therapy by 20.4% (range 5.13-37.5%). Only 21 studies (63.6%) provided data on adverse outcomes. There is lack of high-evidence level data for robust comparisons of postparetic synkinesis treatments; however, this condition is likely effectively treated nonsurgically and requires the support of a specialized multidisciplinary team. Adoption of standardized patient evaluation and outcome reporting methods is necessary for robust comparative effectiveness studies.
Topics: Botulinum Toxins; Combined Modality Therapy; Facial Paralysis; Humans; Nerve Block; Physical Therapy Modalities; Synkinesis
PubMed: 31786138
DOI: 10.1016/j.bjps.2019.10.006 -
Progress in Orthodontics Oct 2021MicroRNAs (miRNAs) are non-coding short, single-stranded RNA molecules that may serve as biomarkers for various inflammatory and molecular mechanisms underlying bone and... (Review)
Review
BACKGROUND
MicroRNAs (miRNAs) are non-coding short, single-stranded RNA molecules that may serve as biomarkers for various inflammatory and molecular mechanisms underlying bone and tissue remodeling consequent to orthodontic force application.
METHODS
A thorough literature search in major databases was conducted in March 2021 to generate evidence for miRNAs in orthodontics, with prior PROSPERO registration. The initial search revealed 920 articles, subjected to strict selection criteria according to PRISMA, and resulted in final inclusion of four studies. Quality assessment by QUADAS-2 classified three studies as unclear risk-of-bias while the applicability was high. Further, bioinformatic analysis was performed to identify the target genes from the miRNA database (miRDB) and TargetScan databases and their protein-protein interaction pathways with the STRING analysis.
RESULTS
Multiple miRNAs in gingival crevicular fluid (GCF) of orthodontic patients were seen, including miRNA-21, 27(a/b), 29(a/b/c), 34,146(a/b), 101, and 214 along with matrix metalloproteinases (MMPs)-1, 2, 3, 8, 9, 14 in one study. A statistically significant increase in expression of miRNA-29a/b/c,101, 21 from pre-treatment (before initiation of retraction) was seen to reach a peak at 4-6 weeks (wk) of retraction. On the contrary, miRNA-34a showed downregulation from the 1 day to 4 wk of retraction and also, negatively correlated with MMPs-2,9,14 levels at the same observation times. The distance of canine movement showed mild correlation with miRNA-27a/b, 214 at 2 wk of retraction. Bioinformatics revealed 1213 mutual target genes which were analyzed for inter-relational pathways using Cytoscape plugin, MCODE. Further, 894 prominent protein interactions were identified from the STRING database and SMAD4, IGF1, ADAMTS6, COL4A1, COL1A1, COL3A1, FGFR1, COL19A1, FBN1, COL5A1, MGAT4A, LTBP1, MSR1, COL11A1, and COL5A3 were recognized as the hub genes. Their interactions were able to isolate multiple miRNAs: hsa-miR-34a-5p, hsa-miR-29b-2-5p, hsa-miR-29b-3p, hsa-miR-34a-3p, hsa-miR-27a-5p, hsa-miR-29a-5p, hsa-miR-29b-1-5p, hsa-miR-29c-3p, hsa-miR-214-5p, hsa-miR-27a-3p, hsa-miR-29a-3p, hsamiR-146-5p, which were found promising as biomarkers for tooth movement.
CONCLUSIONS
Our results support using miRNAs as biomarkers in varied orthodontic study designs and for inter-relationships with pathological settings like periodontal disease, pre-malignancies, or conditions like obesity or metabolic irregularities, etc. The identified target genes and their protein interaction pathways can be used to propose precision therapies, focusing on ideal tooth movement with minimal iatrogenic side-effects.
Topics: ADAMTS Proteins; Biomarkers; Computational Biology; Gingival Crevicular Fluid; Humans; MicroRNAs; Orthodontics; Saliva
PubMed: 34632546
DOI: 10.1186/s40510-021-00377-1 -
BMC Cardiovascular Disorders May 2020We performed a systematic review and meta-analysis of the Matrix metalloproteinases (MMP)-9 (C1562T), MMP-9 (R279Q), MMP-9 (P574R) and MMP-9 (R668Q) polymorphisms and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We performed a systematic review and meta-analysis of the Matrix metalloproteinases (MMP)-9 (C1562T), MMP-9 (R279Q), MMP-9 (P574R) and MMP-9 (R668Q) polymorphisms and risk of Coronary Artery Disease (CAD).
METHODS
After a systematic literature search, pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association.
RESULTS
We identified 40 studies with 11,792 cases and 8280 controls for C1562T, 7 case-control studies with 5525 cases and 2497 controls for R279Q, 2 studies with 1272 cases and 785 controls for P574R, and 2 studies with 1272 cases and 785 controls for R668Q. MMP-9 (C1562T) polymorphism was associated with increased risk of CAD under dominant model (OR = 1.41, P < 0.001), recessive model (OR = 1.59, P < 0.001), allelic model (OR = 1.38, P < 0.001), TT vs. CC model (OR = 1.70, P < 0.001), and CT vs. CC model (OR = 1.35, P < 0.001). Moreover, the subgroup analysis based on the continent of the study populations in this SNP indicated strong significant association in Asians but not in Europeans. Subgroup analysis was not performed in Africa, America and Oceania, due to lack of sufficient data.
CONCLUSIONS
Our meta-analysis revealed that MMP-9 (C1562T) SNP conferred a susceptibility risk for CAD in the overall analysis and Asian population. The overall analysis and subgroup analysis of the other three SNPs reject the association between MMP-9 polymorphisms and the risk of CAD. Although the results should interpret with caution because of small sample size of included studies in these three SNPs.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Coronary Artery Disease; Female; Genetic Predisposition to Disease; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Phenotype; Polymorphism, Genetic; Risk Assessment; Risk Factors
PubMed: 32429880
DOI: 10.1186/s12872-020-01510-4 -
Journal of Medical Economics 2021The objective of this study was to compare clinical- and cost-effectiveness of type A botulinum toxin (BoNT-A) therapies for management of pediatric upper limb...
Comparative efficacy, safety, and cost-effectiveness of abobotulinumtoxinA and onabotulinumtoxinA in children with upper limb spasticity: a systematic literature review, indirect treatment comparison, and economic evaluation.
OBJECTIVE
The objective of this study was to compare clinical- and cost-effectiveness of type A botulinum toxin (BoNT-A) therapies for management of pediatric upper limb spasticity, including AbobotulinumtoxinA (aboBoNT-A) and Onabotulinumtoxin A (onaBoNT-A).
METHODS
Systematic literature review and indirect treatment comparisons were conducted of randomized controlled trials reporting efficacy and safety outcomes. Efficacy was characterized by Modified Ashworth Scale (MAS) and Ashworth Scale (AS) up to 16-weeks post-injection. Results were used to inform a cost-effectiveness model with a 1-year time horizon, linking response rates with health-related quality-of-life (HRQoL) outcomes and costs from a UK perspective. Other data sources included in the cost-effectiveness model were drug unit costs, health care resource utilization based on UK physician survey, and HRQoL impacts of adverse events associated with oral anti-spasticity therapies. Results were characterized as cost per quality-adjusted life year and cost per responder.
RESULTS
Six studies were included in evidence syntheses. There was a trend towards greater response rate for aboBoNT-A which resulted in improved HRQoL and lower annual costs compared with onaBoNT-A. Safety outcomes were similar across BoNT-A therapies. In cost-effectiveness analysis, aboBoNT-A was an economically dominant therapy with respect to cost per quality-adjusted life year. The cost per responder at 1 year was estimated to be £39,056 for aboBoNT-A vs. £54,831 for onaBoNT-A.
LIMITATIONS AND CONCLUSIONS
Based on observed safety and efficacy data, aboBoNT-A is estimated to result in higher treatment response and consequently increased quality-of-life and reduced costs, vs. onaBoNT-A in children with upper limb spasticity. Limitations to the study include study heterogeneity limited details available for onaBoNT-A studies (e.g. use of physical therapy), and limited availability of responder data. Where assumptions were required, they were made to be conservative towards aboBoN-A.
Topics: Botulinum Toxins, Type A; Child; Cost-Benefit Analysis; Humans; Muscle Spasticity; Upper Extremity
PubMed: 34340647
DOI: 10.1080/13696998.2021.1957582 -
Frontiers in Cellular and Infection... 2023The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of... (Review)
Review
INTRODUCTION AND AIM
The presence of host collagenases in the degradation of the protein matrix at later stages of carious dentin lesions development, as well as the potential involvement of bacterial collagenases, have been suggested but lack conclusive evidence. This study aims to conduct a systematic review to comprehensively assess the profile of host and bacterial-derived collagenolytic proteases in both root and coronal dentin carious lesions.
METHODS
The search was performed in eight databases and the grey literature. Studies evaluating dentin, extracted teeth, or biofilms from natural caries lesions were included. The methodological quality of studies was assessed using the Joanna Briggs Institute tool. Synthesis of the results and the certainty of evidence were performed following the Synthesis without Meta-analysis (SWiM) checklist and GRADE approach for narrative synthesis, respectively.
RESULTS
From 935 recovered articles, 18 were included. Although the evidence was very uncertain, it was possible to suggest that 1) MMP-2, MMP-9, MMP-13, and CT-B may be increased in carious dentin when compared to sound dentin; 2) there is no difference in MMP-2 presence, while MMP-13 may be increased in root when compared to coronal carious dentin; 3) there is no difference of MMP-2 and MMP-9 expression/activity before and after cavity sealing; 4) MMP-8 may be increased in the dentin before cavity sealing compared to dentin after cavity sealing; 5) there is no difference of MMP-20 in irradiated vs. non-irradiated carious dentin. MMP-20 probably reduces in carious outer dentin when compared to carious inner dentin (moderate certainty). Genes encoding bacterial collagenolytic proteases and protein-degrading bacteria were detected in coronal and root carious lesions.
CONCLUSION
Trends in the direction of the effect were observed for some collagenolytic proteases in carious dentin, which may represent a potential target for the development of new treatments. (Protocol register-PROSPERO: CRD42020213141).
Topics: Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Dentin; Matrix Metalloproteinase 13; Peptide Hydrolases; Matrix Metalloproteinase 20; Collagenases; Bacteria; Dental Caries
PubMed: 38029242
DOI: 10.3389/fcimb.2023.1278754 -
Scandinavian Journal of Pain Oct 2021The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The pathogeneses of chronic tension-type headache (CTTH) and cervicogenic headache (CEH) are not well established. Peripheral activation or sensitization of myofascial nociceptors is suggested as a potential mechanism and injections of botulinum toxin (BONTA) have thus been used in the treatment for both headache conditions. BONTA inhibits the release of acetylcholine at the neuromuscular junction and inhibits contraction of skeletal muscles. If the pain is precipitated by increased tone in cervical muscles, local injections of BONTA could represent a prophylactic measure. However, the treatment is still controversial, and a thorough assessment of the current evidence is required. This review aims to assess the evidence of BONTA injection as a prophylactic treatment for CTTH and CEH by reviewing and examining the quality of placebo-controlled, randomized trials.
METHODS
Data sources: we searched in the following databases: PubMed (including Medline), Embase, Cochrane Central register of Controlled Trials, Cinahl, Amed, SCOPUS and Google Scholar including other repository sources. Both MeSH and free keywords were used in conducting the systematic search in the databases. The search covered publications from the root of the databases to November 2020.
STUDY ELIGIBILITY CRITERIA
The review included RCTs, comparing single treatment of BONTA with placebo on patients with CTTH or CEH above 18 years of age, by measuring pain severity/relief or headache frequency.
DATA EXTRACTION
The following data were extracted: year of publication, country, setting, trial design, number of participants, injection procedure, BONTA dosages, and clinical outcome measures.
STUDY APPRAISAL
To assess validity and quality, and risk of bias, the Oxford Pain Validity Scale, Modified Jadad Scale, last version of Cochrane Collaboration's tool for assessing risk of bias (RoB 2), and the CONSORT 2010 Checklist were used. The trials were assessed, and quality scored independently by two of the reviewers. A quantitative synthesis and meta-analyses of headache frequency and intensity were performed.
RESULTS
We extracted 16 trials, 12 on prophylactic BONTA treatment for CTTH and four on CEH. Of these 12 trials (8 on CTTH and 4 on CEH) were included in the quantitative synthesis. A majority of the trials found no significant difference on the primary outcome measure when BONTA treatment was compared with placebo. Three "positive" trials, reporting significant difference in favor of BONTA treatment, but two of these were hampered by low validity and quality scores and high risk of bias.
CONCLUSIONS
There is no clear clinical evidence supporting prophylactic treatment with BONTA for CTTH or CEH.
Topics: Botulinum Toxins, Type A; Headache; Headache Disorders; Humans; Post-Traumatic Headache; Randomized Controlled Trials as Topic; Tension-Type Headache
PubMed: 34090319
DOI: 10.1515/sjpain-2021-0038 -
Developmental Medicine and Child... Jan 2023To describe the clinical course of pain intensity in individuals with cerebral palsy (CP) resulting from usual care or specific interventions. (Review)
Review
AIM
To describe the clinical course of pain intensity in individuals with cerebral palsy (CP) resulting from usual care or specific interventions.
METHOD
We conducted an exploratory prognostic systematic review searching electronic databases from inception to 31st December 2021. Evidence from low and moderate risk-of-bias studies was synthesized.
RESULTS
We retrieved 2275 citations; 18 studies met the inclusion criteria and 10 were synthesized. The course of pain intensity in children with CP receiving usual care was stable over 15 weeks (χ = 1.8, p = 0.5). Children who received continuous intrathecal baclofen (CITB) reported significant pain intensity reduction (visual analogue scale [VAS] = -4.2 out of 10, 95% confidence interval [CI] = -6.3 to -2.1]) 6 months postinsertion but similar children receiving usual care had no significant change over 6 months (VAS = 1.3 out of 10, 95% CI = -1.3 to 3.6). Children receiving botulinum neurotoxin A (BoNT-A) injections had significant decreases in pain after 1 month (numeric rating scale = -6.5, 95% CI = -8.0 to -5.0). Adults with chronic pain receiving usual care reported stable pain intensity over time; pain intensity improved in ambulatory adults exercising and those treated surgically for cervical myelopathy.
INTERPRETATION
The course of pain intensity in individuals with CP is unclear. Evidence suggests that children and adults receiving usual care had stable pain intensity over the short or long term. Interventions (CITB and BoNT-A in children and exercise and surgical treatment for cervical myelopathy in adults) had pain intensity reduction. Larger study samples are needed to confirm these results.
WHAT THIS PAPER ADDS
Pain intensity was stable in children with cerebral palsy (CP) receiving usual care. Adults with CP and chronic pain receiving usual care had stable, persistent pain intensity. Children receiving continuous intrathecal baclofen via pump and botulinum neurotoxin A reported significantly lower pain intensities. Adults with chronic pain and dyskinetic CP and cervical myelopathy reported significantly lower pain intensity with exercise or cervical decompression. Limited high-quality evidence exists describing non-procedural pain changes in individuals with CP.
Topics: Adult; Child; Humans; Baclofen; Botulinum Toxins, Type A; Cerebral Palsy; Chronic Pain; Pain Measurement; Prognosis; Spinal Cord Diseases
PubMed: 35871758
DOI: 10.1111/dmcn.15358 -
Toxins May 2024Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in... (Observational Study)
Observational Study
Chronic migraine (CM) significantly affects underage individuals. The study objectives are (1) to analyze the effectiveness and safety of onabotulinumtoxinA (BTX-A) in adolescents with CM; (2) to review the literature on BTX-A use in the pediatric population. This prospective observational study included patients under 18 years old with CM treated with BTX-A (PREEMPT protocol) as compassionate use. Demographic, efficacy (monthly headache days-MHD; monthly migraine days-MMD; acute medication days/month-AMDM) and side effect data were collected. A ≥ 50% reduction in MHD was considered as a response. Effectiveness and safety were analyzed at 6 and 12 months. A systematic review of the use of BTX-A in children/adolescents was conducted in July 2023. In total, 20 patients were included (median age 15 years [14.75-17], 70% (14/20) females). The median basal frequencies were 28.8 [20-28] MHD, 18 [10-28] MMD and 10 [7.5-21.2] AMDM. Compared with baseline, at 6 months ( = 20), 11 patients (55%) were responders, with a median reduction in MHD of -20 days/month ( = 0.001). At 12 months ( = 14), eight patients (57.1%) were responders, with a median reduction in MHD of -17.5 days/month ( = 0.002). No adverse effects were reported. The literature search showed similar results. Our data supports the concept that BTX-A is effective, well tolerated, and safe in adolescents with CM resistant to oral preventatives.
Topics: Humans; Migraine Disorders; Botulinum Toxins, Type A; Adolescent; Female; Male; Prospective Studies; Chronic Disease; Treatment Outcome; Neuromuscular Agents
PubMed: 38787073
DOI: 10.3390/toxins16050221 -
International Journal of Colorectal... Jan 2021Anastomotic leakage (AL) is the most severe complication following colorectal resection and is associated with increased mortality. The main group of enzymes responsible... (Review)
Review
PURPOSE
Anastomotic leakage (AL) is the most severe complication following colorectal resection and is associated with increased mortality. The main group of enzymes responsible for collagen and protein degradation in the extracellular matrix is matrix metalloproteinases. The literature is conflicting regarding anastomotic leakage and the degradation of extracellular collagen by matrix metalloproteinase-9 (MMP-9). In this systematic review, the possible correlation between anastomotic leakage after colorectal surgery and MMP-9 activity is investigated.
METHODS
Embase, MEDLINE, Cochrane, and Web of Science databases were searched up to 3 February 2020. All published articles that reported on the relationship between MMP-9 and anastomotic leakage were selected. Both human and animal studies were found eligible. The correlation between MMP-9 expression and anastomotic leakage after colorectal surgery.
RESULTS
Seven human studies and five animal studies were included for analysis. The human studies were subdivided into those assessing MMP-9 in peritoneal drain fluid, intestinal biopsies, and blood samples. Five out of seven human studies reported elevated levels of MMP-9 in patients with anastomotic leakage on different postoperative moments. The animal studies demonstrated that MMP-9 activity was highest in the direct vicinity of an anastomosis. Moreover, MMP-9 activity was significantly reduced in areas further proximally and distally from the anastomosis and was nearly or completely absent in uninjured tissue.
CONCLUSION
Current literature shows some relation between MMP-9 activity and colorectal AL, but the evidence is inconsistent. Innovative techniques should further investigate the value of MMP-9 as a clinical biomarker for early detection, prevention, or treatment of AL.
Topics: Anastomosis, Surgical; Anastomotic Leak; Animals; Colorectal Surgery; Digestive System Surgical Procedures; Humans; Matrix Metalloproteinase 9
PubMed: 32865714
DOI: 10.1007/s00384-020-03724-6 -
Endocrinology, Diabetes & Metabolism Apr 2021Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the...
INTRODUCTION
Fibrosis is characterized by dysregulation and accumulation of extracellular matrix. Peyronie's disease and Dupuytren disease are fibroproliferative disorders of the tunica albuginea of the penis and fascia of the hand, respectively. Chronic hyperglycaemia due to diabetes mellitus can also lead to tissue injury and fibrosis. A meta-analysis has shown a relationship between Dupuytren disease and diabetes (overall odds ratio, 3.1; 95% confidence interval, 2.7-3.5). This review explores commonalities in the pathogenesis of Peyronie's disease, Dupuytren disease and diabetes.
METHODS
A search of the PubMed database was conducted using the search terms "diabetes" AND "Peyronie's disease"; and "diabetes" AND "Dupuytren."
RESULTS
Genome-wide association and gene expression studies conducted with tissue from people with Peyronie's disease or Dupuytren disease identified signalling pathways associated with wingless-type mammary-tumour virus integration site signalling, extracellular matrix modulation and inflammation. Biochemical studies confirmed the importance of these pathways in the pathogenesis of fibrosis with Peyronie's disease and Dupuytren disease. Dysregulation of matrix metalloproteinase activity associated with extracellular matrix breakdown was implicated in fibroproliferative complications of diabetes and in the aetiology of Peyronie's disease and Dupuytren disease. A notable percentage of people with diabetes have comorbid Peyronie's disease and/or Dupuytren disease.
CONCLUSIONS
Studies have not been performed to identify fibroproliferative pathways that all 3 conditions might have in common, but data suggest that common pathways are involved in the fibroproliferative processes of Peyronie's disease, Dupuytren disease, and diabetes.
Topics: Chronic Disease; Diabetes Complications; Diabetes Mellitus; Dupuytren Contracture; Extracellular Matrix; Fascia; Female; Fibrosis; Genome-Wide Association Study; Hand; Humans; Hyperglycemia; Male; Matrix Metalloproteinases; Penile Induration; Penis; Signal Transduction
PubMed: 33855203
DOI: 10.1002/edm2.195