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Biomolecules Jul 2023The recurrence rate in patients who undergo surgery for abdominal wall hernias (AWHs) is high. AWHs have been hypothesized to be a disease of the extracellular matrix,... (Review)
Review
The recurrence rate in patients who undergo surgery for abdominal wall hernias (AWHs) is high. AWHs have been hypothesized to be a disease of the extracellular matrix, which is supported by evidence showing a high incidence of AWHs in patients with connective tissue disorders. This study aimed to investigate the most recent literature studies describing the levels of several matrix metalloproteinases (MMPs) in the blood and fascia, with the objective of better clarifying the pathogenetic role of matrix metalloproteinases (MMPs) and their inhibitors in inguinal hernias (IHs). A systematic literature search was conducted using the PubMed, Scopus, and Web of Science electronic databases to identify eligible studies. The identified studies were included in the analysis, and a qualitative synthesis of the results is provided to describe the most recent findings. Seventeen studies were included. An association between MMP-2 and direct IHs has also been demonstrated. MMP-1, MMP-2, MMP-9, MMP-12, and MMP-13 levels were increased in both the serum and fascia of patients with IHs. The analysis of inhibitors showed an increase in tissue inhibitors of metalloproteinases (TIMPs), specifically TIMP-1 in IHs, particularly in direct hernias, and a reduction in TIMP-2 in the biopsy samples of the transversalis fascia. In contrast, a reduction in TIMP-1 and an increase in TIMP-2 levels have been reported only in the serum of patients with IHs. Metalloproteinases play a crucial role in the pathogenesis of IHs. The analysis of other molecules, such as TIMPs or their correlation with specific genes, is enhancing our understanding of the pathophysiology of IHs. However, more prospective studies, including comprehensive clinical and laboratory data collection, are required to confirm the relationship between the studied biomarkers and the risk of IHs.
Topics: Humans; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Hernia, Inguinal; Matrix Metalloproteinase 2; Prospective Studies; Tissue Inhibitor of Metalloproteinases
PubMed: 37509159
DOI: 10.3390/biom13071123 -
Revue Neurologique 2024Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein... (Review)
Review
BACKGROUND
Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-β peptide (Aβ), one of the pathological hallmarks of Alzheimer's disease (AD).
OBJECTIVE
To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD.
METHODS
A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239).
RESULTS
Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection.
CONCLUSION
Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.
Topics: Humans; Aged; Alzheimer Disease; Cross-Sectional Studies; ADAM10 Protein; Amyloid beta-Peptides; Biomarkers; Amyloid Precursor Protein Secretases; Membrane Proteins
PubMed: 37460331
DOI: 10.1016/j.neurol.2023.04.002 -
Toxins Apr 2024Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of... (Review)
Review
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Topics: Humans; Mental Disorders; Botulinum Toxins, Type A; Clinical Trials as Topic; Treatment Outcome
PubMed: 38668616
DOI: 10.3390/toxins16040191 -
International Urogynecology Journal Jan 2024To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX)... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION AND HYPOTHESIS
To our knowledge, there are no evidence-based recommendations regarding the optimal prophylactic antibiotic regimen for intradetrusor onabotulinum toxin type A (BTX) injections. This systematic review and meta-analysis was aimed at investigating the optimal prophylactic antibiotic regimen to decrease urinary tract infection (UTI) in patients undergoing BTX for overactive bladder syndrome (OAB).
METHODS
A systematic search of MEDLINE, Embase, CINAHL, and Web of Science was conducted from inception through 30 June 2022. All randomized controlled trials and prospective trials with > 20 subjects undergoing BTX injections for OAB in adults that described prophylactic antibiotic regimens were included. Meta-analysis performed to assess UTI rates in patients with idiopathic OAB using the inverse variance method for pooling.
RESULTS
A total of 27 studies (9 randomized controlled trials, 18 prospective) were included, representing 2,100 patients (69% women) with 19 studies of idiopathic OAB patients only, 6 of neurogenic only, and 2 including both. No studies directly compared antibiotic regimens for the prevention of UTI. Included studies favor the use of antibiotics in patients with idiopathic OAB and favor continuing antibiotics for 2-3 days after the procedure for prevention of UTI. Given the heterogeneity of the data, direct comparisons of antibiotic type or duration could not be performed. Meta-analysis found a 10% UTI rate at 4 weeks and 15% at 12 weeks post-injection.
CONCLUSIONS
Although there are insufficient data to support the use of a specific antibiotic regimen, available studies favor the use of prophylactic antibiotics for 2-3 days in idiopathic OAB patients undergoing BTX injection. Future trials are needed to determine the optimal regimens to prevent UTI in patients undergoing BTX for OAB.
Topics: Adult; Humans; Female; Male; Antibiotic Prophylaxis; Prospective Studies; Botulinum Toxins, Type A; Anti-Bacterial Agents; Urinary Tract Infections; Urinary Bladder, Overactive
PubMed: 37938397
DOI: 10.1007/s00192-023-05665-4 -
Biomolecules Jan 2024Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of... (Review)
Review
Metalloproteinases (MPs) are zinc-dependent enzymes with proteolytic activity and a variety of functions in the pathophysiology of human diseases. The main objectives of this review are to analyze a specific family of MPs, the matrix metalloproteinases (MMPs), in the most common chronic and complex diseases that affect patients' social lives and to better understand the nature of the associations between MMPs and the psychosocial environment. In accordance with the PRISMA extension for a scoping review, an examination was carried out. A collection of 24 studies was analyzed, focusing on the molecular mechanisms of MMP and their connection to the manifestation of social aspects in human disease. The complexity of the relationship between MMP and social problems is presented via an interdisciplinary approach based on complexity paradigm as a new approach for conceptualizing knowledge in health research. Finally, two implications emerge from the study: first, the psychosocial states of individuals have a profound impact on their overall health and disease conditions, which implies the importance of adopting a holistic perspective on human well-being, encompassing both physical and psychosocial aspects. Second, the use of MPs as biomarkers may provide physicians with valuable tools for a better understanding of disease when used in conjunction with "sociomarkers" to develop mathematical predictive models.
Topics: Humans; Biomarkers; Proteolysis; Physicians; Zinc; Matrix Metalloproteinases
PubMed: 38254696
DOI: 10.3390/biom14010096 -
BJOG : An International Journal of... Jul 2024Studies on the changes of extracellular matrix (ECM) in pelvic organ prolapse (POP) are still controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Studies on the changes of extracellular matrix (ECM) in pelvic organ prolapse (POP) are still controversial.
OBJECTIVE
To identify the changes in the ECM in POP patients.
SEARCH STRATEGY
Comprehensive searching in Embase, PubMed, Web of Science and the Cochrane Library was carried out until 23 February 2023.
SELECTION CRITERIA
Studies comparing the protein levels of ECM-related components between women with and without POP.
DATA COLLECTION AND ANALYSIS
Quality and risk of bias were assessed using the Agency for Healthcare Research and Quality assessment. Indicators were pooled with random or fixed effect meta-analysis based on heterogeneity and sub-grouped analysed by the biopsy site.
MAIN RESULTS
Thirty cross-sectional studies were included, comprising 840 POP cases and 755 controls. Overall results showed that the expression of type III collagen (COLIII) and several matrix metalloproteinases (MMP-1, -2 and -9) were increased, whereas those of type I collagen (COLI), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were decreased in patients with POP. Subgroup analysis showed that the expression of COLIII in the anterior vaginal wall (AVW) and COLIII, MMP-2 and -9 in the uterosacral ligament (USL) were consistent with the overall results. However, the expression of COLI and MMP-1 in the AVW showed no difference and the expression of COLI and MMP-1 in the USL is still controversial based on current studies.
CONCLUSIONS
Patients with POP have lower expression of COLI and TIMP-1 and higher expression of COLIII and MMPs compared with non-POP cases, but further studies are required to investigate in specified anatomical sites.
Topics: Humans; Female; Pelvic Organ Prolapse; Extracellular Matrix; Collagen Type III; Vagina; Collagen Type I; Tissue Inhibitor of Metalloproteinase-1; Matrix Metalloproteinases; Cross-Sectional Studies
PubMed: 38291948
DOI: 10.1111/1471-0528.17768 -
The Laryngoscope Jul 2024Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Sialorrhea, also known as drooling, hypersalivation, or ptyalism, has a significant impact on the medical and psychosocial well-being of children. Onabotulinum toxin A (BoNT-A) is the most commonly used botulinum toxin worldwide for the treatment of sialorrhea in children.
OBJECTIVES
To conduct a comprehensive systematic review and meta-analysis to assess the clinical efficacy and potential adverse effects of BoNT-A as a treatment for drooling in children.
METHODS
Cochrane, Embase, and Medline databases were systematically searched (up to May 2023). Out of 535 identified publications, 20 were found eligible for inclusion. A systematic review and meta-analysis were performed to determine the efficacy of BoNT-A treatment in children in reducing the frequency and severity of drooling.
RESULTS
Out of the 20 studies included, a meta-analysis was conducted on the complete dataset of eight studies involving 131 patients. BoNT-A was found to significantly decrease the severity of drooling in patients with sialorrhea (standardized mean difference [SMD], -2.07; 95% confidence interval [CI], -2.91 to -1.23; p < 0.0001) when compared with the conditions before injections using random-effects models. Six studies out of 20 reported dysphagia as an adverse effect after injection. Other side effects included thickness of saliva and pain at the site of injection.
CONCLUSION
BoNT-A is a clinically effective therapy that improves drooling severity in children with sialorrhea. Although there were some adverse side effects reported, they were transient and not severe. Future studies are needed to further evaluate the best techniques and to identify the ideal dosages required to achieve the optimal outcomes. Laryngoscope, 134:3012-3017, 2024.
Topics: Humans; Sialorrhea; Botulinum Toxins, Type A; Child; Neuromuscular Agents; Treatment Outcome; Child, Preschool; Adolescent; Male; Female
PubMed: 38294288
DOI: 10.1002/lary.31277 -
International Journal of Colorectal... Dec 2023Some gut bacteria can produce enzymes (collagenases) that can break down collagen in the intestinal wall. This could be a part of the pathophysiology of anastomotic... (Review)
Review
PURPOSE
Some gut bacteria can produce enzymes (collagenases) that can break down collagen in the intestinal wall. This could be a part of the pathophysiology of anastomotic leakage (AL). This systematic review aimed to investigate if such bacteria were present more frequently in AL patients versus non-AL patients following colorectal surgery.
METHODS
This systematic review was reported according to the PRISMA and AMSTAR guidelines. Before the literature search, a study protocol was registered at PROSPERO (CRD42022363454). We searched PubMed, EMBASE, Google Scholar, and Cochrane CENTRAL on April 9, 2023, for randomized and observational human studies of AL following colorectal surgery with information on gastrointestinal bacteria. The primary outcome was bacteria with the potential to produce collagenase. The risk of bias was assessed with the Newcastle-Ottawa Scale, as all studies were observational.
RESULTS
We included 15 studies, with a total of 52,945 patients, of which 1,747 had AL, and bacteriological information from feces, mucosa, the resected specimen, or drain fluid was presented. In 10 of the 15 studies, one or more collagenase-producing bacteria were identified in the patients with AL. Neither the bacteria nor the collagenase production were quantified in any of the studies. The studies varied greatly in terms of sample material, analytical method, and time of collection. Studies using DNA sequencing methods did not report findings of collagenase-producing bacteria.
CONCLUSION
Collagenase-producing bacteria are more common in patients with AL following colorectal surgery than in patients without AL, but the significance is unclear. From the current studies, it is not possible to determine the pathogenicity of the individual gut bacteria.
Topics: Humans; Anastomotic Leak; Colorectal Surgery; Digestive System Surgical Procedures; Collagenases; Bacteria
PubMed: 38038731
DOI: 10.1007/s00384-023-04562-y -
Immunity, Inflammation and Disease Feb 2024There has been a global increase in the use of electronic cigarettes (EC). However, to our knowledge, no review has summarized or categorized changes in inflammatory... (Meta-Analysis)
Meta-Analysis
CONTEXT
There has been a global increase in the use of electronic cigarettes (EC). However, to our knowledge, no review has summarized or categorized changes in inflammatory biomarkers after EC use in the extant literature.
OBJECTIVE
To evaluate changes in general, cardiopulmonary, and oxidative stress-related inflammatory biomarkers in healthy adults who use ECs.
METHODS
A scoping review was conducted according to the Arksey and O'Malley framework. PubMed and MEDLINE (Ovid) databases were used for our search. After initial pilot searches and discussions, we performed a final search with medical subject headings and plain language terms related to inflammation, biomarkers, ECs, and adult humans. All full-text articles, gray literature, and primary studies dating from the inception of the searched databases to the present were included. Studies of human participants with known confounding medical histories were excluded.
RESULTS
Thirty-seven studies met the inclusion criteria. After short-term (<1 month) use, ECs containing nicotine moderately increased cardiovascular (CV) and oxidative stress markers of inflammation. Of all reported results, 50% of CV biomarkers were increased, and 64% of oxidative stress markers were increased. After long-term (>1 month) use, ECs containing nicotine produced mixed results. Two commonly measured biomarkers in this group, matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6), were elevated in 75% and 60% of measured instances, respectively.
CONCLUSION
The results of studies evaluated in our scoping review suggested that short-term use of nicotine-containing ECs may result in increased CV and oxidative stress inflammation, contributing to potential CV or neurologic disease development. The results of studies evaluated in our scoping review also suggested that long-term use of nicotine-containing ECs resulted in no significant changes in general inflammatory biomarker levels. A rigorous systematic review and meta-analysis is necessary to corroborate our findings and to determine the effect of long-term EC use on MMP-9 and IL-6 levels.
Topics: Adult; Humans; Biomarkers; Electronic Nicotine Delivery Systems; Inflammation; Interleukin-6; Matrix Metalloproteinase 9; Nicotine; Vaping
PubMed: 38353387
DOI: 10.1002/iid3.1170 -
BJU International Jan 2024To evaluate the evidence regarding the therapeutic benefits and safety of oral detrusor relaxing agents (DRAs) in treating neurogenic detrusor overactivity (NDO). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the evidence regarding the therapeutic benefits and safety of oral detrusor relaxing agents (DRAs) in treating neurogenic detrusor overactivity (NDO).
METHODS
A comprehensive search was performed on 1 September 2022. Two authors independently reviewed the articles to extract data using a pre-designed form. The meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A common-effect or random-effects model was used based on the heterogeneity among studies. Bayesian network meta-analysis (NMA) was further performed to make indirect comparisons of antimuscarinics and mirabegron.
RESULTS
A total of 23 randomised controlled trials (RCTs) comprising 1697 patients were included in our analysis. Compared to placebo, the clinical benefits of oral DRAs, along with more adverse events (AEs), were demonstrated in the treatment of NDO. In the subgroup analysis, antimuscarinics significantly improved both urodynamic and bladder diary outcomes (including urinary incontinence episodes, urinary frequency, and residual volume), with a higher rate of AEs, such as xerostomia. Mirabegron improved some of the parameters and had fewer bothersome side-effects in patients with NDO. The NMA showed that none of the antimuscarinics or mirabegron was superior or inferior to the other.
CONCLUSIONS
Detrusor relaxing agents are associated with improved outcomes in patients with NDO and our analysis has added new evidence regarding antimuscarinics. Evidence concerning mirabegron as first-line therapy for NDO is still limited. Well-designed RCTs are still required in this specific population.
Topics: Humans; Urinary Bladder, Neurogenic; Muscarinic Antagonists; Network Meta-Analysis; Botulinum Toxins, Type A; Treatment Outcome; Urinary Bladder, Overactive; Urodynamics; Randomized Controlled Trials as Topic
PubMed: 37500569
DOI: 10.1111/bju.16142