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International Journal of Molecular... Oct 2023Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine... (Review)
Review
Recently, advances in molecular biology and bioinformatics have allowed a more thorough understanding of tumorigenesis in aggressive PitNETs (pituitary neuroendocrine tumors) through the identification of specific essential genes, crucial molecular pathways, regulators, and effects of the tumoral microenvironment. Target therapies have been developed to cure oncology patients refractory to traditional treatments, introducing the concept of precision medicine. Preliminary data on PitNETs are derived from preclinical studies conducted on cell cultures, animal models, and a few case reports or small case series. This study comprehensively reviews the principal pathways involved in aggressive PitNETs, describing the potential target therapies. A search was conducted on Pubmed, Scopus, and Web of Science for English papers published between 1 January 2004, and 15 June 2023. 254 were selected, and the topics related to aggressive PitNETs were recorded and discussed in detail: epigenetic aspects, membrane proteins and receptors, metalloprotease, molecular pathways, PPRK, and the immune microenvironment. A comprehensive comprehension of the molecular mechanisms linked to PitNETs' aggressiveness and invasiveness is crucial. Despite promising preliminary findings, additional research and clinical trials are necessary to confirm the indications and effectiveness of target therapies for PitNETs.
Topics: Animals; Humans; Pituitary Neoplasms; Pituitary Gland; Neuroendocrine Tumors; Aggression; Tumor Microenvironment
PubMed: 37958702
DOI: 10.3390/ijms242115719 -
Medicine Oct 2023Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Matrix metalloproteinases (MMPs) play a crucial role in the pathogenesis of several chronic diseases including rheumatoid arthritis (RA) and periodontitis (PD). RA patients with periodontitis (RA-PD) are associated with elevated inflammatory burden due to increased production of proinflammatory cytokines. Controlling upregulated MMPs activity in these patients may have potential therapeutic effects. Therefore, aim of this study is to address the focused question: "Do RA subjects with concurrent PD have different levels of MMPs in comparison to RA alone, PD alone and HC subjects?"
METHODS
The systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search from 4 electronic databases (EMBASE, Medline, Web of Science, and Cochrane library) and manual search was performed from inception to July 2023. Quality assessment of each article was done using Newcastle-Ottawa Scale. Meta-analyses derived results were summarized as standardized mean difference (SMD) with 95% confidence intervals.
RESULTS
A total of 879 articles were extracted. Following screening and full text assessment, 9 studies were included. MMP-1, MMP-3, MMP-8, MMP-9, and MMP-13 were consistently elevated in RA-PD subjects. MMP-8 levels were found to be higher in RA-PD subjects compared with RA alone, PD alone, and HC in 3 studies reporting GCF levels (SMD = 1.2; Z = 2.07; P = .04) and 2 studies reporting serum levels (SMD = 0.87; Z = 4.53; P < .00001).
CONCLUSION
RA-PD group showed significantly higher MMP levels in their serum and GCF compared with HC, RA, and PD alone individuals. MMP-8 may serve as a reliable biomarker in the diagnosis and management of RA-PD subjects.
Topics: Humans; Matrix Metalloproteinase 8; Periodontitis; Arthritis, Rheumatoid; Cytokines; Biomarkers; Matrix Metalloproteinase 3
PubMed: 37832126
DOI: 10.1097/MD.0000000000035340 -
BMC Pharmacology & Toxicology Oct 2023Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD).
METHODS
We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I tests. We used the GRADE tool to assess the certainty of evidence (COE).
RESULTS
Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low).
CONCLUSIONS
The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function.
TRIAL REGISTRATION
Our review protocol was registered on PROSPERO (42021288334).
Topics: Humans; Botulinum Toxins, Type A; Sialorrhea; Parkinson Disease; Dental Caries; Treatment Outcome
PubMed: 37828600
DOI: 10.1186/s40360-023-00694-7 -
BMJ Open Oct 2023Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise potential biomarkers of the development of tissue fibrosis induced by TB through a systematic method and meta-analysis.
METHODS
A literature search was performed using keywords according to the topic from electronic databases (ScienceDirect and PubMed) and other methods (websites, organisations and citations). Studies that matched predetermined eligibility criteria were included. The quality assessment tool used was the Quality Assessment of Diagnostic Accuracy Score 2, and the data obtained were processed using Review Manager V.5.3.
RESULTS
Of the 305 studies, 7 met the eligibility criteria with a total sample of 365. The results of the meta-analysis showed that the post-TB group of patients with pulmonary parenchymal fibrosis had a higher transforming growth factor (TGF)-β level (6.09) than the control group (1.82), with a 4.27 (95% CI: 0.92 to 7.61) mean difference. Moreover, patients with residual pleural thickening post-TB had a higher mean of TGF-β (0.61) than the control group (0.56), with a 0.05 (95% CI: 0.04 to 0.06) mean difference. Besides TGF-β, our qualitative synthesis also found that matrix metalloproteinase-1 might have a role in forming and developing pulmonary tissue fibrosis, thus, could be used as a predictor marker in the formation of fibrotic lesions in patients with TB. In addition, several other biomarkers were assessed in the included studies, such as tumour necrosis factor-α, interleukin (IL)-4, IL-8, IL-10, plasminogen activator inhibitor-1 and platelet-derived growth factor. However, this study is not intended to examine these biomarkers.
CONCLUSIONS
There were differences in the results of TGF-β levels in patients with fibrotic lesions compared with controls. TGF-β might be a biomarker of fibrotic tissue formation or increased pulmonary tissue fibrosis in post-TB patients. However, further studies are needed on a larger scale.
Topics: Humans; Transforming Growth Factor beta; Tuberculosis; Fibrosis; Pulmonary Fibrosis; Biomarkers; Matrix Metalloproteinases; Transforming Growth Factors
PubMed: 37827747
DOI: 10.1136/bmjopen-2022-070377 -
Toxins Sep 2023The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain... (Review)
Review
BACKGROUND
The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP).
METHODS
A comprehensive literature search was conducted using Medline, Web of Science, and the Cochrane Library databases. Only randomized clinical trials (RCT) published between 2003 and the end of June 2023, investigating the use of BTX to treat NP, were selected. PICO guidelines were used to select and tabulate the articles.
RESULTS
A total of 6 RCTs were selected. Five articles used BTX injections to treat classical trigeminal neuralgia, and one to treat post-herpetic neuralgia. A total of 795 patients received BTX injections. The selected studies utilised different doses and methods of injections and doses. All the selected studies concluded superiority of BTX injections over placebo for reducing pain levels, and 5 out 6 of them highlighted an improvement in the patient's quality of life. Most of the studies reported transient and mild side effects.
CONCLUSION
There is evidence of the efficacy of BTX injections in orofacial pain management. However, improved study protocols are required to provide direction for the clinical use of BTX to treat various orofacial neuropathic pain disorders.
Topics: Humans; Botulinum Toxins; Facial Pain; Trigeminal Neuralgia; Databases, Factual; Neuralgia
PubMed: 37755967
DOI: 10.3390/toxins15090541 -
European Journal of Physical and... Dec 2023Thoracic outlet syndrome (TOS) is related to the compression and/or the traction of the upper-limb neurovascular bundle, responsible for a chronic painful impairment....
INTRODUCTION
Thoracic outlet syndrome (TOS) is related to the compression and/or the traction of the upper-limb neurovascular bundle, responsible for a chronic painful impairment. Neurogenic TOS (NTOS) is the most common manifestation. It remains a challenging diagnosis and its treatment is also difficult. Botulinum toxin (BTX) has been described to help both the diagnosis and the symptoms improvement.
EVIDENCE ACQUISITION
A systematic literature research was performed using PubMed, ScienceDirect, and Embase databases to collect studies reporting the use of BTX in NTOS management. We followed the PRISMA guidelines, and the included studies were evaluated using the GRADE approach.
EVIDENCE SYNTHESIS
We included 10 original articles representing 555 patients. Various outcomes were considered, and results varied from a study to another. Symptoms relief varied from an absence of BTX effectiveness to 84.1% of improvement; relief duration was also reported from none to 88 days. BTX injections were debatable predictors of surgical procedure successes due to low evidence. There was a huge gap between the studies concerning side-effects of the BTX procedures, from none to 100% of the patients.
CONCLUSIONS
There is no evidence for considering BTX injection as a validated tool for the management of NTOS. There might be a slight effect on symptoms, but outcomes are very variable, which prevents further interpretations. The use of BTX should be evaluated in larger prospective cohorts with more standardized outcomes.
Topics: Humans; Botulinum Toxins; Prospective Studies; Treatment Outcome; Thoracic Outlet Syndrome
PubMed: 37737048
DOI: 10.23736/S1973-9087.23.07815-2 -
Chinese Medical Journal Apr 2024Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18 F-prostate specific membrane antigen positron emission... (Meta-Analysis)
Meta-Analysis
18 F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer: A systematic review and meta-analysis.
BACKGROUND
Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment. 18 F-prostate specific membrane antigen positron emission tomography/computerized tomography ( 18 F-PSMA PET/CT) has several advantages over 68 Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of 18 F-PSMA PET/CT for lymph node staging in medium/high-risk PCa.
METHODS
We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer, 18 F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of 18 F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses.
RESULTS
A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89).
CONCLUSIONS
18 F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The diagnostic efficacy was almost equivalent to that reported for 68 Ga-PSMA PET/CT.
REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO), No. CRD42023391101.
Topics: Humans; Male; Prostatic Neoplasms; Positron Emission Tomography Computed Tomography; Lymph Nodes; Neoplasm Staging; Lymphatic Metastasis; Glutamate Carboxypeptidase II
PubMed: 37690993
DOI: 10.1097/CM9.0000000000002850 -
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 -
Farmacia Hospitalaria : Organo Oficial... 2023Post-stroke spasticity is a common complication in stroke survivors, causing severe burden to patients living with it. The aim of this review was to conduct a...
OBJECTIVE
Post-stroke spasticity is a common complication in stroke survivors, causing severe burden to patients living with it. The aim of this review was to conduct a cost-effectiveness analysis (CEA) of the treatment of post-stroke spasticity, in adults, with abobotulinumtoxinA compared to the best supportive care, based on results from a systematic literature review. Given that abobotulinumtoxinA (aboBoNT-A) is always accompanied by the best supportive care treatment, the CEA compared aboBoNT-A plus the best supportive care with the best supportive care alone.
METHODS
A systematic literature review in EMBASE (including Medline and PubMed), Scopus, and other sources (Google Scholar) was conducted. Articles of all types, providing information on the costs and/or effectiveness measures for the current treatments of post-stroke spasticity in adults were included. The synthesis of information from the review provided the parameters for the design of a CEA of the mentioned treatment of interest. The societal perspective was compared to a perspective where only direct costs were observed.
RESULTS
In total, 532 abstracts were screened. Full information was revised from 40 papers and 13 of these were selected as core papers for full data extraction. Data from the core publications formed the basis for the development of a cost-effectiveness model. In all the included papers physiotherapy was the best supportive care treatment. The cost-effectiveness analysis showed that even in the most conservative scenario, assuming the worst case scenario, the probability of a cost per quality-adjusted life-year (QALY) gained below €40,000, for aboBoNT-A together with physiotherapy is above 0.8, and with certainty below €50,000/QALY when either a direct costs, or a societal perspective was taken. On average, the probabilistic model obtains a negative mean incremental cost-effectiveness ratio of around -15,000 €/QALY.
CONCLUSION
The cost-effectiveness analyses show that aboBoNT-A together with physiotherapy would be a cost-effective treatment compared with physiotherapy alone, independently of the perspective considered.
Topics: Adult; Humans; Cost-Effectiveness Analysis; Cost-Benefit Analysis; Botulinum Toxins, Type A; Physical Therapy Modalities; Quality-Adjusted Life Years
PubMed: 37507277
DOI: 10.1016/j.farma.2023.06.008 -
Medicine Jul 2023The purpose of this meta-analysis was to assess the effectiveness of botulinum toxin type A (BoNT-A) in reducing pain associated with fasciitis. By synthesizing the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The purpose of this meta-analysis was to assess the effectiveness of botulinum toxin type A (BoNT-A) in reducing pain associated with fasciitis. By synthesizing the findings from multiple studies, we aimed to provide a comprehensive evaluation of the current evidence regarding the efficacy of BoNT-A in the treatment of fasciitis pain.
METHODS
To identify studies for our report, we conducted electronic database searches of Embase, PubMed, Web of Science, and the Cochrane Library from their inception to November 20, 2022. We included only randomized controlled trials that examined the therapeutic effects of BoNT-A on fasciitis pain, with the primary outcome measure being the visual analog scale. We conducted statistical analyses using RevMan 5.4 software.
RESULTS
Our final meta-analysis comprised 14 randomized controlled trials involving 537 participants, with 271 patients in the BoNT-A group and 266 patients in the control group. The overall effectiveness of BoNT-A in reducing fasciitis pain was significant, with a mean difference (MD) in visual analog scale score of -2.59 (95% confidence interval [CI], -3.36, -1.82); P < .00001; I2 = 88%. Subgroup analysis revealed that BoNT-A was particularly effective in treating plantar fasciitis (MD = -3.34 [95% CI, -4.08, -2.78]; P < .00001; I2 = 75%), lumbar back fasciitis (MD = -2.17 [95% CI, -3.82, -0.52]; P = .001; I2 = 93%), and neck and shoulder fasciitis (MD = -1.49 [95% CI, -2.76, -0.22]; P = .02; I2 = 61%).
CONCLUSION
BoNT-A has a significant analgesic effect on fasciitis pain. Therefore, BoNT-A presents a promising alternative treatment option for fasciitis (PROSPERO 2022: CRD42022382805).
Topics: Humans; Botulinum Toxins, Type A; Pain; Treatment Outcome; Fasciitis, Plantar; Upper Extremity
PubMed: 37505140
DOI: 10.1097/MD.0000000000034461