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British Journal of Haematology Feb 2024Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX),...
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening haematological condition. Initial treatment involves plasma exchange (PLEX), corticosteroids, caplacizumab and rituximab. In relapsed and refractory cases despite initial treatments, further immune-modulating therapy includes the proteasome inhibitor, bortezomib. Evidence for bortezomib in this setting is limited to case reports and case series. We report our experience and perform a systematic review of the literature. We identified 21 publications with 28 unique patients in addition to our cohort of eight patients treated with bortezomib. The median age of patients was 44 years (IQR: 27-53) and 69% female. They were usually in an initial, refractory presentation of iTTP where they had received PLEX, corticosteroids, rituximab and another line of therapy. After bortezomib administration, 72% of patients had a complete response, with 85% maintaining a durable response without relapse at the last follow-up.
Topics: Humans; Female; Adult; Middle Aged; Male; Bortezomib; Rituximab; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Purpura, Thrombocytopenic, Idiopathic; Adrenal Cortex Hormones; Plasma Exchange; ADAMTS13 Protein
PubMed: 37571963
DOI: 10.1111/bjh.19035 -
The Cochrane Database of Systematic... Jun 2024Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe.
OBJECTIVES
To evaluate the efficacy and safety of treatments used for intractable constipation in children.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome.
MAIN RESULTS
This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 μg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes.
AUTHORS' CONCLUSIONS
We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.
Topics: Humans; Constipation; Child; Randomized Controlled Trials as Topic; Child, Preschool; Adolescent; Defecation; Botulinum Toxins, Type A; Quality of Life; Laxatives; Infant; Bias; Lubiprostone
PubMed: 38895907
DOI: 10.1002/14651858.CD014580.pub2 -
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 -
Aesthetic Plastic Surgery Oct 2023Breast surgeries aim to restore the natural appearance of the breasts with acceptable functional and cosmetic outcomes. However, these surgical procedures may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Breast surgeries aim to restore the natural appearance of the breasts with acceptable functional and cosmetic outcomes. However, these surgical procedures may be associated with considerable adverse events. The present systematic review and meta-analysis was designed to reveal the functional and aesthetic outcomes of botulinum toxins (BTX) injection in patients subjected to breast surgeries.
METHODS
A literature review was performed up to 21 September 2022. All clinical studies included patients older than 18 years old and treated with BTX injection for breast surgeries were included.
RESULTS
The present study included 12 articles, encompassing 496 patients. The average dosage of BTX injection ranged from 20 to 100 units. Injecting BTX significantly reduced the mean post-operative opioid analgesics usage (SMD -1.577; 95% -2.087, -1.067; P < 0.001) and the risk of severe animation deformity (RR 12.37; 95% 1.76, 86.66; P = 0.01). There was a statistically significant higher mean expansion volume per visit in the BTX injection group (SMD 1.166; 95% 0.313, 2.018; P = 0.007). There was no statistically significant impact of BTX injection on the risk of surgical site infection (RR 0.59; 95% 0.15, 2.34; P = 0.45) and seroma (RR 0.51; 95% 0.03, 10.15; P = 0.66).
CONCLUSIONS
The present study revealed the potential benefits of BTX injection in breast surgeries. This included reduced post-operative analgesics, as well as the risk of severe animation deformity. This was accomplished with increased expansion volume per visit and a similar risk of BTX injection-related complications.
LEVEL OF EVIDENCE III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Topics: Humans; Adolescent; Follow-Up Studies; Treatment Outcome; Botulinum Toxins, Type A
PubMed: 37464214
DOI: 10.1007/s00266-023-03466-0 -
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