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Journal of Psychopharmacology (Oxford,... Nov 2023Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder (MDD) is a leading cause of global disability. Several lines of evidence implicate the dopamine system in its pathophysiology. However, the magnitude and consistency of the findings are unknown. We address this by systematically reviewing in vivo imaging evidence for dopamine measures in MDD and meta-analysing these where there are sufficient studies.
METHODS
Studies investigating the dopaminergic system using positron emission tomography or single photon emission computed tomography in MDD and a control group were included. Demographic, clinical and imaging measures were extracted from each study, and meta-analyses and sensitivity analyses were conducted.
RESULTS
We identified 43 studies including 662 patients and 801 controls. Meta-analysis of 38 studies showed no difference in mean or mean variability of striatal D receptor availability ( = 0.06, = 0.620), or combined dopamine synthesis and release capacity ( = 0.19, = 0.309). Dopamine transporter (DAT) availability was lower in the MDD group in studies using DAT selective tracers ( = -0.56, = 0.006), but not when tracers with an affinity for serotonin transporters were included ( = -0.21, = 0.420). Subgroup analysis showed greater dopamine release ( = 0.49, = 0.030), but no difference in dopamine synthesis capacity ( = -0.21, = 0.434) in the MDD group. Striatal D receptor availability was lower in patients with MDD in two studies.
CONCLUSIONS
The meta-analysis indicates striatal DAT availability is lower, but D receptor availability is not altered in people with MDD compared to healthy controls. There may be greater dopamine release and lower striatal D receptors in MDD, although further studies are warranted. We discuss factors associated with these findings, discrepancies with preclinical literature and implications for future research.
Topics: Humans; Dopamine; Depressive Disorder, Major; Tomography, Emission-Computed, Single-Photon; Positron-Emission Tomography; Receptors, Dopamine D2; Dopamine Plasma Membrane Transport Proteins
PubMed: 37811803
DOI: 10.1177/02698811231200881 -
Knee Surgery, Sports Traumatology,... Aug 2023Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by... (Review)
Review
Cell-based therapies have disease-modifying effects on osteoarthritis in animal models. A systematic review by the ESSKA Orthobiologic Initiative. Part 2: bone marrow-derived cell-based injectable therapies.
PURPOSE
Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models.
METHODS
A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE's tool.
RESULTS
Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%.
CONCLUSION
This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice.
LEVEL OF EVIDENCE
II.
Topics: Animals; Bone Marrow; Osteoarthritis; Synovial Membrane; Disease Models, Animal; Injections, Intra-Articular; Mesenchymal Stem Cell Transplantation; Osteoarthritis, Knee
PubMed: 36823238
DOI: 10.1007/s00167-023-07320-3 -
Alzheimer's Research & Therapy Mar 2024Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid...
BACKGROUND
Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.
METHODS
Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.
RESULTS
We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.
CONCLUSIONS
These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Topics: Male; Humans; Female; Progranulins; Frontotemporal Dementia; Intercellular Signaling Peptides and Proteins; Virulence; Mutation; Membrane Proteins; Nerve Tissue Proteins
PubMed: 38539243
DOI: 10.1186/s13195-024-01420-z -
Annals of Medicine and Surgery (2012) Jul 2023Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are...
UNLABELLED
Despite the significant research and development of COVID-19 diagnostic and therapeutic approaches, the virus still poses a concern, particularly to groups that are already vulnerable. Several individuals experienced cardiac problems like myocardial infarction, arrhythmia, heart failure, cardiomyopathy, myocarditis, and pericarditis after they had recovered from the infection. Early diagnosis and timely management of sequelae are part of the therapy. However, there are gaps in the knowledge of the diagnostic and definitive treatment options for COVID-19 myocarditis. This review focuses on myocarditis associated with COVID-19.
OBJECTIVE
This systemic review provides the most recent overview of myocarditis caused by COVID-19, including clinical manifestations, diagnostic techniques, available treatments, and outcomes.
METHODS
The PubMed, Google Scholar, and ScienceDirect servers were used to conduct a systematic search in compliance with the PRISMA guidelines. Boolean search terms included "(COVID-19)" OR "(COVID19)" OR "(COVID-19 VIRUS INFECTION)" AND "(MYOCARDITIS)". The results were tabulated and analyzed.
RESULTS
A total of 32 studies, including 26 case reports and 6 case series, were included in the final analysis, and 38 cases of COVID-19-associated myocarditis were analyzed. Middle-aged men constituted the most affected population (60.52%). Dyspnoea (63.15%), chest pain or discomfort (44.73%), and fever (42.10%) were the prevalent presentations. ST-segment abnormalities were reported in 48.38% of cases on electrocardiography testing. Leucocytic infiltration (60%) was the frequent finding obtained on endomyocardial biopsy. Cardiac magnetic resonance imaging yielded myocardial oedema (63.63%), and late gadolinium enhancement (54.54%) as the most common findings. Reduced ejection fraction (75%) was the frequent result obtained on echocardiography. Corticosteroids (76.31%) and immunomodulators (42.10%) were the well-established in-hospital medications. Veno-arterial extracorporeal membrane oxygenation (35%) was the most common intervention used to support the treatment. The frequent in-hospital complications were cardiogenic shock (30.76%), followed by pneumonia (23.07%). The mortality rate was 7.9%.
CONCLUSION
Early detection and timely management of myocarditis are essential to reduce the risk of developing further complications. It is crucial to emphasize the need to evaluate COVID-19 as a possible cause of myocarditis in populations that are young and healthy to avoid fatal consequences.
PubMed: 37427189
DOI: 10.1097/MS9.0000000000000964 -
Annals of Medicine and Surgery (2012) May 2024Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains... (Review)
Review
BACKGROUND
Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols.
METHODS
Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949).
RESULTS
Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap.
CONCLUSIONS
Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.
PubMed: 38694314
DOI: 10.1097/MS9.0000000000001952 -
Clinical Cardiology May 2024The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the ECMO system, but this comes with an increased risk of bleeding. Evidence on the use of anti-Xa-guided monitoring to prevent bleeding during ECMO support is limited. Therefore, we aimed to analyze the association between anti-factor Xa-guided anticoagulation and hemorrhage during ECMO.
METHODS
A systematic review and meta-analysis was performed (up to August 2023).
PROSPERO
CRD42023448888.
RESULTS
Twenty-six studies comprising 2293 patients were included in the analysis, with six works being part of the meta-analysis. The mean anti-Xa values did not show a significant difference between patients with and without hemorrhage (standardized mean difference -0.05; 95% confidence interval [CI]: -0.19; 0.28, p = .69). We found a positive correlation between anti-Xa levels and unfractionated heparin dose (UFH; pooled estimate of correlation coefficients 0.44; 95% CI: 0.33; 0.55, p < .001). The most frequent complications were any type of hemorrhage (pooled 36%) and thrombosis (33%). Nearly half of the critically ill patients did not survive to hospital discharge (47%).
CONCLUSIONS
The most appropriate tool for anticoagulation monitoring in ECMO patients is uncertain. Our analysis did not reveal a significant difference in anti-Xa levels in patients with and without hemorrhagic events. However, we found a moderate correlation between anti-Xa and the UFH dose, supporting its utilization in monitoring UFH anticoagulation. Given the limitations of time-guided monitoring methods, the role of anti-Xa is promising and further research is warranted.
Topics: Extracorporeal Membrane Oxygenation; Humans; Hemorrhage; Factor Xa Inhibitors; Anticoagulants; Blood Coagulation; Factor Xa; Risk Factors
PubMed: 38693831
DOI: 10.1002/clc.24273