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Pharmacological Research May 2024There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed... (Meta-Analysis)
Meta-Analysis
There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.
Topics: Diabetes Mellitus, Type 1; Humans; Immunotherapy; Hypoglycemic Agents; Blood Glucose; Insulin; Glycated Hemoglobin
PubMed: 38531504
DOI: 10.1016/j.phrs.2024.107157 -
World Journal of Emergency Surgery :... Mar 2024Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities.
MATERIALS AND METHODS
We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology.
RESULTS
Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I = 0%). The certainty of the evidence was very low across all outcomes.
CONCLUSION
The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly.
Topics: Humans; Vascular System Injuries; Hemorrhage; Tourniquets; Hospitals; Extremities; Compartment Syndromes
PubMed: 38504263
DOI: 10.1186/s13017-024-00536-9 -
Medicine and Science in Sports and... May 2024Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Platelet-rich plasma (PRP) has been used for arthroscopic rotator cuff repairs (aRCR), but no studies have addressed the impact of platelet concentration. The primary aim was to evaluate whether the PRP cell concentration has an effect on tendon healing after aRCR compared with surgery alone. The secondary aim was to assess the functional and pain outcomes.
MATERIALS AND METHODS
A systematic review was performed with searches in the MEDLINE (PubMed), Scopus, Web of Science, and Cochrane (Central) databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Metanalytic procedures were performed for randomized controlled trials (RCTs), and a subgroup analysis was used for studies with target (approximately 10 6 cells·μL -1 ) or below-target PRP cellular concentrations (app. 5 × 10 5 cells·μL -1 ) regarding the primary outcome of tendon healing.
RESULTS
This review included 10 studies (8 RCTs) with 342 patients in the aRCR + PRP group and 344 patients with isolated aRCR. The risk of bias was low to intermediate (6/4, respectively). Meta-analysis of the RCT revealed that the aRCR + high-concentration PRP group had an approximately 3.9-fold higher chance of healing than the non-PRP group (odds ratio, 3.89; 95% confidence interval, 1.78-8.44; P = 0.0007). No significant difference in healing was found between the aRCR + low-concentration PRP and non-PRP groups (odds ratio, 2.21; 95% confidence interval, 0.66-7.45; P = 0.2). The Constant-Murley score and University of California Los Angeles scores were significantly improved in the aRCR + PRP groups with more than 12 months of follow-up, and no significant differences were found consistently for the American Shoulder and Elbow Society and visual analog scale scores.
CONCLUSIONS
This study highlights that a PRP cell concentration close to the target (10 6 cells·μL -1 ) of patients with aRCR may improve their healing and functional outcomes and that dosing may be potentially useful in therapy.
Topics: Humans; Rotator Cuff Injuries; Rotator Cuff; Treatment Outcome; Wound Healing; Platelet-Rich Plasma; Arthroscopy
PubMed: 38480490
DOI: 10.1249/MSS.0000000000003361 -
International Journal of Molecular... Mar 2024Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful... (Review)
Review
Wound healing is an intricate process involving coordinated interactions among inflammatory cells, skin fibroblasts, keratinocytes, and endothelial cells. Successful tissue repair hinges on controlled inflammation, angiogenesis, and remodeling facilitated by the exchange of cytokines and growth factors. Comorbid conditions can disrupt this process, leading to significant morbidity and mortality. Stem cell therapy has emerged as a promising strategy for enhancing wound healing, utilizing cells from diverse sources such as endothelial progenitor cells, bone marrow, adipose tissue, dermal, and inducible pluripotent stem cells. In this systematic review, we comprehensively investigated stem cell therapies in chronic wounds, summarizing the clinical, translational, and primary literature. A systematic search across PubMed, Embase, Web of Science, Google Scholar, and Cochrane Library yielded 22,454 articles, reduced to 44 studies after rigorous screening. Notably, adipose tissue-derived mesenchymal stem cells (AD-MSCs) emerged as an optimal choice due to their abundant supply, easy isolation, ex vivo proliferative capacities, and pro-angiogenic factor secretion. AD-MSCs have shown efficacy in various conditions, including peripheral arterial disease, diabetic wounds, hypertensive ulcers, bullous diabeticorum, venous ulcers, and post-Mohs micrographic surgery wounds. Delivery methods varied, encompassing topical application, scaffold incorporation, combination with plasma-rich proteins, and atelocollagen administration. Integration with local wound care practices resulted in reduced pain, shorter healing times, and improved cosmesis. Stem cell transplantation represents a potential therapeutic avenue, as transplanted stem cells not only differentiate into diverse skin cell types but also release essential cytokines and growth factors, fostering increased angiogenesis. This approach holds promise for intractable wounds, particularly chronic lower-leg wounds, and as a post-Mohs micrographic surgery intervention for healing defects through secondary intention. The potential reduction in healthcare costs and enhancement of patient quality of life further underscore the attractiveness of stem cell applications in wound care. This systematic review explores the clinical utilization of stem cells and stem cell products, providing valuable insights into their role as ancillary methods in treating chronic wounds.
Topics: Humans; Endothelial Cells; Quality of Life; Wound Healing; Pluripotent Stem Cells; Intercellular Signaling Peptides and Proteins; Cytokines; Mesenchymal Stem Cell Transplantation
PubMed: 38474251
DOI: 10.3390/ijms25053006 -
Journal of the American Veterinary... Jun 2024Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little consensus exists on the efficacy of these treatments. The study sought to evaluate the efficacy of PRP and MSC treatments by systematic review and meta-analysis.
METHODS
A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Inclusion criteria required an original, peer-reviewed study where horses were administered MSCs or PRP (or both), and a comparator group was described. Studies were assessed for risk of bias and study quality. Random effects meta-analysis with inverse variance weighting was used to calculate pooled estimates of the ORs for the primary outcomes of return to performance and reinjury.
RESULTS
The search criteria identified 764 unique studies, and 21 studies met the inclusion criteria for the systematic review. Seventeen studies were further assessed for the primary outcomes of return to performance and reinjury rate within a meta-analysis. Meta-analyses revealed no increase in the likelihood of a return to performance with any of the biologic treatments. However, MSCs and MSCs administered concurrently with PRP provide a reduced risk of reinjury.
CLINICAL RELEVANCE
The current study identified a decrease in reinjury rate in horses administered MSCs or a combination of MSCs and PRP for tendinopathy and desmopathy. However, results should be interpreted with consideration of the heterogeneity of findings, poor study quality, and high risk of bias in the majority of studies.
Topics: Animals; Horses; Platelet-Rich Plasma; Tendon Injuries; Ligaments; Horse Diseases; Mesenchymal Stem Cell Transplantation
PubMed: 38471305
DOI: 10.2460/javma.23.12.0723 -
PloS One 2024Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid... (Meta-Analysis)
Meta-Analysis
Modified Mesenchymal stem cell, platelet-rich plasma, and hyaluronic acid intervention in early stage osteoarthritis: A systematic review, meta-analysis, and meta-regression of arthroscopic-guided intra-articular approaches.
BACKGROUND
Mesenchymal stem cells (MSCs) hold promise for osteoarthritis (OA) treatment, potentially enhanced by combining them with platelet-rich plasma (PRP) and hyaluronic acid (HA). This study aimed to assess the synergy of MSCs, PRP, and varying HA doses, and determine optimal MSC sources to treat early-stage OA in the perspective of Lysholm score, VAS Score, KSS score, and WOMAC score.
METHOD
Original articles from 2013 to 2023 were screened from four databases, focusing on clinical trials and randomized controlled trials. The Risk of Bias in Non-randomized Studies-of Interventions (ROB-2) tool evaluated bias, and a PICOS criteria table guided result construction. Revman 5.4 analyzed outcomes such as Lysholm score, VAS score, KSS, WOMAC score, cartilage volume, and defect size using MRI. This systematic review adhered to PRISMA guidelines.
RESULT
Nine studies met the final inclusion criteria. Meta-analysis revealed a significant improvement in Lysholm score (MD: 17.89; 95% CI: 16.01, 19.77; I2 = 0%, P = 0.56), a notable reduction in VAS score (MD: -2.62; 95% CI: -2.83, -2.41; I2 = 99%, P < 0.00001), elevated KSS (MD: 29.59; 95% CI: 27.66, 31.52; I2 = 95%, P < 0.0001), and reduced WOMAC score (MD: -12.38; 95% CI: -13.75, -11.01; I2 = 99%, P < 0.0001).
CONCLUSIONS
Arthroscopic guided high-dose subchondral application of primary cultured synovial MSCs in popliteal PRP media with HA effectively regenerates cartilage defects and improves clinical outcomes in early-stage osteoarthritis. Clarification of MSC sources and quantities enhances the understanding of this promising treatment modality.
Topics: Humans; Hyaluronic Acid; Viscosupplements; Osteoarthritis, Knee; Injections, Intra-Articular; Platelet-Rich Plasma; Treatment Outcome
PubMed: 38457479
DOI: 10.1371/journal.pone.0295876 -
Frontiers in Public Health 2024Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential toxicity...
INTRODUCTION
Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds.
METHODS
The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers.
RESULTS
740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies.
CONCLUSION
comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].
Topics: Humans; Bandages; Databases, Factual; Ions; Silver; Wound Infection
PubMed: 38450128
DOI: 10.3389/fpubh.2024.1331753 -
Hypertension Research : Official... May 2024Juxtaglomerular cell tumors (JGCTs) or reninoma are rare kidney tumors leading to secondary hypertension, and the non-specific clinical manifestations bring about...
Juxtaglomerular cell tumors (JGCTs) or reninoma are rare kidney tumors leading to secondary hypertension, and the non-specific clinical manifestations bring about challenges to the diagnosis. This study is to summarize the clinical features, laboratory findings, and treatment of JGCTs. The PubMed, EMBASE database, and manual search were utilized to find all cases, and 158 reports containing 261 patients were identified. Data on patients' demographics, clinical features, diagnostic methods, and treatment options were collected and analyzed. JGCTs occurred predominantly in female patients (female to male ratio, 2.1:1). The median age of patients was 25 years (IQR:18-34 years). Hypertension (97.24%) was the cardinal manifestation. Hypokalemia was reported in 78.71% (159/202) of subjects, and normal serum potassium accounted for 20.79% (42/202). In cases with assessed plasma renin activity (PRA) levels, the median PRA was 7.89 times the upper limit of normal (IQR:3.58-14.41), and 3.82% (5/131) of cases in the normal range. Tumors were detected in 97.8% (175/179) computed tomography (CT), 94.7% (72/76) magnetic resonance imaging (MRI), and 81.5% (110/135) ultrasound, respectively. For 250/261 patients undergoing surgical procedures, 89.14% (197/221), 94.94% (150/158), and 100% (131/131) of patients were restored to normal blood pressure, PRA, and serum potassium, respectively. JGCTs are commonly associated with hypertension, hypokalemia, and hyperreninemia, whereas patients with normotension, normokalemia, and PRA should be systematically pursued after drug-elution lasting for 2 weeks. CT and MRI are more sensitive imaging diagnostic methods. The blood pressure and biochemical parameters of most patients returned to normal after surgery.
Topics: Adult; Female; Humans; Male; Young Adult; Hypertension; Juxtaglomerular Apparatus; Kidney Neoplasms; Renin
PubMed: 38438720
DOI: 10.1038/s41440-024-01606-w -
Biomolecules & Biomedicine Feb 2024Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and... (Meta-Analysis)
Meta-Analysis
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72-0.88), 0.80 (95% CI, 0.73-0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR.
PubMed: 38386614
DOI: 10.17305/bb.2024.10049 -
International Journal of Reproductive... Dec 2023Management for pelvic floor disorders needs to be improved. Platelet-rich plasma (PRP) offers an innovative treatment in general medical care to promote cell... (Review)
Review
BACKGROUND
Management for pelvic floor disorders needs to be improved. Platelet-rich plasma (PRP) offers an innovative treatment in general medical care to promote cell regeneration.
OBJECTIVE
This review aims to investigate the role of PRP in pelvic floor disorders.
MATERIALS AND METHODS
6 international databases were accessed using several keywords namely PubMed, Science Direct, Cochrane Library, ProQuest, Google Scholar, and Scopus. The inclusion criteria were articles written in English, published in 10-yr period from 2012 until 2022, and investigated the relevant topic. This systematic review followed PRISMA guideline.
RESULTS
644 articles were found in several databases and 15 articles met the criteria. Management for pelvic floor disorders needs to be improved, but there are still many challenges, such as less effective treatments, risk of recurrence, and postoperative wound healing. PRP offers an innovative treatment in general medical care to promote cell regeneration. A total of 644 articles from the database were found, but 15 studies met the criteria. A total of 600 women with various pelvic floor disorders treated with PRP were analyzed. PRP positively impacts female sexual dysfunction, perineal trauma, vulvovaginal atrophy, stress urinary incontinence, vesicovaginal fistula, perineal rupture, and pelvic organ prolapse. Dosages, preparation techniques, injection techniques, and additive materials are varied. Most studies do not report side effects from the therapy, but the urinary disorder complaints must be paid attention to.
CONCLUSION
PRP can be used to manage pelvic floor disorders. Future studies should clarify and standardize the dose in each case and how to make PRP produce the best results.
PubMed: 38370486
DOI: 10.18502/ijrm.v21i12.15034