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Iranian Journal of Public Health Jan 2024Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on... (Review)
Review
BACKGROUND
Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.
METHODS
The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.
RESULTS
Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.
CONCLUSION
Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.
PubMed: 38694865
DOI: 10.18502/ijph.v53i1.14686 -
Annals of Hematology Jun 2024Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between... (Meta-Analysis)
Meta-Analysis
Janus kinase 2 (JAK2) V617F mutation is present in most patients with polycythemia vera (PV). One persistently puzzling aspect unresolved is the association between JAK2V617F allele burden (also known as variant allele frequency) and the relevant clinical characteristics. Numerous studies have reported associations between allele burden and both hematologic and clinical features. While there are strong indications linking high allele burden in PV patients with symptoms and clinical characteristics, not all associations are definitive, and disparate and contradictory findings have been reported. Hence, this study aimed to synthesize existing data from the literature to better understand the association between JAK2V617F allele burden and relevant clinical correlates. Out of the 1,851 studies identified, 39 studies provided evidence related to the association between JAK2V617F allele burden and clinical correlates, and 21 studies were included in meta-analyses. Meta-analyses of correlation demonstrated that leucocyte and erythrocyte counts were significantly and positively correlated with JAK2V617F allele burden, whereas platelet count was not. Meta-analyses of standardized mean difference demonstrated that leucocyte and hematocrit were significantly higher in patients with higher JAK2V617F allele burden, whereas platelet count was significantly lower. Meta-analyses of odds ratio demonstrated that patients who had higher JAK2V617F allele burden had a significantly greater odds ratio for developing pruritus, splenomegaly, thrombosis, myelofibrosis, and acute myeloid leukemia. Our study integrates data from approximately 5,462 patients, contributing insights into the association between JAK2V617F allele burden and various hematological parameters, symptomatic manifestations, and complications. However, varied methods of data presentation and statistical analyses prevented the execution of high-quality meta-analyses.
Topics: Polycythemia Vera; Janus Kinase 2; Humans; Alleles; Gene Frequency; Amino Acid Substitution; Mutation, Missense
PubMed: 38652240
DOI: 10.1007/s00277-024-05754-4 -
Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2 -
International Journal of Molecular... Mar 2024Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22...
Chronic myeloid leukemia is a multistep, multi-lineage myeloproliferative disease that originates from a translocation event between chromosome 9 and chromosome 22 within the hematopoietic stem cell compartment. The resultant fusion protein BCR::ABL1 is a constitutively active tyrosine kinase that can phosphorylate multiple downstream signaling molecules to promote cellular survival and inhibit apoptosis. Currently, tyrosine kinase inhibitors (TKIs), which impair ABL1 kinase activity by preventing ATP entry, are widely used as a successful therapeutic in CML treatment. However, disease relapses and the emergence of resistant clones have become a critical issue for CML therapeutics. Two main reasons behind the persisting obstacles to treatment are the acquired mutations in the ABL1 kinase domain and the presence of quiescent CML leukemia stem cells (LSCs) in the bone marrow, both of which can confer resistance to TKI therapy. In this article, we systemically review the structural and molecular properties of the critical domains of BCR::ABL1 and how understanding the essential role of BCR::ABL1 kinase activity has provided a solid foundation for the successful development of molecularly targeted therapy in CML. Comparison of responses and resistance to multiple BCR::ABL1 TKIs in clinical studies and current combination treatment strategies are also extensively discussed in this article.
Topics: Humans; Drug Resistance, Neoplasm; Fusion Proteins, bcr-abl; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Protein Kinase Inhibitors; Signal Transduction
PubMed: 38542279
DOI: 10.3390/ijms25063307 -
Critical Reviews in Oncology/hematology Apr 2024We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and meta-analysis to evaluate outcomes after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in TP53-mutated myelodysplastic syndromes (MDS). A literature search was performed on PubMed, Cochrane, Embase, and Clinicaltrials.gov. After screening 626 articles, eight studies were included. Data were extracted following the PRISMA guidelines and analyzed using the meta-package by Schwarzer et al. We analyzed 540 patients. The pooled median 3 (1-5) year overall survival was 21% (95% CI 0.08-0.37, I2=91%, n=540). The pooled relapse rate was 58.9% (95% CI 0.38-0.77, I2=93%, n=487) at a median of 1.75 (1-3) years. The pooled 4-year progression- free survival was 34.8% (95% CI 0.15-0.57, I2=72%, n=105). Outcomes of Allo-HSCT for TP53-mutated MDS patients remain poor, with 21% OS at three years; however, Allo-HSCT confers a survival advantage as compared to non-transplant palliative therapies. Our findings suggest the need to explore novel therapeutic agents in prospective clinical trials.
Topics: Humans; Prospective Studies; Myelodysplastic Syndromes; Hematopoietic Stem Cell Transplantation; Progression-Free Survival; Transplantation Conditioning; Tumor Suppressor Protein p53
PubMed: 38423375
DOI: 10.1016/j.critrevonc.2024.104310 -
Heliyon Feb 2024Diabetic ulcers (DUs) typically occur in patients with vascular diseases and diabetes. Extracellular vesicles secreted by bone marrow-derived stem cells (BMSC-EVs)...
Extracellular vesicles secreted by bone marrow stem cells mediate angiogenesis for the treatment of diabetic ulcers: A systematic review and meta-analysis of preclinical studies.
BACKGROUND
Diabetic ulcers (DUs) typically occur in patients with vascular diseases and diabetes. Extracellular vesicles secreted by bone marrow-derived stem cells (BMSC-EVs) represent a cell-free therapy that has emerged as a promising alternative for treating DU, especially due to significant advancements in the understanding of their role in promoting angiogenesis; however, their application in DU treatment remains in the preclinical stage, and their effectiveness is still uncertain. Therefore, we conducted this meta-analysis to evaluate the therapeutic efficacy of BMSC-EVs in treating DU and to expedite the clinical translation of BMSC-EV therapy for DU.
METHODS
We conducted a comprehensive search of PubMed, Cochrane Library, MEDLINE, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, and our self-constructed database of Chinese Biomedical Literature up to May 2023 to identify preclinical studies related to the therapeutic use of extracellular vesicles secreted by bone marrow-derived stem cells for treating diabetic ulcers. Outcome measures included wound healing rate, neovascularization density, a-sma, and CD31. RevMan 5 software was employed for all statistical analyses.
RESULTS
In this meta-analysis, a total of 11 studies involving 103 animals were identified. The pooled analysis indicated that BMSC-EV treatment showed a superior wound healing rate compared to that of the control group (SMD = 1.06, 95% CI [0.52, 1.60], P = 0.0001). In the subgroup analysis, EV combined with new materials or drug therapy performed better than the sole injection of extracellular vesicles (SMD = 1.85, 95% CI [0.87, 2.82], P < 0.00001). BMSC-EV treatment also resulted in a higher number of neovascular structures compared to the control group(SMD = 5.80, 95% CI[0.89,10.71], P = 0.006). In the subgroup analysis, EV combined therapy showed a significant difference in the number of blood vessels compared to the sole injection of extracellular vesicles (SMD = 4.90, 95% CI[2.64,7.15], P < 0.00001). However, BMSCs-EV treatment did not demonstrate any statistically significant difference in the angiogenesis-related indicators CD31 and α-SMA compared to the control group (SMD = 1.61, 95% CI[-0.51,3.74], P = 0.14).
CONCLUSION
According to the current meta-analysis, BMSC-EV therapy can enhance the healing of diabetic ulcers and promote wound angiogenesis, particularly when used in combination with novel dressings or other drugs, which further accelerates the healing process of diabetic ulcers. To establish the most effective parameters for EV treatment in diabetic ulcers, future research should promptly progress into clinical trials.
PubMed: 38390125
DOI: 10.1016/j.heliyon.2024.e25762 -
BMC Nephrology Jan 2024It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is crucial to identify patients with monoclonal gammopathy of renal significance (MGRS) from those without MGRS but with monoclonal gammopathy and concomitant kidney diseases. However, there have been few studies with large sample sizes, and their findings were inconsistent. This study aimed to conduct a meta-analysis of MGRS to describe the general characteristics of MGRS and its predictive factors.
METHODS
Cohort or case-control studies published through December 2022 and related to clinicopathological features of MGRS were retrieved from the PubMed, Cochrane Library, Web of Science, Scopus, and Embase databases. Two researchers searched for studies that met the inclusion criteria. In the univariate analysis, fixed- or random- effects models were used to obtain pooled estimates of the weighted mean difference (WMD) and odds ratio (OR) for risk factors. In the multivariate analysis, the ORs of the independent risk factors from each study were pooled after transforming the original estimates.
RESULTS
The meta-analysis included six studies. Univariate analysis showed that the following variables were statistically significant in MGRS: age (WMD = 1.78, 95%CI 0.21-3.35), hypertension (OR = 0.54, 95%CI 0.4-0.73), diabetes (OR = 0.42, 95%CI 0.29-0.59), albumin (WMD = - 0.26, 95%CI - 0.38--0.14), urinary protein level (WMD = 0.76, 95%CI 0.31-1.2), urinary protein ≥ 1.5 g/d (OR = 1.98, 95%CI 1.46-2.68), lambda-chain value (WMD = 29.02, 95%CI 16.55-41.49), abnormal free light-chain ratio (OR = 4.16, 95%CI 1.65-10.47), bone marrow puncture rate (OR = 5.11, 95% CI 1.31-19.95), and abnormal bone marrow outcome rate (OR = 9.63, 95%CI 1.98-46.88). Multivariate analysis showed urinary protein ≥ 1.5 g/d (OR = 2.80, 95%CI 1.53-5.15) and an abnormal free light-chain ratio (OR = 6.98, 95%CI 4.10-11.91) were associated with predictors of MGRS.
CONCLUSIONS
Compared with non-MGRS patients with monoclonal gammopathy and concomitant kidney diseases, patients with MGRS were older, had fewer underlying diseases, more urinary protein, more abnormal free light-chain ratio, and more abnormal bone marrow results. Urinary protein ≥ 1.5 g/d and an abnormal free light-chain ratio were independent risk factors for MGRS.
Topics: Humans; Paraproteinemias; Kidney; Monoclonal Gammopathy of Undetermined Significance; Kidney Diseases; Immunoglobulin Light Chains
PubMed: 38229028
DOI: 10.1186/s12882-024-03458-5 -
Medicine Jan 2024This systematic literature review and meta-analysis aimed to assess the accuracy, sensitivity, and specificity of dual-energy computed tomography (DECT) of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic literature review and meta-analysis aimed to assess the accuracy, sensitivity, and specificity of dual-energy computed tomography (DECT) of the sacroiliac joint. Bone marrow edema (BME) of the sacroiliac joint is an early manifestation of some diseases, such as ankylosing spondylitis, and is usually examined by nuclear magnetic resonance imaging (MRI); however, MRI can be intolerable for some patients; hence, numerous studies have analyzed DECT examinations.
METHODS
We searched PUBMED, CNKI, and EMBASE in 2023 for articles containing the following terms (DECT) or (DE-CT) or (dual-energy CT) or "dual-energy CT" or (dual-energy computed tomography) and ((sacroiliac joint) or (ankylosing spondylitis) or (sacroiliac arthritis) or (sacroiliitis)). An initial search identified 444 articles, of which 7 met the criteria. Data were extracted to calculate the sensitivity, specificity, and diagnostic odds for analysis using R software.
RESULTS
Out of 291 patients and 577 sacroiliac joints, 429 (74.35%) exhibited BME. All studies used magnetic resonance as the control group. The overall sensitivity and specificity of DECT were 79%, and 92%, respectively, with positive prediction rate of 92.55% and negative prediction rate of 83.73%.
CONCLUSION
DECT appears to be a promising diagnostic tool for detecting BME in the sacroiliac joint and can be used as an alternative examination method for patients in whom MRI is contraindicated.
Topics: Humans; Sacroiliac Joint; Spondylitis, Ankylosing; Bone Marrow; Edema; Tomography
PubMed: 38181261
DOI: 10.1097/MD.0000000000036708 -
Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Revista Brasileira de Parasitologia... 2023To compare the sensitivity of conjunctival swab (CS) and conventional samples (blood, spleen, liver, lymphoid and cutaneous tissue) in the diagnosis of canine visceral... (Meta-Analysis)
Meta-Analysis
To compare the sensitivity of conjunctival swab (CS) and conventional samples (blood, spleen, liver, lymphoid and cutaneous tissue) in the diagnosis of canine visceral leishmaniasis (CVL) by polymerase chain reaction (PCR), a systematic review and meta-analysis was carried out using PubMed, Science Direct, Scopus, Web of Science, VHL/BVS (Virtual Health Library), CAPES, and Scielo databases. Articles published from 2002 to 2022 were considered and the review was updated in Jul 2023. From the total of 371 identified studies, 8 met all the eligibility criteria and were included in this review. Data from 658 CVL-positive dogs and 2541 PCR results were considered. Using a random effect model, data on the sensitivity of the test was compared between intervention (CS samples) and comparison (all the other samples) groups. Overall, the use of CS in the PCR diagnosis of CVL produced 12% higher sensitivity (p=0.013) in the test than all the other samples in combination. The animals' clinical condition did not influence (p>0.142) this overall result. However, when CS was individually compared to each of the conventional samples, the consistent result was observed (p=0.012) only in the CS versus bone marrow comparison. Given their rapid acquisition, minimal invasiveness, and lower cost relative to conventional samples, CS samples present a promising alternative for the molecular diagnosis of CVL.
Topics: Animals; Dogs; Dog Diseases; Leishmaniasis, Visceral; Polymerase Chain Reaction; Specimen Handling
PubMed: 38018627
DOI: 10.1590/S1984-29612023063