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Frontiers in Pharmacology 2024FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3...
FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration () in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life () range was highly variable, from 6.8 to 151.8 h. FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.
PubMed: 38828446
DOI: 10.3389/fphar.2024.1294668 -
International Journal of Chronic... 2024Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology.
RESEARCH METHODS
Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed.
RESULTS
A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure.
CONCLUSION
This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Drugs, Chinese Herbal; Network Pharmacology; Treatment Outcome; Randomized Controlled Trials as Topic; Lung; Anti-Inflammatory Agents; Middle Aged; Male; Aged; Female; Injections
PubMed: 38826697
DOI: 10.2147/COPD.S442281 -
Academic Emergency Medicine : Official... Jun 2024Emergency department (ED) crowding has repercussions on acute care, contributing to prolonged wait times, length of stay, and left without being seen (LWBS). These... (Review)
Review
BACKGROUND
Emergency department (ED) crowding has repercussions on acute care, contributing to prolonged wait times, length of stay, and left without being seen (LWBS). These indicators are regarded as systemic shortcomings, reflecting a failure to provide equitable and accessible acute care. The objective was to evaluate the effectiveness of interventions aimed at improving ED care delivery indicators.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing ED interventions aimed at reducing key metrics of time to provider (TTP), time to disposition (TTD), and LWBS. We excluded disease-specific trials (e.g., stroke). We used Cochrane's revised tool to assess the risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations to rate the quality of evidence. The meta-analysis was performed using a random-effects model and Cochrane Q test for heterogeneity. Data were summarized as means (±SD) for continuous variables and risk ratios (RR) with 95% confidence intervals (CIs).
RESULTS
We searched MEDLINE, EMBASE, and other major databases. A total of 1850 references were scanned and 20 RCTs were selected for inclusion. The trials reported at least one of the three outcomes of TTD, TTP, or LWBS. Most interventions focused on triage liaison physician and point-of-care (POC) testing. Others included upfront expedited workup (ordering tests before full evaluation by a provider), scribes, triage kiosks, and sending notifications to consultants or residents. POC testing decreased TTD by an average of 5-96 min (high heterogeneity) but slightly increased TTP by a mean difference of 2 min (95% CI 0.6-4 min). Utilizing a triage liaison physician reduced TTD by 28 min (95% CI 19-37 min; moderate-quality evidence) and was more effective in reducing LWBS than routine triage (RR 0.76, 95% CI 0.66-0.88; moderate quality).
CONCLUSIONS
Operational strategies such as POC testing and triage liaison physicians could mitigate the impact of ED crowding and appear to be effective. The current evidence supports these strategies when tailored to the appropriate practice environment.
PubMed: 38826092
DOI: 10.1111/acem.14946 -
Phytomedicine : International Journal... Jul 2024Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of... (Review)
Review
BACKGROUND
Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases.
PURPOSE
This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases.
STUDY DESIGN AND METHODS
We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as "ferroptosis","respiratory diseases","chronic obstructive pulmonary disease","bronchial asthma","acute lung injury","pulmonary fibrosis","lung cancer","traditional Chinese medicine","traditional Chinese medicine compound","monomer", and "natural product" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review).
RESULTS
TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1.
CONCLUSION
TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.
Topics: Ferroptosis; Humans; Drugs, Chinese Herbal; Animals; Signal Transduction; Acute Lung Injury; Medicine, Chinese Traditional; Respiratory Tract Diseases; Reactive Oxygen Species; Pulmonary Fibrosis
PubMed: 38824825
DOI: 10.1016/j.phymed.2024.155738 -
World Journal of Cardiology May 2024In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a...
BACKGROUND
In severe cases of coronary artery disease, percutaneous coronary intervention provide promising results. The stent used could be a drug-eluting stent (DES) or a titanium-nitride-oxide coated stent (TiNOS).
AIM
To compare the 5-year effectiveness and safety of the two stent types.
METHODS
The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines, and PubMed/MEDLINE, Scopus, and Cochrane Central were searched from inception till August 2023. Primary outcomes were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI), cardiac death or MI, and ischemia-driven total lesion revascularization (ID-TLR).
RESULTS
Four randomized controlled trials (RCT), which analyzed a sum total of 3045 patients with acute coronary syndrome (ACS) after a median follow-up time of 5 years were included. Though statistically insignificant, an increase in the ID-TLR was observed in patients receiving TiNOSs DESs. In addition, MI, cardiac death and MI, and definite stent thrombosis (DST) were significantly decreased in the TiNOS arm. Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI (NSTEMI) as a statistically significant covariate in the outcome of MACE.
CONCLUSION
TiNOS was found to be superior to DES in terms of MI, cardiac death or MI, and DST outcomes, however, the effect of the two stent types on ID-TLR and MACE was not significant. A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.
PubMed: 38817643
DOI: 10.4330/wjc.v16.i5.293 -
Cureus Apr 2024Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood... (Review)
Review
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.
PubMed: 38817489
DOI: 10.7759/cureus.59390 -
PLoS Neglected Tropical Diseases May 2024Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver...
Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver and lungs. Although the heart is affected in only 0.02-2% of all CE cases, a considerable number of cases have been, and continue to be, published. However, due to the rare occurrence of cardiac CE and the resulting lack of clinical trials, knowledge about various aspects of the disease remains limited. To obtain a clearer picture of anatomical, clinical, diagnostic as well as therapeutic aspects of cardiac CE, we systematically reviewed the literature published between 1965 and 2022. The anatomical pattern of the affected cardiac structures follows the extension of the supplying capillary bed. The majority of patients (82.7%) are symptomatic and present with prolonged non-specific symptoms such as dyspnoea, chest pain and palpitations. Acute complications generally derive from cyst rupture, occur in 18.3% of cases and manifest as embolism, pericardial tamponade, or anaphylactic reaction in 83.2%, 17.8% and 10.9% of these cases, respectively. As for CE cysts localized in other organs, the diagnosis of cardiac CE is made by imaging. Serology plays a minor role due to its limited sensitivity. Unlike abdominal CE cysts, cardiac CE cysts are usually resected independent of their stage (active/inactive), because their presence impairs cardiac performance and carries the risk of long-term sequelae. More than 80% of patients are treated with a single surgical intervention. We found a disease-related case fatality rate of 11.1%. Since local recurrence was reported up to 108 months and secondary CE up to 72 months after surgery, patients should be followed up for a minimum of 10 years.
Topics: Humans; Echinococcosis; Animals; Heart Diseases; Echinococcus granulosus; Heart
PubMed: 38814859
DOI: 10.1371/journal.pntd.0012183 -
Frontiers in Pain Research (Lausanne,... 2024Post-acute COVID-19 syndrome or "long COVID" affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent...
BACKGROUND AND OBJECTIVES
Post-acute COVID-19 syndrome or "long COVID" affects patients even after the recovery from Covid infection in various ways. Persistent headache or New Daily Persistent Headache (NDPH) is one of such symptoms. In this review, we will discuss about the case-reports of post covid-19 headache- NDPH phenotype both after and in the course of COVID-19 infection.
METHODS
Case reports/studies talked about patients having NDPH around the disease either immediately or late post COVID were included. Data was taken from the source and synthesised on a qualitative basis.
RESULTS
Literature search showed 3,538 articles, out of which 12 were screened as per the eligibility criteria and finally, 4 case reports on NDPH and Covid-19 were chosen for analysis from the database and by human search. All case reports justify the criteria for acceptability in quality for this systematic review.
CONCLUSION
NDPH in and around Covid 19 infection is something that is currently an ingenious debated topic in the scientific community. More case studies should be written and published on the same subject so that a large systematic review could be conducted.
TRIAL REGISTRATION INFORMATION
The review is registered in Prospero with no. (CRD42022354912).
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42022354912).
PubMed: 38808005
DOI: 10.3389/fpain.2024.1376506 -
Journal of Family & Reproductive Health Dec 2023Multiple sclerosis is an autoimmune disease of central nervous system (CNS). There are a few articles studying the risk factors of developing MS in men. Male infertility... (Review)
Review
OBJECTIVE
Multiple sclerosis is an autoimmune disease of central nervous system (CNS). There are a few articles studying the risk factors of developing MS in men. Male infertility can stem from a range of etiological factors such as genetics or environment. In the context of MS, research suggests a potential link, possibly due to shared immunological and inflammatory mechanisms. Therefore, we designed this study to evaluate the relationship between male infertility and MS development.
MATERIALS AND METHODS
We systematically searched PubMed, Embase, Scopus, web of science, Google scholar and gray literature including references of the references as well as conference papers which were published up to June 2021. The search strategy in PubMed was ("Infertility, Male"[Mesh] OR [Male Infertility] OR [Sterility, Male] OR [Male Sterility] OR [Subfertility, Male] OR [Male Subfertility] OR [Sub-Fertility, Male] OR [Male Sub-Fertility] OR [Sub Fertility, Male]) AND ("Multiple Sclerosis"[Mesh] OR [Sclerosis, Multiple] OR [Sclerosis, disseminated] OR [Disseminated Sclerosis] OR [MS] OR [Multiple Sclerosis, Acute Fulminating]) AND ("Testicular Diseases"[Mesh] OR [Disease, Testicular] OR [Diseases, Testicular] OR [Testicular Disease]) AND ("Multiple Sclerosis"[Mesh] OR [Sclerosis, Multiple] OR [Sclerosis, disseminated] OR [Disseminated Sclerosis] OR [Multiple Sclerosis, Acute Fulminating] OR [MS]).
RESULTS
The literature search revealed 197 articles, after deleting duplicates 109 remained. For the meta-analysis, 3 studies were included. Totally, 2090 MS cases as well as 3895562 healthy subjects were enrolled. One hundred and fourteen infertile men were in MS group and 139716 infertile men were in controls. The pooled OR for male factor infertility and odds of developing MS was1.87 (95% CI: 0.89-3.94) (I=86.1%, P=0.001).
CONCLUSION
The results of this systematic review and meta-analysis show that there is no relationship between male factor infertility and risk of MS.
PubMed: 38807619
DOI: 10.18502/jfrh.v17i4.14590 -
Stroke and Vascular Neurology May 2024Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the...
BACKGROUND
Recently, computational fluid dynamics (CFD) has been used to simulate blood flow of symptomatic intracranial atherosclerotic stenosis (sICAS) and investigate the clinical implications of its haemodynamic features, which were systematically reviewed in this study.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements, we searched PubMed and Embase up to March 2024 and screened for articles reporting clinical implications of haemodynamic parameters in sICAS derived from CFD models.
RESULTS
19 articles met the inclusion criteria, all studies recruiting patients from China. Most studies used CT angiography (CTA) as the source image for vessel segmentation, and generic boundary conditions, rigid vessel wall and Newtonian fluid assumptions for CFD modelling, in patients with 50%-99% sICAS. Pressure and wall shear stress (WSS) were quantified in almost all studies, and the translesional changes in pressure and WSS were usually quantified with a poststenotic to prestenotic pressure ratio (PR) and stenotic-throat to prestenotic WSS ratio (WSSR). Lower PR was associated with more severe stenosis, better leptomeningeal collaterals, prolonged perfusion time and internal borderzone infarcts. Higher WSSR and other WSS measures were associated with positive vessel wall remodelling, regression of luminal stenosis and artery-to-artery embolism. Lower PR and higher WSSR were both associated with the presence and severity of cerebral small vessel disease. Moreover, translesional PR and WSSR were promising predictors for stroke recurrence in medically treated patients with sICAS and outcomes after acute reperfusion therapy, which also provided indicators to assess the effects of stenting treatment on focal haemodynamics.
CONCLUSIONS
CFD is a promising tool in investigating the pathophysiology of ICAS and in risk stratification of patients with sICAS. Future studies are warranted for standardisation of the modelling methods and validation of the simulation results in sICAS, for its wider applications in clinical research and practice.
PubMed: 38806205
DOI: 10.1136/svn-2024-003202