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Indian Heart Journal 2023Scant data is available on the efficacy and safety of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) for early and rapid reduction of low-density... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Scant data is available on the efficacy and safety of proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) for early and rapid reduction of low-density lipoprotein cholesterol (LDL-C) within 4-8 weeks of an acute event in patients with acute coronary syndrome (ACS). We undertook this meta-analysis to address this knowledge-gap.
METHODS
Electronic databases were searched for RCTs involving patients with ACS receiving PCSK9i in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in 1-month LDL-C post ACS. Secondary outcomes were to evaluate alterations in other lipid parameters and adverse events.
RESULTS
From initially screened 194 articles, data from 3 studies was analyzed. After 4-weeks therapy, patients receiving PCSK9i had lower LDL-C [MD -0.95 mmol/L (95%CI:-1.51 to -0.40); P = 0.0007; I = 96%, total cholesterol (TC) [MD-1.05 mmol/L (95%CI:-1.83 to -0.27); P = 0.009; I = 94%] and triglycerides (TG) [MD-0.27 mmol/L (95%CI:-0.44 to -0.10); P = 0.002; I = 0%] compared to controls. After 4-8 weeks therapy, patients receiving PCSK9i has lower apolipoprotein B [MD-27.74% (95%CI:-42.59 to -12.89); P = 0.0003; I = 89%] as compared to controls. High density lipoprotein cholesterol (HDL-C) [MD 0.05 mmol/L (95%CI:-0.00-0.11); P = 0.05; I = 0%], lipoprotein(a) [MD-20.63 mmol/L (95%CI:-41.86- 0.59); P = 0.06; I = 54%] and apolipoprotein A1 [MD 0.02 g/L (95%CI:-0.02-0.07); P = 0.32; I = 0%] were comparable between groups. Hospital readmission for ACS was significantly lower in group receiving PCSK9i compared to controls [OR0.25 (95%CI:0.07-0.85); P = 0.03; I = 0%]. Occurrence of cardiac death [OR3.75 (95%CI:0.41-34.22); P = 0.24; I = 0%], serious adverse events [OR0.71 (95% CI:0.13-3.83); P = 0.69; I = 70%] and total adverse events [OR1.01 (95%CI: 0.19-5.30); P = 0.99; I = 92%] was comparable between groups.
CONCLUSION
PCSK9i are highly effective in early reduction of LDL-C along with reduction of early hospital readmissions post-ACS.
Topics: Humans; Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, HDL; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Proprotein Convertase 9; Subtilisins
PubMed: 37777180
DOI: 10.1016/j.ihj.2023.09.005 -
Academic Radiology Feb 2024Despite the acknowledged diagnostic detection rate of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer, little is... (Meta-Analysis)
Meta-Analysis Review
Detection Rate of PSMA PET Using Different Ligands in Men with Biochemical Recurrent Prostate Cancer Following Radical Treatment: A Systematic Review and Meta-analysis of Prospective Studies.
BACKGROUND
Despite the acknowledged diagnostic detection rate of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging in prostate cancer, little is known about the quality of evidence, particularly focusing on prospective studies. Most systematic reviews are based on retrospective reports.
RATIONALE AND OBJECTIVES
To conduct systematic review and meta-analysis of prospective studies reporting the diagnostic detection rate of PSMA PET (computed tomography (CT) and MR) for the detection of biochemically recurrent metastatic prostate cancer.
MATERIALS AND METHODS
We systematically searched PubMed, MEDLINE, Embase, and Scopus, from database until March 1, 2023 for randomized controlled trials and prospective studies using PSMA PET imaging in prostate cancer. The primary endpoint was to assess diagnostic detection rate of PSMA PET imaging in the detection of recurrent prostate cancer in men with biochemical relapse following radical treatment. We calculated the pooled overall diagnostic detection rate with 95% CI using a random-effects model and assessed the heterogeneity between the studies including risk of biases estimation.
RESULTS
A total of 6800 patients from 32 articles were included in this study. The overall detection rate of PSMA PET for prostate cancer was 0.67 (95% CI, 0.63, 0.71). For histologically confirmed lymph nodes, the PPV from 13 prospective studies containing 1496 patients was 0.96 (95% CI, 0.93, 0.99). We performed a subgroup analysis of PSMA PET detection rates according to categorically grouped Prostate Specific Antigen (PSA) values of 0-0.5, 0.5-1.0, 1.0-2.0, and >2.0 ng/ml and obtained detection rates of 0.44, 0.63, 0.82, and 0.94, respectively. The detection rate of 18F PSMA was better in men with a PSA between 1 ng/ml and 2 ng/ml in comparison to 68Ga PSMA (0.91 with 95% CI 0.81-0.99 vs. 0.79 with 95% CI 0.73, 0.85).
CONCLUSION
PSMA PET imaging provides a good detection rate for the metastatic recurrence of prostate cancer in men with biochemical relapse following radical treatment. The detection rate improves significantly above a serum PSA value of 1 ng/ml. The diagnostic detection rate of 18F-PSMA is best at PSA values between 1 and 2 ng/ml, in comparison to 68Ga PSMA. This conclusion is heavily biased, further research needs to focus on better methodology to minimize the risk of biases.
Topics: Male; Humans; Prostate-Specific Antigen; Prospective Studies; Retrospective Studies; Neoplasm Recurrence, Local; Prostatic Neoplasms; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography; Recurrence
PubMed: 37770370
DOI: 10.1016/j.acra.2023.08.044 -
International Journal of Stroke :... Mar 2024Telestroke systems operate through remote communication, providing distant stroke evaluation through expert healthcare providers. The aim of this study was to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Telestroke systems operate through remote communication, providing distant stroke evaluation through expert healthcare providers. The aim of this study was to assess whether the implementation of a telestroke system influenced stroke treatment outcomes in acute ischemic stroke (AIS) patients compared with conventional in-person treatment.
AIMS
The study group evaluated multiple studies from electronic databases, comparing telemedicine (TM) and non-telemedicine (NTM) AIS patients between 1999 and 2022. We aimed to evaluate baseline characteristics, critical treatment times, and clinical outcomes.
SUMMARY OF REVIEW
A total of 12,540 AIS patients were included in our study with 7936 (63.9%) thrombolyzed patients. Of the thrombolyzed patients, 4150 (51.7%) were treated with TM, while 3873 (48.3%) were not. The mean age of TM and NTM cohorts was 70.45 ± 4.68 and 70.42 ± 4.63, respectively (p > 0.05). Mean National Institute of Health Stroke Scale scores were comparable, with the TM group reporting a non-significantly higher mean (11.89 ± 3.29.6 vs. 11.13 ± 3.65, p > 0.05). No significant difference in outcomes was found for symptoms onset-to-intravenous tissue plasminogen activator (ivtPA) times (144.09 ± 18.87 vs. 147.18 ± 25.97, p = 0.632) and door-to-needle times (73.03 ± 20.04 vs. 65.91 ± 25.96, p = 0.321). Modified Rankin scale scores (0-2) were evaluated, and no significant difference was detected between cohorts (odds ratio (OR): 1.06, 95% confidence interval (CI): 0.89-1.29, p = 0.500). Outcomes did not indicate any significance between both cohorts for 90-day mortality (OR: 1.16, 95% CI: 0.94-1.43, p = 0.17) or symptomatic intracranial hemorrhage (OR: 0.99, 95% CI: 0.73-1.34, p = 0.93). Results between groups were also non-significant when analyzing the rate of thrombolysis with ivtPA (30.86%± 30.7 vs. 20.5%± 18.6, p = 0.372) and endovascular mechanical thrombectomy (11.8%± 11.7 vs. 18.7%± 18.9, p = 0.508).
CONCLUSION
The use of telestroke in the treatment of AIS patients is safe with minimal non-significant differences in long-term outcomes and rates of thrombolysis compared with face-to-face treatment. Further studies comparing the different methods of TM are needed to assess the efficacy of TM in stroke treatment.
Topics: Humans; Tissue Plasminogen Activator; Stroke; Fibrinolytic Agents; Ischemic Stroke; Thrombolytic Therapy; Treatment Outcome; Brain Ischemia
PubMed: 37752674
DOI: 10.1177/17474930231206066 -
Journal of Trace Elements in Medicine... Dec 2023Iron homeostasis disturbance has been suggested to play a role in the pathology of Alzheimer's disease (AD). Systemic iron levels are regulated by iron-related proteins,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Iron homeostasis disturbance has been suggested to play a role in the pathology of Alzheimer's disease (AD). Systemic iron levels are regulated by iron-related proteins, such as ferritin and transferrin. This meta-analysis was established to evaluate iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, hepcidin) in cerebrospinal fluid (CSF) and blood samples of AD patients compared with those in healthy controls (HCs).
METHODS
Iron and iron-related proteins in Alzheimer's disease was systematically searched within five databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus) up to October 23, 2022. Fifty-four studies (with data for 5105 participants: 2174 AD patients and 2931 HCs) were included in this meta-analysis. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), applying Stata 14.0 software.
RESULTS
Decreased iron in blood and increased ferritin in CSF were found in AD patients compared with the levels in HCs. AD patients also exhibited lower lactoferrin in serum. Other variables (iron in CSF, ferritin in blood, transferrin in CSF/blood, haptoglobin in CSF/blood, and hepcidin in blood) did not differ between the groups.
CONCLUSION
This meta-analysis indicated that iron and iron-related proteins were associated with the risk of AD, suggesting the value of further exploration of iron imbalance in AD using biofluids.
Topics: Humans; Alzheimer Disease; Iron; Hepcidins; Haptoglobins; Lactoferrin; Ferritins; Transferrin
PubMed: 37734209
DOI: 10.1016/j.jtemb.2023.127304 -
Journal of Ethnopharmacology Jan 2024Stroke is one of the leading causes of death and disability. The only FDA-approved therapy for treating stroke is tissue plasminogen activator (tPA), exhibiting a short...
ETHNOPHARMACOLOGICAL RELEVANCE
Stroke is one of the leading causes of death and disability. The only FDA-approved therapy for treating stroke is tissue plasminogen activator (tPA), exhibiting a short therapeutic window. Due to this reason, only a small number of patients can be benefitted in this critical period. In addition, the use of endovascular interventions may reverse vessel occlusion more effectively and thus help further improve outcomes in experimental stroke. During recovery of blood flow after ischemia, patients experience cognitive, behavioral, affective, emotional, and electrophysiological changes. Therefore, it became the need for an hour to discover a novel strategy for managing stroke. The drug discovery process has focused on developing herbal medicines with neuroprotective effects via modulating neuroplasticity.
AIM OF THE STUDY
We gather and highlight the most essential traditional understanding of therapeutic plants and their efficacy in cerebral ischemia-reperfusion injury. In addition, we provide a concise summary and explanation of herbal drugs and their role in improving neuroplasticity. We review the pharmacological activity of polyherbal formulations produced from some of the most frequently referenced botanicals for the treatment of cerebral ischemia damage.
MATERIALS AND METHODS
A systematic literature review of bentham, scopus, pubmed, medline, and embase (elsevier) databases was carried out with the help of the keywords like neuroplasticity, herbal drugs, neural progenitor cells, neuroprotection, stem cells. The review was conducted using the above keywords to understand the therapeutic and mechanistic role of herbal neuroprotective agents on neuroplasticity in cerebral ischemic-reperfusion injury.
RESULTS
Neuroplasticity emerged as an alternative to improve recovery and management after cerebral ischemic reperfusion injury. Neuroplasticity is a physiological process throughout one's life in response to any stimuli and environment. Traditional herbal medicines have been established as an adjuvant to stroke therapy since they were used from ancient times and provided promising effects as an adjuvant to experimental stroke. The plants and phytochemicals such as Curcuma longa L., Moringa oliefera Lam, Panax ginseng C.A. Mey., and Rehmannia glutinosa (Gaertn.) DC., etc., have shown promising effects in improving neuroplasticity after experimental stroke. Such effects occur by modulation of various molecular signalling pathways, including PI3K/Akt, BDNF/CREB, JAK/STAT, HIF-1α/VEGF, etc. CONCLUSIONS: Here, we gave a perspective on plant species that have shown neuroprotective effects and can show promising results in promoting neuroplasticity with specific targets after cerebral ischemic reperfusion injury. In this review, we provide the complete detail of studies conducted on the role of herbal drugs in improving neuroplasticity and the signaling pathway involved in the recovery and management of experimental stroke.
Topics: Humans; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Plant Extracts; Reperfusion Injury; Stroke; Tissue Plasminogen Activator
PubMed: 37717842
DOI: 10.1016/j.jep.2023.117153 -
Clinical Neurology and Neurosurgery Oct 2023Alteplase is the standard medical therapy for acute ischemic stroke (AIS) patients who present within 4.5 h of symptom onset. Tenecteplase is a modified alteplase... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alteplase is the standard medical therapy for acute ischemic stroke (AIS) patients who present within 4.5 h of symptom onset. Tenecteplase is a modified alteplase variant with pharmacological and practical advantages over alteplase. Many trials have investigated the efficacy and safety of tenecteplase against alteplase. This systematic review and meta-analysis aimed to compare the efficacy and safety of tenecteplase to alteplase across randomized controlled trials.
METHOD
Medline, Embase, and Cochrane CENTRAL were used to search the related articles until February 20, 2023. Randomized controlled trials (RCTs) that compared the effectiveness and safety of tenecteplase against alteplase for AIS patients were included. Screening, risk of bias assessment, and data extraction were performed following PRISMA guidelines. Data were pooled using a random-effect model.
RESULTS
Ten RCTs were included, with a total of 5123 patients. There was no significant difference between the two interventions in modified rankin scale 0-1 (mRS 0-1) (RR= 1.04, 95% CI [0.99-1.10], P = 0.11, I =0%) and early neurological improvement (RR= 1.06, 95% CI [0.97-1.15], P = 0.21, I =35). There was no difference in the rates of symptomatic intracranial hemorrhage (RR= 1.18, 95% CI [0.84-1.65], P = 0.35, I = 0%). Tenecteplase was associated with significantly higher complete recanalization rate compared to alteplase (RR= 1.17, 95% CI [1.00-1.36], P = 0.05, I =0%). For large vessel occlusion (LVO) patients assigned to tenecteplase, there was a significant improvement in mRS 0-1 (RR= 1.28, 95% CI [1.07-1.52], P = 0.006, I =0%).
CONCLUSION
Based on our meta-analysis, tenecteplase has similar efficacy and safety to alteplase, with a more promising effect in patients with LVO.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Stroke; Brain Ischemia; Randomized Controlled Trials as Topic; Ischemic Stroke; Treatment Outcome
PubMed: 37713743
DOI: 10.1016/j.clineuro.2023.107961 -
JPMA. the Journal of the Pakistan... Aug 2023To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine...
OBJECTIVE
To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma.
METHODS
The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters.
RESULTS
Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia.
CONCLUSION
Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen.
PROSPERO REGISTRATION NUMBER
CRD42022334906.
Topics: Male; Humans; Middle Aged; Aged; Multiple Myeloma; Prostate; Prostatic Neoplasms; Prostate-Specific Antigen; Adenocarcinoma
PubMed: 37697762
DOI: 10.47391/JPMA.8068 -
European Journal of Gastroenterology &... Nov 2023Restorative proctocolectomy (RPC) is the most common surgical procedure to restore gastrointestinal continuity after surgical resection of the colon and rectum.... (Meta-Analysis)
Meta-Analysis
Restorative proctocolectomy (RPC) is the most common surgical procedure to restore gastrointestinal continuity after surgical resection of the colon and rectum. Pouchitis is a common complication with several different modalities that can be used to aid diagnosis. This systematic review and meta-analysis aimed at exploring the sensitivity and specificity these diagnostic modalities. The medical literature was searched using MEDLINE, EMBASE and EMBASE classic and PubMed from 1978 to June 2022. We calculated descriptive statistics using sensitivity, specificity, and false-positive rate of the primary studies and also their positive and negative likelihood ratios, and their diagnostic odds ratios. The screen found 5477 records with 13 studies being included. Faecal lactoferrin was found to have the highest pooled sensitivity and specificity of 98% and 88% respectively with imaging modalities coming in second and faecal calprotectin third with pooled sensitivities and specificities of 87% and 79% and 74% and 81% respectively. Faecal biomarkers particularly lactoferrin and imaging modalities may have an important role to play in diagnosing pouchitis. Importantly due to delays in availability of pouchoscopy, our data supports early ordering of these tests to help delineate from other causes. Further studies are required with larger cohort sizes to further validate these tests.
Topics: Humans; Pouchitis; Lactoferrin; Proctocolectomy, Restorative; Sensitivity and Specificity; Feces
PubMed: 37695613
DOI: 10.1097/MEG.0000000000002638 -
The Turkish Journal of Pediatrics 2023Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been... (Review)
Review
BACKGROUND
Anemia is a common nutritional problem in children, especially those under five. Lactoferrin (Lf) as a supplement in treating iron deficiency anemia (IDA) has been studied, but its results in children have not been reviewed. This review aims to evaluate the effect of lactoferrin on children with IDA.
METHODS
PubMed, ProQuest, EBSCO and Ovid databases were searched using a variation of keywords: lactoferrin, anemia, and children. The literature selected must be clinical trial-based in design. The years of the studies published were limited to 2012 and 2022.
RESULTS
Eleven studies were included in the final systematic review, consisting of 10 randomized controlled trials (RCTs) and 1 non-randomized trial. Serum ferritin (SF) and hemoglobin (Hb) were found to be increased in groups treated with Lf or a combination of Lf and elemental iron compared to iron only or placebo supplementation. Adverse events such as constipation, vomiting, anorexia, and abdominal pain were found; particularly, a significant decrease in constipation is seen in Lf-treated groups.
CONCLUSIONS
This study supports Lf as a superior treatment for IDA in children regarding the improvement in hematological and iron indices and fewer adverse effects.
Topics: Child; Humans; Abdominal Pain; Anemia, Iron-Deficiency; Constipation; Iron; Lactoferrin
PubMed: 37661669
DOI: 10.24953/turkjped.2022.670 -
Immunity, Inflammation and Disease Aug 2023Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lactoferrin is a versatile protein with important modulatory functions in inflammation and immune response. This glycoprotein can bind and sequester iron and LPS, thereby intervening in certain signaling pathways and biological processes. In the present meta-analysis, we aimed to pool experimental data regarding the immunomodulatory effects of lactoferrin and its derived peptides on the NF-κB signaling pathway.
MATERIALS
We searched PubMed, Google Scholar, and Web of Science databases and obtained all related articles published before April 2022. Finally, 25 eligible studies were selected, and their reports were analyzed.
METHODS
We used Review Manager Version 5.2 to compute the standardized mean difference (SMD) and its 95% confidence interval. In addition, the source of heterogeneity was explored using meta-regression and sensitivity analysis. The symmetry of the funnel plot and Egger's test were also used to evaluate publication bias utilizing Comprehensive Meta-Analysis Version 2.
RESULTS
Comparing the group of cells and animals exposed to lipopolysaccharide alone with the group that received pretreatment with lactoferrin and its derivatives, we observed significant reductions in TNF-α, IL-1 beta, and IL-6 levels by 8.73 pg/mL, 2.21 pg/mL, and 3.24 pg/mL, respectively, in the second group. Additionally, IKK-β, p-IκB, and NF-κB (p65) levels were significantly lower by 7.37-fold, 15.02-fold, and 3.88-fold, respectively, in various cells and tissues.
CONCLUSION
Based on the results of this meta-analysis, lactoferrin and its derived peptides can be considered potent prophylactic and therapeutic candidates against inflammation-associated diseases by targeting the NF-kB pathway.
Topics: Animals; NF-kappa B; Lactoferrin; Signal Transduction; Peptides; Inflammation; Lipopolysaccharides; Immunity
PubMed: 37647433
DOI: 10.1002/iid3.972