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Clinical Genitourinary Cancer Apr 2024Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole... (Meta-Analysis)
Meta-Analysis Review
Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor and is employed as a second line treatment option for CRPC with an established efficacy profile in patients. The aim of this study is to assess the efficacy of ketoconazole containing regimens for CRPC in terms of prostate specific antigen (PSA) decline rate using a systematic review and meta-analysis. In this review, an electronic search was carried out on PubMed, Cochrane CENTRAL, Scopus, and Google Scholar to find relevant literature. Random effects model was used to assess pooled PSA decline rate and 95% CIs. Publication bias was assessed using the funnel plot symmetry and one-tailed Egger's and Begg's test. In all cases, P-value <.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023466536. A total of 483 articles were retrieved after database searching, out of which 23 studies (having a total of 1315 patients) were included in the review based on prespecified criteria. The PSA decline rate was reported in the 14 observational studies (having 964 patients) and 9 experimental studies (having 351 patients). Pooled results revealed that 48.6% (95% CI 43.1-54.2; P-value <.001; I = 73.24%) of participants achieved more than 50% decline in PSA (602/1315 participants). Sensitivity analysis using the leave-one-out method revealed no substantial change in pooled effect estimates; (Risk Ratio) RR 47.2% to RR 49.8% demonstrating the robustness of our results. There was no evidence of publication bias as assessed from the funnel plot symmetry. Ketoconazole containing regimens have shown moderate efficacy in high risk CRPC patients as demonstrated by the pooled results. Hence, a ketoconazole based chemotherapy can be added to patients' regimen if there is a persistent rise in PSA levels after androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Ketoconazole; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists
PubMed: 38296679
DOI: 10.1016/j.clgc.2024.01.003 -
Clinical Genitourinary Cancer Apr 2024Poly (ADP-ribose) polymerase inhibitors (PARPi) represent an option in selected cases of metastatic castration-resistant prostate cancer (mCRPC). The aim of the present... (Meta-Analysis)
Meta-Analysis Review
Poly (ADP-ribose) polymerase inhibitors (PARPi) represent an option in selected cases of metastatic castration-resistant prostate cancer (mCRPC). The aim of the present systematic review and meta-analysis is to evaluate the efficacy and safety of approved (Olaparib, Rucaparib) and investigational (Talazoparib, Niraparib, Veliparib) PARPi in mCRPC patients. Three databases were queried for studies analyzing oncological outcomes and adverse events of mCRPC patients receiving PARPi. Primary outcome was a PSA decline ≥ 50% from baseline. Secondary outcomes were objective response rate, progression-free survival (PFS), radiological PFS, overall survival (OS), conversion of circulating tumor cell count, and time to PSA progression. The number and rate of any grade adverse events (AEs), grade ≥ 3 AEs, and most common grade ≥ 3 AEs were registered. A subanalysis of outcomes per mutation type, prospective trials, and studies adopting combination therapies was performed. Overall, 31 studies were included in this systematic review, 28 of which are available for meta-analysis. The most frequently investigated drug was Olaparib. The most frequent mutation was BRCA2. A PSA decline rate of 43% (95% CI 0.32-0.54) was observed in the overall population. Mean OS was 15.9 (95% CI 12.9-19.0) months. In BRCA2 patients, PSA decline rate was 66% (95% CI 0.57-0.7) and OS 23.4 months (95% CI 22.8-24.1). Half of the patients suffered from grade 3 and 4 AEs (0.50 [95% CI 0.39-0.60]). Most common AEs were hematological, the most frequent being anemia (21.5%). PARP inhibitors represent a viable option for mCRPC patients. Current evidence suggests an increased effectiveness in homologous recombination repair (HRR) gene mutation carriers, especially BRCA2.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Prospective Studies; Mutation
PubMed: 38281877
DOI: 10.1016/j.clgc.2023.12.011 -
International Journal of Molecular... Jan 2024Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the... (Meta-Analysis)
Meta-Analysis Review
Alzheimer's Disease (AD) is the most common neurodegenerative disease which manifests with progressive cognitive impairment, leading to dementia. Considering the noninvasive collection of saliva, we designed the systematic review to answer the question "Are salivary biomarkers reliable for the diagnosis of Alzheimer's Disease?" Following the inclusion and exclusion criteria, 30 studies were included in this systematic review (according to the PRISMA statement guidelines). Potential biomarkers include mainly proteins, metabolites and even miRNAs. Based on meta-analysis, in AD patients, salivary levels of beta-amyloid42 and p-tau levels were significantly increased, and t-tau and lactoferrin were decreased at borderline statistical significance. However, according to pooled AUC, lactoferrin and beta-amyloid42 showed a significant predictive value for salivary-based AD diagnosis. In conclusion, potential markers such as beta-amyloid42, tau and lactoferrin can be detected in the saliva of AD patients, which could reliably support the early diagnosis of this neurodegenerative disease.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Lactoferrin; MicroRNAs; Biomarkers
PubMed: 38256241
DOI: 10.3390/ijms25021168 -
International Journal of Molecular... Jan 2024Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical... (Meta-Analysis)
Meta-Analysis Review
Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical recurrence (BCR), and lymph node metastasis (LNM). The ability to predict LVI preoperatively in PCa may be useful for proposing variations in the diagnosis and management strategies. We performed a systematic review and meta-analysis to identify preoperative clinicopathological factors that correlate with LVI in final histopathological specimens in PCa patients. Systematic literature searches of PubMed, Embase, and Web of Science were performed up to 31 January 2023. A total of thirty-nine studies including 389,918 patients were included, most of which were retrospective and single-center. PSA level, clinical T stage, and biopsy Gleason score were significantly correlated with LVI in PCa specimens. Meta-analyses revealed that these factors were the strongest predictors of LVI in PCa patients. Prostate volume, BMI, and age were not significant predictors of LVI. A multitude of preoperative factors correlate with LVI in final histopathology. Meta-analyses confirmed correlation of LVI in final histopathology with higher preoperative PSA, clinical T stage, and biopsy Gleason score. This study implies advancements in risk stratification and enhanced clinical decision-making, and it underscores the importance of future research dedicated to validation and exploration of contemporary risk factors in PCa.
Topics: Male; Humans; Prostate-Specific Antigen; Retrospective Studies; Prostatic Neoplasms; Biopsy; Clinical Decision-Making
PubMed: 38255928
DOI: 10.3390/ijms25020856 -
American Journal of Cardiovascular... Jan 2024Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors (PCSK9i) have a beneficial effect on various domains of patients' lipid profiles and cardiovascular and mortality outcomes. Here, we aim to further investigate the efficacy and safety of PCSK9i in patients with ACS or who experienced recent episodes.
METHODS
We comprehensively searched PubMed, Scopus, Web of Science and Cochrane CENTRAL to identify all randomized controlled trials comparing PCSK9i versus placebo. Data were extracted and analysed using Stata/MP version 17.0.
RESULTS
Eleven studies (n = 24,732) were included in this meta-analysis. In terms of efficacy outcomes, compared with the control group, PCSK9i significantly decreased levels of LDL-C, TC, TG, Lp (a) and Apo-B, with the following values, respectively: Cohen's d of - 1.25, 95% confidence interval (CI - 1.64 to - 0.87); Cohen's d of - 1.32, 95% CI (- 1.83 to - 0.81); Cohen's d of - 0.26, 95% CI (- 0.37 to - 0.14); Cohen's d of - 0.70, 95% CI (- 1.15 to - 0.26); and Cohen's d of - 1.46, 95% CI (- 1.97 to - 0.94). The levels of HDL-C and Apo-A1 increased by: Cohen's d 0.27, 95% CI (0.16-0.39) and Cohen's d of 0.30, 95% CI (0.17-0.42), respectively. Regarding safety outcomes, PCSK9i was associated with lower odds of myocardial infarction (MI) and cerebrovascular events with the following values, respectively: OR = 0.87, 95% CI (0.78-0.97) and OR = 0.71, 95% CI (0.52-0.98).
CONCLUSIONS
PCSK9i was associated with better lipid profile and quality of life of patients and can be recommended as an optimal treatment strategy. Further trials should study combinations of PCSK9i with other lipid-lowering drugs.
Topics: Humans; Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, LDL; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38241002
DOI: 10.1007/s40256-023-00621-5 -
Molecular Autism Jan 2024Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract.
METHODS
We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279).
RESULTS
There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]).
LIMITATIONS
All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults.
CONCLUSIONS
There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.
Topics: Adolescent; Child; Humans; Autistic Disorder; Biomarkers; Gastrointestinal Tract; Inflammation; Lactoferrin; Leukocyte L1 Antigen Complex
PubMed: 38233886
DOI: 10.1186/s13229-023-00575-0 -
International Journal of Cardiology Mar 2024To explore the safety and assess the cardiovascular impact of early in-hospital administration of PCSK9 inhibitors in patients with acute coronary syndrome (ACS). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the safety and assess the cardiovascular impact of early in-hospital administration of PCSK9 inhibitors in patients with acute coronary syndrome (ACS).
METHODS
A systematic search of PubMed, Web of Science, and Embase databases was conducted for studies involving the use of PCSK9 inhibitors in ACS patients from inception to October 2023. Two independent researchers screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using STATA 16.0 software.
RESULTS
Nine studies, encompassing a total of 2896 ACS patients, were included in the analysis. When compared to statin monotherapy, early administration of PCSK9 inhibitors during hospitalization for ACS proved effective in reducing the incidence of major adverse cardiovascular events (MACEs). This encompassed a decrease in coronary revascularization [Relative Risk (RR) = 0.78, 95% CI (0.62, 0.98), P < 0.05], recurrent ACS [RR = 0.62, 95% CI (0.42, 0.94), P < 0.05], readmissions due to unstable angina [RR = 0.71, 95% CI (0.59, 0.85), P < 0.01], and strokes [RR = 0.31, 95% CI (0.09, 1.04), P = 0.058]. There was no significant difference in the incidence of death between the two groups.The use of PCSK9 inhibitors notably hastened the reduction of LDL-C, TG, and Non HDL-C levels in the short term. Additionally, it increased HDL-C levels and the number of individuals meeting LDL-C compliance criteria. Importantly, the risk of adverse drug events, such as ALT increase >3xULN, allergies, and musculoskeletal pain, did not significantly elevate with PCSK9 inhibitor use.
CONCLUSION
The early administration of PCSK9 inhibitors has been found to safely and effectively lower diverse lipid levels in patients with ACS. This reduction is associated with a noteworthy decrease in MACEs, encompassing revascularization, recurrent ACS, and hospital readmissions.
Topics: Humans; Acute Coronary Syndrome; PCSK9 Inhibitors; Proprotein Convertase 9; Cholesterol, LDL; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hospitals; Anticholesteremic Agents
PubMed: 38211676
DOI: 10.1016/j.ijcard.2024.131775 -
Practical Radiation Oncology 2024Our purpose was to develop a summary of recommendations regarding the management of patients with clinically localized prostate cancer based on the American Urologic...
PURPOSE
Our purpose was to develop a summary of recommendations regarding the management of patients with clinically localized prostate cancer based on the American Urologic Association/ ASTRO Guideline on Clinically Localized Prostate Cancer.
METHODS
The American Urologic Association and ASTRO convened a multidisciplinary, expert panel to develop recommendations based on a systematic literature review using an a priori defined consensus-building methodology. The topics covered were risk assessment, staging, risk-based management, principles of management including active surveillance, surgery, radiation, and follow-up after treatment. Presented are recommendations from the guideline most pertinent to radiation oncologists with an additional statement on health equity, diversity, and inclusion related to guideline panel composition and the topic of clinically localized prostate cancer.
SUMMARY
Staging, risk assessment, and management options in prostate cancer have advanced over the last decade and significantly affect shared decision-making for treatment management. Current advancements and controversies discussed to guide staging, risk assessment, and treatment recommendations include the use of advanced imaging and tumor genomic profiling. An essential active surveillance strategy includes prostate-specific antigen monitoring and periodic digital rectal examination with changes triggering magnetic resonance imaging and possible biopsy thereafter and histologic progression or greater tumor volume prompting consideration of definitive local treatment. The panel recommends against routine use of adjuvant radiation therapy (RT) for patients with prostate cancer after prostatectomy with negative nodes and an undetectable prostate-specific antigen, while acknowledging that patients at highest risk of recurrence were relatively poorly represented in the 3 largest randomized trials comparing adjuvant RT to early salvage and that a role may exist for adjuvant RT in selected patients at highest risk. RT for clinically localized prostate cancer has evolved rapidly, with new trial results, therapeutic combinations, and technological advances. The recommendation of moderately hypofractionated RT has not changed, and the updated guideline incorporates a conditional recommendation for the use of ultrahypofractionated treatment. Health disparities and inequities exist in the management of clinically localized prostate cancer across the continuum of care that can influence guideline concordance.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms; Biopsy; Consensus; Genomics
PubMed: 38182303
DOI: 10.1016/j.prro.2023.09.007 -
Clinical Neurology and Neurosurgery Jan 2024Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute ischemic stroke (AIS) is a leading cause of death and disability. AIS is caused by an embolus or thrombus that restricts blood flow to the brain tissue. Despite intravenous thrombolysis and endovascular thrombectomy, a substantial number of patients do not achieve effective reperfusion. Argatroban, a direct thrombin inhibitor, can potentially improve neurological outcomes in AIS patients. However, there are conflicting results in the medical literature regarding the efficacy and safety of argatroban in this context.
OBJECTIVE
This study aims to evaluate the efficacy and safety of argatroban as monotherapy or adjunct therapy for acute ischemic stroke.
METHODS
Five major databases (PubMed, Embase, Scopus, Web of Science, and Cochrane Library) were searched for randomized controlled trials (RCTs) that compared the efficacy and safety of using argatroban alone or in combination with recombinant tissue plasminogen activator (r-TPA) in the management protocol of the AIS. We used Review Manager Software (RevMan 5.4.1) for data analysis.
RESULTS
We included 1393 patients from eight RCTs (of them, 726 were treated with argatroban alone or combined with r-TPA, while 667 received the placebo, standard therapy (standard treatments based on current guidelines including antihypertensive, antiplatelet agents, and statins) or endovascular r-TPA). Neither argatroban vs control nor argatroban with r-TPA vs r-TPA showed significant difference regarding the activity in daily living; (SMD= 1.69, 95% CI [-0.23, 3.61]; p = 0.09), (SMD= 0.99, 95% CI [-0.88, 2.86]; p = 0.30), respectively. Also, there was no significant difference in the National Institutes of Health Stroke Scale (NIHSS) score at seven days, the number of patients achieving modified Rankin Scale (mRS) of 0-1 or 0-2 at 90 days (p > 0.05). Argatroban did not significantly increase the risk of adverse events or symptomatic intracranial hemorrhage (ICH), or major systemic bleeding compared to control or r-TPA (p > 0.05) CONCLUSIONS: Argatroban does not demonstrate superior efficacy compared to placebo or standard therapy in terms of ADL, NIHSS and mRS outcomes. Importantly, argatroban does not significantly increase the incidence of adverse events, including symptomatic ICH and systemic bleeding.
Topics: Humans; Arginine; Brain Ischemia; Fibrinolytic Agents; Intracranial Hemorrhages; Ischemic Stroke; Pipecolic Acids; Stroke; Sulfonamides; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 38176219
DOI: 10.1016/j.clineuro.2023.108097 -
International Wound Journal Apr 2024This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science,... (Meta-Analysis)
Meta-Analysis Review
This study aims to evaluate the clinical effects of different blood derivatives on wound healing using network meta-analysis. PubMed, Embase, OVID, Web of Science, SCOPUS and Cochrane Central were searched to obtain studies about blood derivatives on wound healing until October 2023. R 4.2.0 and Stata 15.0 softwares were used for data analysis. Forty-four studies comprising 5164 patients were included. The results of network meta-analysis showed that the healing area from high to low was GF + ORCCB, ORCCB, GF, PRF, Unnas paste dressing, APG, PRP injection, PRP, PRP + thrombin gel, PPP, HPL, CT. The healing time from low to high was PRP + thrombin gel, GF, PRP, PC + K, PC, APG, PRF, CT, Silver sulfadiazine ointment. The number of patients cured from high to low was APG, PRP injection, PRP, Aurix, PRF, Leucopatch, HPL, Antimicrobial Ointment Dressing, CT, 60 μg/cm repifermin, 120 μg/cm repifermin, AFG, PPP. The order of analgesic effect from high to low was AFG, Aminogam gel, PRF, PRP, Oxidised oil, APG, GF, CT. The order of the number of wound infection cases from low to high is APG, 20 μg/cm repifermin, 60 μg/cm repifermin, PRP, LeucoPatch, CT, PPP, Antiseptic ointment dressing. Healing area: GF + ORCCB had the best effect; Healing time: PRP + thrombin gel took the shortest time. The number of cured patients and the reduction of wound infection: APG has the best effect. Analgesic effect: AFG has the best effect. More studies with large sample sizes are needed to confirm the above findings.
Topics: Humans; Network Meta-Analysis; Thrombin; Ointments; Fibroblast Growth Factor 10; Wound Healing; Treatment Outcome; Wound Infection; Analgesics; Platelet-Rich Plasma
PubMed: 38158884
DOI: 10.1111/iwj.14622