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Critical Reviews in Oncology/hematology Jan 2024Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes.
PATIENT AND METHODS
We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered.
DATA EXTRACTION AND SYNTHESIS
A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals.
RESULTS
This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy.
CONCLUSIONS
Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI).
Topics: Humans; Female; Bevacizumab; Poly(ADP-ribose) Polymerase Inhibitors; Network Meta-Analysis; Bayes Theorem; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
PubMed: 38065404
DOI: 10.1016/j.critrevonc.2023.104229 -
Advances in Nutrition (Bethesda, Md.) Jan 2024Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Dairy intake may influence cognition through several molecular pathways. However, epidemiologic studies yield inconsistent results, and no dose-response meta-analysis has been conducted yet. Therefore, we performed a systematic review with a dose-response meta-analysis about the association between dairy intake and cognitive decline or incidence of dementia. We investigated prospective studies with a follow-up ≥6 mo on cognitive decline or dementia incidence in adults without known chronic conditions through a systematic search of Embase, Medline, Cochrane Library, Web of Science, and Google Scholar from inception to 11 July 2023. We evaluated the dose-response association using a random-effects model. We identified 15 eligible cohort studies with >300,000 participants and a median follow-up of 11.4 y. We observed a negative nonlinear association between cognitive decline/dementia incidence and dairy intake as assessed through the quantity of consumption, with the nadir at ∼150 g/d (risk ratio: 0.88; 95% confidence interval: 0.78, 0.99). Conversely, we found an almost linear negative association when we considered the frequency of consumption (risk ratio for linear trend: 0.84; 95% confidence interval: 0.77, 0.92 for 1 time/d increase of dairy products). Stratified analysis by dairy products showed different shapes of the association with linear inverse relationship for milk intake, whereas possibly nonlinear for cheese. The inverse association was limited to Asian populations characterized by generally lower intake of dairy products, compared with the null association reported by European studies. In conclusion, our study suggests a nonlinear inverse association between dairy intake and cognitive decline or dementia, also depending on dairy types and population characteristics, although the heterogeneity was still high in overall and several subgroup analyses. Additional studies should be performed on this topic, including a wider range of intake and types of dairy products, to confirm a potential preventing role of dairy intake on cognitive decline and identify ideal intake doses. This review was registered at PROSPERO as CRD42020192395.
Topics: Animals; Humans; Cognitive Dysfunction; Dairy Products; Dementia; Diet; Milk; Prospective Studies; Risk Factors
PubMed: 38043604
DOI: 10.1016/j.advnut.2023.100160 -
Radiology and Oncology Dec 2023The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The outcome of systemic therapy (ST) for unresectable and metastatic intrahepatic cholangiocarcinoma (iCCA) is poor. This study aims to further evaluate the efficacy and safety of locoregional therapy combined with systemic therapy (LRT + ST) compared with only ST in unresectable and metastatic iCCA by performing a systematic literature review and meta-analysis.
METHODS
A comprehensive search was performed in PubMed, Web of Science, EMBASE, and the Cochrane Library up to November 3, 2022. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).
RESULTS
Ten retrospective cohort studies with 3,791 unresectable or metastatic iCCA patients were enrolled in this study, including 1,120 who received ablation, arterially directed therapy (ADT), or external beam radiation therapy (EBRT) combined with ST. The meta-analysis showed that the LRT + ST group had a better OS ( = 0.51; =0.41-0.64; < 0.001), PFS ( = 0.40, = 0.22-0.71, = 0.002) and ORR ( = 1.68; = 1.17-2.42; = 0.005). Subgroup analysis showed that both ST combined with ADT ( = 0.42, = 0.31-0.56, < 0.001) and EBRT ( = 0.67, = 0.63-0.72, < 0.001) could improve OS. Neutropenia, thrombocytopenia, anemia, anorexia, and vomiting did not show significant differences between the groups (p value > 0.05).
CONCLUSIONS
Compared with only ST, LRT + ST improved survival outcomes for unresectable and metastatic iCCA patients without increasing severe AEs, which can further provide a basis for guidelines.
Topics: Humans; Retrospective Studies; Cholangiocarcinoma; Progression-Free Survival; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 38038416
DOI: 10.2478/raon-2023-0059 -
EJHaem Nov 2023Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients.... (Review)
Review
Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.
PubMed: 38024642
DOI: 10.1002/jha2.801 -
Frontiers in Nutrition 2023Central obesity may contribute to breast cancer (BC); however, there is no dose-response relationship. This meta-analysis examined the effects of central obesity on BC...
PURPOSE
Central obesity may contribute to breast cancer (BC); however, there is no dose-response relationship. This meta-analysis examined the effects of central obesity on BC and their potential dose-response relationship.
METHODS
In the present study, PubMed, Medline, Embase, and Web of Science were searched on 1 August 2022 for published articles. We included the prospective cohort and case-control studies that reported the relationship between central obesity and BC. Summary effect size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (95% CI) and were evaluated using random-effect models. The inconsistency index () was used to quantify the heterogeneity magnitude derived from the random-effects Mantel-Haenszel model.
RESULTS
This meta-analysis included 57 studies (26 case-control and 31 prospective cohort) as of August 2022. Case-control studies indicated that waist circumference (WC) (adjusted OR = 1.18; 95% CI: 1.00-1.38; = 0.051) and waist-to-hip ratio (WHR) (adjusted OR = 1.28; 95% CI: 1.07-1.53; = 0.008) were significantly positively related to BC. Subgroup analysis showed that central obesity measured by WC increased the premenopausal (adjusted OR = 1.15; 95% CI: 0.99-1.34; = 0.063) and postmenopausal (adjusted OR = 1.18; 95% CI: 1.03-1.36; = 0.018) BC risk and the same relationship appeared in WHR between premenopausal (adjusted OR = 1.38; 95% CI: 1.19-1.59; < 0.001) and postmenopausal (adjusted OR = 1.41; 95% CI: 1.22-1.64; < 0.001). The same relationship was observed in hormone receptor-positive (HR+) (adjusted OR = 1.26; 95% CI: 1.02-1.57; = 0.035, adjusted OR = 1.41; 95% CI: 1.00-1.98; = 0.051) and hormone receptor-negative (HR-) (adjusted OR = 1.44; 95% CI: 1.13-1.83; = 0.003, adjusted OR = 1.42; 95% CI: 0.95-2.13; = 0.087) BCs. Prospective cohort studies indicated that high WC (adjusted RR = 1.12; 95% CI: 1.08-1.16; < 0.001) and WHR (adjusted RR = 1.05; 95% CI: 1.018-1.09; = 0.017) may increase BC risk. Subgroup analysis demonstrated a significant correlation during premenopausal (adjusted RR = 1.08; 95% CI: 1.02-1.14; = 0.007) and postmenopausal (adjusted RR = 1.14; 95% CI: 1.10-1.19; < 0.001) between BC and central obesity measured by WC, and WHR was significantly positively related to BC both premenopausal (adjusted RR = 1.04; 95% CI: 0.98-1.11; = 0.169) and postmenopausal (adjusted RR = 1.04; 95% CI: 1.02-1.07; = 0.002). Regarding molecular subtype, central obesity was significantly associated with HR+ (adjusted OR = 1.13; 95% CI: 1.07-1.19; < 0.001, adjusted OR = 1.03; 95% CI: 0.98-1.07; = 0.244) and HR- BCs (adjusted OR =1.11; 95% CI: 0.99-1.24; = 0.086, adjusted OR =1.01; 95% CI: 0.91-1.13; = 0.808). Our dose-response analysis revealed a J-shaped trend in the relationship between central obesity and BC (measured by WC and WHR) in case-control studies and an inverted J-shaped trend between BMI (during premenopausal) and BC in the prospective cohort.
CONCLUSION
Central obesity is a risk factor for premenopausal and postmenopausal BC, and WC and WHR may predict it. Regarding the BC subtype, central obesity is proven to be a risk of ER+ and ER- BCs. The dose-response analysis revealed that when BMI (during premenopausal) exceeded 23.40 kg/m, the risk of BC began to decrease, and WC higher than 83.80 cm or WHR exceeded 0.78 could efficiently increase the BC risk.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022365788.
PubMed: 38024370
DOI: 10.3389/fnut.2023.1236393 -
Biomolecules Nov 2023Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been... (Review)
Review
Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research.
Topics: Humans; Extracellular Traps; Prognosis; Neutrophils; Multiple Trauma
PubMed: 38002307
DOI: 10.3390/biom13111625 -
CNS Drugs Dec 2023The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research...
BACKGROUND AND OBJECTIVES
The renewed interest in psychedelic research provides growing evidence of potentially unique effects on various aspects of reward processing systems. Using the Research Domain Criteria (RDoC) framework, as proposed by the National Institute of Mental Health, we aim to synthesize the existing literature concerning the impact of lysergic acid diethylamide (LSD) on the RDoC's Positive Valence Systems (PVS) domain, and to identify potential avenues for further research.
METHODS
Two LSD-related terms (lysergic acid diethylamide and LSD) and 13 PVS-related terms (reward, happiness, bliss, motivation, reinforcement learning, operant, conditioning, satisfaction, decision making, habit, valence, affect, mood) were used to search electronic databases such as PubMed, Scopus, PsychINFO, and Web of Science for relevant articles. A manual search of the reference list resulted in nine additional articles. After screening, articles and data were evaluated and included based on their relevance to the objective of investigating the effects of LSD on the PVS. Articles and data were excluded if they did not provide information about the PVS, were observational in nature, lacked comparators or reference groups, or were duplicates. A risk of bias assessment was performed using the National Toxicology Program's Office of Health Assessment and Translation (NTP OHAT) risk of bias (RoB) tool. Data from the included articles were collected and structured based on the RDoC bio-behavioral matrix, specifically focusing on the PVS domain and its three constituent constructs: reward responsiveness, reward learning, and reward valuation.
RESULTS
We reviewed 28 clinical studies with 477 participants. Lysergic acid diethylamide, assessed at self-report (23 studies), molecular (5 studies), circuit (4 studies), and paradigm (3 studies) levels, exhibited dose-dependent mood improvement (20 short-term and 3 long-term studies). The subjective and neural effects of LSD were linked to the 5-HT receptor (molecular). Animal studies (14 studies) suggested LSD could mildly reinforce conditioned place preference without aversion and reduce responsiveness to other rewards. Findings on reward learning were inconsistent but hinted at potential associative learning enhancements. Reward valuation measures indicated potential reductions in effort expenditure for other reinforcers.
CONCLUSION
Our findings are consistent with our previous work, which indicated classical psychedelics, primarily serotonin 2A receptor agonists, enhanced reward responsiveness in healthy individuals and patient populations. Lysergic acid diethylamide exhibits a unique profile in the reward learning and valuation constructs. Using the RDoC-based framework, we identified areas for future research, enhancing our understanding of the impact of LSD on reward processing. However, applying RDoC to psychedelic research faces limitations due to diverse study designs that were not initially RDoC-oriented. Limitations include subjective outcome measure selection aligned with RDoC constructs and potential bias in synthesizing varied studies. Additionally, some human studies were open-label, introducing potential bias compared to randomized, blinded studies.
Topics: Animals; Humans; Hallucinogens; Lysergic Acid Diethylamide; Serotonin Receptor Agonists; Affect; Self Report
PubMed: 37999867
DOI: 10.1007/s40263-023-01044-1 -
Current Allergy and Asthma Reports Dec 2023The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these... (Review)
Review
PURPOSE OF REVIEW
The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these patients towards personalized and precision medicine. Surgery has been positioned as a suitable alternative in patients who do not achieve control with appropriate medical treatment, but polypoid recurrences remain a constraint. The emergence of new surgical approaches based on patient phenotyping and the poor disease control associated with type 2 inflammatory phenotype makes it necessary to review the role of personalized and precision surgery in managing the disease.
RECENT FINDINGS
Surgical approaches based on wide resection of bony sinus structures and the treatment of mucosa lining the sinonasal cavity have been analyzed and compared with other techniques and seem to offer more favorable surgical outcomes and improved quality of life (QoL), in addition to lower relapse rates. The innovations with new complementary surgical techniques, such as reboot surgery adding an extended autologous mucosal graft from the nasal floor (mucoplasty), may benefit endoscopic and QoL outcomes in the most severe CRSwNP patients with type 2 phenotype. Using bilateral endonasal mucoplasty as a complementary technique to reboot surgery is a suitable technical choice that has improved short- and medium-term QoL and endoscopic outcomes for patients with severe CRSwNP. These results are likely due to a combination of the extension of reboot and the inherent inflammatory and healing properties of mucoplasty. We propose this technique as a valuable surgical resource, although more robust clinical studies are needed to evaluate its long-term benefits comprehensively.
Topics: Humans; Rhinitis; Quality of Life; Nasal Polyps; Rhinosinusitis; Sinusitis; Chronic Disease
PubMed: 37991673
DOI: 10.1007/s11882-023-01113-x -
BMC Pharmacology & Toxicology Nov 2023Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density... (Meta-Analysis)
Meta-Analysis
PURPOSE
Dyslipidemia, characterized by elevated levels of triglycerides (TG), low-density lipoprotein (LDL), total cholesterol (TC), and reduced levels of high-density lipoprotein (HDL), is a major risk factor for cardiovascular diseases (CVD). Several studies have shown the potential of acarbose in improving serum lipid markers. However, there have been conflicting results on the topic in adults. Therefore, a comprehensive systematic review and meta-analysis was conducted to assess the impact of acarbose on lipid profiles.
METHODS
The random-effects approach was used to combine the data, and the results were provided as weighted mean difference (WMD) with 95% confidence intervals (CI).
RESULTS
Our meta-analysis included a total of 74 studies with a combined sample size of 7046 participants. The results of the analysis showed that acarbose resulted in a reduction in levels of TG (WMD = - 13.43 mg/dl, 95% CI: - 19.20, - 7.67; P < 0.001) and TC (WMD = - 1.93 mg/dl, 95% CI: - 3.71, - 0.15; P = 0.033), but did not affect other lipid markers. When conducting a nonlinear dose-response analysis, we found that acarbose was associated with an increase in levels of HDL (coefficients = 0.50, P = 0.012), with the highest increase observed at a dosage of 400 mg/d. Furthermore, our findings suggested a non-linear relationship between the duration of the intervention and TC (coefficients = - 18.00, P = 0.032), with a decline observed after 50 weeks of treatment.
CONCLUSION
The findings of this study suggest that acarbose can reduce serum levels of TG and TC. However, no significant effects were observed on LDL or HDL levels.
Topics: Adult; Humans; Lipids; Acarbose; Randomized Controlled Trials as Topic; Triglycerides; Dyslipidemias; Biomarkers; Lipoproteins, HDL
PubMed: 37990256
DOI: 10.1186/s40360-023-00706-6 -
Mutation Research. Reviews in Mutation... 2024Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are... (Comparative Study)
Comparative Study Review
Head and neck cancer is the seventh most common malignancy globally. Head and neck squamous cell carcinoma (HNSCC) originates from squamous cells and 90% of HNC are HNSCC. The gold standard for diagnosing HNSCC is tissue biopsy. However, given tumour heterogeneity, biopsies may miss important cancer-associated molecular signatures, and more importantly, after the tumour is excised, there is no means of tracking response to treatment in patients. Captured under liquid biopsy, circulating tumour DNA (ctDNA), may identify in vivo molecular genotypes and complements tumour tissue analysis in cancer management. A systematic search was conducted in PubMed, Embase, Scopus and the Cochran Library between 2012 to early 2023 on ctDNA in HNSCC using publications written in English. We summarise 20 studies that compared mutational profiles between tumour tissue DNA (tDNA) and ctDNA, using a cohort of 631 HNSCC patients and 139 controls. Among these studies, the concordance rates varied greatly and the most mutated and the most concordant gene was TP53, followed by PIK3CA, CDKN2A, NOTCH1 and FAT1. Concordant variants were mainly found in Stage IV tumours, and the mutation type is mostly single nucleotide variants (SNV). We conclude that, as a biomarker for HNSCC, ctDNA demonstrates great promise as it recapitulates tumour genotypes, however additional multi-central trials are needed.
Topics: Humans; Circulating Tumor DNA; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mutation; Class I Phosphatidylinositol 3-Kinases; Biomarkers, Tumor; Tumor Suppressor Protein p53; Receptor, Notch1; DNA, Neoplasm; Cyclin-Dependent Kinase Inhibitor p16; Cadherins
PubMed: 37977279
DOI: 10.1016/j.mrrev.2023.108477