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Translational Cancer Research May 2024Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic...
Efficacy and safety of anlotinib in combination with immune checkpoint inhibitors or not as advanced non-small cell lung cancer treatment: a systematic review and network meta-analysis.
BACKGROUND
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Combined anlotinib and immune checkpoint inhibitors (ICIs) therapy may have synergistic antitumor effects in NSCLC. This study aimed to comparing the efficacy and safety of anlotinib and ICIs treatment, monotherapy and combination in NSCLC.
METHODS
We performed a systematic review and network meta-analysis of 14 studies involving 4,308 NSCLC patients across four regimens: anlotinib, ICIs, anlotinib plus ICIs, and placebo. Efficacy outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Safety outcomes included treatment-related adverse events (TRAEs), TRAE grade three or higher (TRAE ≥3). Analyses were performed in RevMan 5.3 and R 3.5.1 (gemtc package). P<0.05 or effect estimate with 95% confidence interval (CI) that did not include 1 indicated statistical significance.
RESULTS
Fourteen publications involving 4,308 patients across four treatment regimens (anlotinib, ICIs, anlotinib plus ICIs, placebo) were included. For PFS, network meta-analysis showed all three interventions significantly improved PFS versus placebo. Anlotinib plus ICIs demonstrated the greatest PFS improvement [hazard ratio (HR) =0.24; 95% CI: 0.14, 0.36], followed by anlotinib (HR =0.37; 95% CI: 0.23, 0.58), and ICIs (HR =0.43; 95% CI: 0.27, 0.67). For OS, compared to placebo, anlotinib plus ICIs showed the greatest OS improvement (HR =0.52; 95% CI: 0.33, 0.74), followed by anlotinib (HR =0.66; 95% CI: 0.47, 0.95), and ICIs (HR =0.72; 95% CI: 0.54, 0.97). For ORR, anlotinib plus ICIs demonstrated the greatest improvement versus placebo [odds ratio (OR) =5.29; 95% CI: 3.32, 8.58], followed by anlotinib (OR =4.38; 95% CI: 2.42, 8.19), and ICIs (OR =2.17; 95% CI: 1.65, 2.89). For DCR, anlotinib plus ICIs showed the greatest improvement versus placebo (OR =13.32; 95% CI: 4.99, 45.09), followed by anlotinib (OR =5.56; 95% CI: 2.17, 14.38), and ICIs (OR =3.46; 95% CI: 1.29, 10.85). Compared to placebo, anlotinib was associated with the highest risk of TRAEs (OR =3.67, 95% CI: 1.12, 15.77), followed by ICIs (OR =1.83; 95% CI: 1.26, 2.69). Due to lack of data on anlotinib plus ICIs, no comparison was conducted. For grade ≥3 TRAEs, compared to placebo, anlotinib increased the risk (OR =3.67; 95% CI: 1.12, 15.77), while anlotinib plus ICIs (OR =2.45; 95% CI: 0.51, 11.6) and ICIs (OR =1.29; 95% CI: 0.33, 4.38) did not increase the risk.
CONCLUSIONS
Anlotinib combined with ICIs demonstrates improved efficacy over monotherapy for NSCLC treatment, without increased adverse events.
PubMed: 38881944
DOI: 10.21037/tcr-23-1483 -
Endocrinology, Diabetes & Metabolism Jul 2024Diabetes mellitus (DM) is a chronic metabolic disorder characterised by high blood sugar (BS) levels due to impaired insulin production or insulin resistance. It is a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Diabetes mellitus (DM) is a chronic metabolic disorder characterised by high blood sugar (BS) levels due to impaired insulin production or insulin resistance. It is a global health concern with significant implications for morbidity and mortality. Persian medicine has long utilised natural remedies, such as Pistacia atlantica Desf., for various diseases. In this randomised clinical trial, the effects of P. atlantica oleoresin in the improvement of lipid profiles, glucose indices and blood pressure (BP) were assessed in patients with Type 2 DM.
MATERIALS AND METHODS
In this randomised, single-blind, placebo-controlled study, 42 patients with Type 2 DM were randomly allocated to receive either P. atlantica oleoresin or placebo capsule for 3 months. Patients were evaluated prior to and 12 weeks after the beginning of the intervention, in terms of changes in lipid profiles, glucose indices and BP.
RESULTS
After 3 months, the mean BP in patients with DM receiving P. atlantica oleoresin was significantly reduced compared with the baseline (p = 0.001). Also, these changes were significantly higher than those of the control group. The mean of total cholesterol (p = 0.89), low-density lipoprotein (LDL) (p = 0.43) and triglyceride (TG) (p = 0.98) in the intervention group after 3 months was lower than that in the control group, but this difference was not statistically significant.
CONCLUSION
After 3 months, there was no significant difference between the P. atlantica and control groups in terms of blood sugar and lipid profiles. The mean BP in patients with DM receiving P. atlantica oleoresin was significantly reduced compared with that in the beginning of the study. Also, these changes were significant compared with the control group.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Single-Blind Method; Middle Aged; Female; Plant Extracts; Blood Glucose; Pistacia; Blood Pressure; Adult; Lipids; Phytotherapy; Aged
PubMed: 38881209
DOI: 10.1002/edm2.504 -
American Journal of Ophthalmology Jun 2024To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children.
PURPOSE
To study the long-term effects of perinatal high-dose recombinant human erythropoietin (rhEPO) on macular structural and vascular development in preterm children.
DESIGN
Randomized, double-blind clinical trial follow-up plus cohort study.
METHODS
Setting: Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland.
STUDY POPULATION
extremely or very preterm born children aged 7-15 years from an ongoing neuropediatric study (EpoKids). These had been previously randomized to receive either high-dose rhEPO or placebo perinatally.
INCLUSION CRITERIA
participation in the EpoKids Study, written informed consent (IC).
EXCLUSION CRITERIA
previous ocular trauma or surgery; retinal or developmental disease unrelated to prematurity. Term-born children of comparable age were enrolled as a healthy control (HC) group.
INCLUSION CRITERIA
term birth, IC.
EXCLUSION CRITERIA
any ocular or visual abnormality, high refractive error. Examiners were blinded regarding intervention status until completion of all analyses. (Participants/guardians remain blinded).
OBSERVATION PROCEDURES
Spectral-domain OCT scans (Heidelberg Spectralis system) and OCTA imaging (Zeiss PlexElite 9000) were obtained. Ophthalmological and orthoptic examinations excluded ocular comorbidities.
MAIN OUTCOME MEASURES
OCT (central retinal thickness, CRT; total macular volume, TMV), superficial plexus OCTA (foveal avascular zone, FAZ; vessel density, VD; vessel length density, VLD) parameters and foveal hypoplasia grade according to published criteria.
RESULTS
Macular vessel density parameters (VD and VLD) were significantly lower (p =0.015, CI-95: 0.01 to 0.06 and p=0.015, CI-95: 0.74 to 3.64) in the EPO group (n= 52) when compared to placebo (n=35). No other significant differences were observed between the EPO and placebo group. When comparing the intervention subgroups to HC we found six significant differences in OCT and OCTA parameters (FAZ, VD, VLD and CRT comparing HC and EPO group; FAZ and CRT when comparing HC and placebo group).
CONCLUSIONS
Early high-dose rhEPO in infants born extremely or very preterm affects macular vessel density parameters compared to placebo. Premature birth (regardless of intervention status) affects retinal structure and vascular development. Our findings on macular vascular development do not contraindicate the administration of early high-dose EPO in preterm infants. For further understanding of the role of EPO on macular development and its clinical significance, future studies are needed.
PubMed: 38880371
DOI: 10.1016/j.ajo.2024.06.005 -
Scientific Reports Jun 2024Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of...
Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p < 0.001). Despite alterations in mitochondrial content and morphology in the myocardium, as assessed per transmission electron microscopy, mitochondrial function was unchanged. DMF treatment counteracted 25% of the proteomic changes induced by CA in the brain, and preserved mitochondrial structure in the myocardium. DMF demonstrates a potential therapeutic benefit in preserving mitochondrial integrity following asphyxia-induced IHCA. Further investigation is warranted to fully elucidate DMF's protective mechanisms and optimize its therapeutic application in post-arrest care.
Topics: Animals; Heart Arrest; Asphyxia; Swine; Disease Models, Animal; Dimethyl Fumarate; Mitochondria; Brain; Humans; Myocardium; Oxidative Phosphorylation
PubMed: 38879681
DOI: 10.1038/s41598-024-64317-9 -
The American Journal of Clinical... Jun 2024A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated...
Fatty acid desaturase insertion-deletion polymorphism rs66698963 predicts colorectal polyp prevention by the n-3 fatty acid eicosapentaenoic acid: A secondary analysis of the seAFOod polyp prevention trial.
BACKGROUND
A fatty acid desaturase (FADS) insertion-deletion (Indel) polymorphism (rs66698963) influences expression of FADS1, which controls synthesis of n-6 highly unsaturated fatty acid (HUFA) arachidonic acid (AA). The anti-inflammatory activity of the n-3 HUFA eicosapentaenoic acid (EPA) may be explained by competition with AA for pro-inflammatory lipid mediator synthesis. A precision medicine approach based on stratification by FADS Indel genotype could identify individuals, who benefit from greatest disease risk reduction by n-3 HUFAs.
OBJECTIVE
We tested the hypothesis that the FADS insertion (I) allele predicts colorectal polyp risk reduction in a secondary analysis of the randomized, placebo-controlled, 2 x 2 factorial seAFOod polyp prevention trial of EPA 2000 mg daily and aspirin 300 mg daily for 12 months (ISRCTN05926847).
METHODS
Participant Indel genotype was determined by PCR blind to trial outcomes. Colorectal polyp outcomes were included in negative binomial (polyp number) and logistic (polyp detection rate [PDR; percentage with one or more polyps]) regression models comparing each active intervention versus placebo. Presence of at least one Indel I allele and an interaction term (I allele x active intervention) were co-variates.
RESULTS
In 528 participants with colonoscopy and FADS Indel data, EPA use irrespective of Indel genotype, was not associated with reduced colorectal polyp number (incidence rate ratio [IRR] 0.92, 95% confidence interval 0.74, 1.16), mirroring original seAFOod trial analysis. However, presence of at least one I allele identified EPA users with a significant reduction in colorectal polyp number (IRR 0.50 [0.28, 0.90]), unlike aspirin, for which there was no interaction. Similar findings were obtained for the PDR.
CONCLUSIONS
The FADS Indel I allele identified individuals, who displayed colorectal polyp prevention by EPA with a similar effect size to aspirin. Assessment of rs66698963 as a biomarker of therapeutic response to n-3 HUFAs in other populations and healthcare settings is warranted.
TRIAL REGISTRATION
The seAFOod polyp prevention trial and STOP-ADENOMA study are registered with https://www.isrctn.com as ISRCTN05926847.
PubMed: 38879016
DOI: 10.1016/j.ajcnut.2024.06.004 -
Complementary Therapies in Medicine Jun 2024Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder...
INTRODUCTION
Obesity is associated with many chronic non-communicable diseases, including hypertension, diabetes, cardiovascular and cerebrovascular diseases, cancer, gallbladder disease, bone and joint disorders, skin diseases, fatty liver disease, etc. (Wharton et al., 2020) The recent report revealed that overweight and obesity were prevalent in 60 % of the adult population. Several studies have been published to determine the effect of Hibiscus sabdariffa Linn. on obesity treatment, but the findings are still inconclusive. The purpose of this study was to determine the efficacy and safety of H. sabdariffa Linn in the treatment of obesity.
METHODS
We searched PubMed, EMBASE, and CENTRAL from inception to February 2024. Randomized controlled trials (RCTs) were included if they explored the effect of H. sabdariffa on one of the following outcomes: body weight, body mass index (BMI), waist circumference, and waist-to-hip ratio. A random-effects model was used to meta-analyze the data. I was used to quantify statistical heterogeneity among the included RCTs. PROSPERO registered protocol: CRD42023408880.
RESULTS
A total of six RCTs with 339 participants were included. Four trials used H. sabdariffa extract in capsules as the intervention of interest compared to placebo, while the other two trials used H. sabdariffa tea compared to black or green tea. Our meta-analyses showed that the mean difference in weight reduction between H. sabdariffa and control was - 0.27 kg (95 % confidence interval (CI); - 1.98 to 1.42, I = 0.0 %). The mean differences for BMI and waist circumference reduction were - 0.06 kg/m (95 % CI; - 0.58 to 0.47, I = 0.0 %) and - 0.20 centimeters (95 % CI; - 2.06 to 1.66, I = 0.00 %). No safety concerns were reported in the included studies.
CONCLUSION
Our study did not show a clinical benefit of H. sabdariffa extract in obesity treatment. However, further high-quality RCTs with a longer treatment duration and a standard dose are still warranted.
PubMed: 38878905
DOI: 10.1016/j.ctim.2024.103063 -
Diabetology & Metabolic Syndrome Jun 2024Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is...
BACKGROUND
Prediabetes is a condition preceding the development of diabetes and is associated with an increased risk of a number of complications. The primary mode of management is thought to be lifestyle modification. Pharmacological therapy, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs), were not well addressed in the literature and were only evaluated in trials as secondary and exploratory outcomes with a limited sample size. Here, GLP-1RAs are evaluated as a comprehensive therapy approach for patients with prediabetes.
METHODS
A comprehensive search of Web of Science, SCOPUS, PubMed, and Cochrane was performed on May 5, 2023, to retrieve randomized controlled trials (RCTs) comparing the effect of GLP-1RAs to placebo and/or lifestyle modification on prediabetes reversion to normoglycemia, prevention of overt diabetes, glycemic control, anthropometric parameters, and lipid profiles. Review Manager (RevMan) version 5.4 was used. The quality of RCTs was assessed using the revised version of the Cochrane Risk of Bias Tool. GRADE was performed to evaluate the certainty of evidence.
RESULTS
Twelve trials involving 2903 patients in the GLP-1RAs group and 1413 in the control group were included in the meta-analysis. Low quality of evidence revealed that GLP-1RAs significantly increased the incidence of prediabetes reversion to the normoglycemic state [RR = 1.76, 95% CI (1.45, 2.13), P < 0.00001] and moderate quality of evidence showed that GLP-1RAs significantly prevented new-onset diabetes [RR = 0.28, 95% CI (0.19, 0.43), P < 0.00001]. Significant reductions in HbA1c, fasting plasma glucose, body weight, waist circumference, triglycerides, and LDL were observed in the GLP-1RAs arm (P < 0.05). However, higher incidences of gastrointestinal disorders were reported in the GLP-1RAs group (P < 0.05).
CONCLUSIONS
GLP-1RAs combined with lifestyle modification proved to be a more effective therapy for managing prediabetic patients than lifestyle modification alone, with a tolerable safety profile. Future guidelines should consider GLP-1RAs as an adjunct to lifestyle modification in the management of prediabetic patients to provide better management and improve treatment adherence.
PubMed: 38877565
DOI: 10.1186/s13098-024-01371-3 -
European Journal of Internal Medicine Jun 2024Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The...
BACKGROUND
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects.
METHODS
This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance.
RESULTS
There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's.
CONCLUSIONS
In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
PubMed: 38876929
DOI: 10.1016/j.ejim.2024.06.001 -
Complementary Therapies in Medicine Jun 2024The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials... (Review)
Review
OBJECTIVE
The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels.
METHODS
A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity.
RESULTS
In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001).
CONCLUSIONS
The findings of the present study showed that leptin levels might decline following GC administration.
REGISTRATION NUMBER
CRD42023486370.
PubMed: 38876392
DOI: 10.1016/j.ctim.2024.103060