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Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Journal of Advanced Research Dec 2023Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory... (Review)
Review
BACKGROUND
Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory reaction, myoglobinuria, hyperkalemia and acute kidney injury (AKI). Especially AKI, it is the leading cause of death from CS. There are various cell death forms in AKI, among which ferroptosis is a typical form of cell death. However, the role of ferroptosis has not been fully revealed in CS-AKI.
AIM OF REVIEW
This review aimed to summarize the evidence of ferroptosis in CS-AKI and its related molecular mechanism, discuss the therapeutic significance of ferroptosis in CS-AKI, and open up new ideas for the treatment of CS-AKI.
KEY SCIENTIFIC CONCEPTS OF REVIEW
One of the main pathological manifestations of CS-AKI is renal tubular epithelial cell dysfunction and cell death, which has been attributed to massive deposition of myoglobin. Large amounts of myoglobin released from damaged muscle deposited in the renal tubules, impeding the normal renal tubules function and directly damaging the tubules with oxidative stress and elevated iron levels. Lipid peroxidation damage and iron overload are the distinguishing features of ferroptosis. Moreover, high levels of pro-inflammatory cytokines and damage-associated molecule pattern molecules (HMGB1, double-strand DNA, and macrophage extracellular trap) in renal tissue have been shown to promote ferroptosis. However, how ferroptosis occurs in CS-AKI and whether it can be a therapeutic target remains unclear. In our current work, we systematically reviewed the occurrence and underlying mechanism of ferroptosis in CS-AKI.
Topics: Humans; Acute Kidney Injury; Cell Death; Crush Syndrome; Ferroptosis; Myoglobin
PubMed: 36702249
DOI: 10.1016/j.jare.2023.01.016 -
Advanced Biology Aug 2023Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss.... (Review)
Review
Obesity often results in severe negative health consequences and represents a growing issue for global health. Reducing food intake is a crucial factor for weight loss. Intermittent fasting is a relatively new intervention that contributes to weight reduction. Considering the intimate relationship between obesity and inflammatory pathologies with gut microbiota alterations, a systematic review of the literature was herein conducted to elucidate the relationship between time-restricted food intake and gut microbiota diversity in humans. Searches are carried out in three databases (PubMed, MedLine/OVID, and Academic Search Complete) between April 2019 and April 2022. Nine studies (all with longitudinal design) were identified as eligible by presenting data about the impact of intermittent fasting schemes on gut microbiota. At the phylum level, Firmicutes and Bacteroidetes increase throughout follow-ups, while 16 bacteria genera change their abundance in response to intermittent fasting. Finally, some genera associated with clinical predictors such as weight change, abdominal circumference, and metabolic variables were reported. Changes induced by fasting schemes positively impact the diversity and abundance of gut microbiota and the biomarkers described here. However, the changes previously reported have been studied in short periods and some return to their basal state after fasting intervention.
Topics: Humans; Animals; Obesity; Gastrointestinal Microbiome; Intermittent Fasting; Inflammation; Bacteria
PubMed: 36950759
DOI: 10.1002/adbi.202200337 -
JAMA Psychiatry Dec 2023Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Every third to sixth patient with medical diseases receives antidepressants, but regulatory trials typically exclude comorbid medical diseases. Meta-analyses of antidepressants have shown small to medium effect sizes, but generalizability to clinical settings is unclear, where medical comorbidity is highly prevalent.
OBJECTIVE
To perform an umbrella systematic review of the meta-analytic evidence and meta-analysis of the efficacy and safety of antidepressant use in populations with medical diseases and comorbid depression.
DATA SOURCES
PubMed and EMBASE were searched from inception until March 31, 2023, for systematic reviews with or without meta-analyses of randomized clinical trials (RCTs) examining the efficacy and safety of antidepressants for treatment or prevention of comorbid depression in any medical disease.
STUDY SELECTION
Meta-analyses of placebo- or active-controlled RCTs studying antidepressants for depression in individuals with medical diseases.
DATA EXTRACTION AND SYNTHESIS
Data extraction and quality assessment using A Measurement Tool for the Assessment of Multiple Systematic Reviews (AMSTAR-2 and AMSTAR-Content) were performed by pairs of independent reviewers following PRISMA guidelines. When several meta-analyses studied the same medical disease, the largest meta-analysis was included. Random-effects meta-analyses pooled data on the primary outcome (efficacy), key secondary outcomes (acceptability and tolerability), and additional secondary outcomes (response and remission).
MAIN OUTCOMES AND MEASURES
Antidepressant efficacy presented as standardized mean differences (SMDs) and tolerability (discontinuation for adverse effects) and acceptability (all-cause discontinuation) presented as risk ratios (RRs).
RESULTS
Of 6587 references, 176 systematic reviews were identified in 43 medical diseases. Altogether, 52 meta-analyses in 27 medical diseases were included in the evidence synthesis (mean [SD] AMSTAR-2 quality score, 9.3 [3.1], with a maximum possible of 16; mean [SD] AMSTAR-Content score, 2.4 [1.9], with a maximum possible of 9). Across medical diseases (23 meta-analyses), antidepressants improved depression vs placebo (SMD, 0.42 [95% CI, 0.30-0.54]; I2 = 76.5%), with the largest SMDs for myocardial infarction (SMD, 1.38 [95% CI, 0.82-1.93]), functional chest pain (SMD, 0.87 [95% CI, 0.08-1.67]), and coronary artery disease (SMD, 0.83 [95% CI, 0.32-1.33]) and the smallest for low back pain (SMD, 0.06 [95% CI, 0.17-0.39]) and traumatic brain injury (SMD, 0.08 [95% CI, -0.28 to 0.45]). Antidepressants showed worse acceptability (24 meta-analyses; RR, 1.17 [95% CI, 1.02-1.32]) and tolerability (18 meta-analyses; RR, 1.39 [95% CI, 1.13-1.64]) compared with placebo. Antidepressants led to higher rates of response (8 meta-analyses; RR, 1.54 [95% CI, 1.14-1.94]) and remission (6 meta-analyses; RR, 1.43 [95% CI, 1.25-1.61]) than placebo. Antidepressants more likely prevented depression than placebo (7 meta-analyses; RR, 0.43 [95% CI, 0.33-0.53]).
CONCLUSIONS AND RELEVANCE
The results of this umbrella systematic review of meta-analyses found that antidepressants are effective and safe in treating and preventing depression in patients with comorbid medical disease. However, few large, high-quality RCTs exist in most medical diseases.
Topics: Humans; Antidepressive Agents; Comorbidity; Depression; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 37672261
DOI: 10.1001/jamapsychiatry.2023.2983 -
JAMA Oncology May 2024To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%.
OBJECTIVE
To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials.
DATA SOURCES
MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients.
STUDY SELECTION
Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded.
MAIN OUTCOMES AND MEASURES
Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis.
RESULTS
Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%).
CONCLUSION AND RELEVANCE
This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.
Topics: Aged; Humans; Middle Aged; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Neoadjuvant Therapy; Treatment Outcome
PubMed: 38512301
DOI: 10.1001/jamaoncol.2024.0057 -
JAMA Network Open Jan 2024The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The NAPOLI 3 trial showed the superiority of fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin (NALIRIFOX) over the combination of gemcitabine and nab-paclitaxel (GEM-NABP) as first-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). Analyses comparing NALIRIFOX and GEM-NABP with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) have not yet been reported.
OBJECTIVE
To derive survival, response, and toxic effects data from phase 3 clinical trials and compare NALIRIFOX, FOLFIRINOX, and GEM-NABP.
DATA SOURCES
After a systematic search of PubMed, Scopus, Embase, and American Society of Clinical Oncology and European Society for Medical Oncology meetings' libraries, Kaplan-Meier curves were extracted from phase 3 clinical trials conducted from January 1, 2011, until September 12, 2023.
STUDY SELECTION
Phase 3 clinical trials that tested NALIRIFOX, FOLFIRINOX, or GEM-NABP as first-line treatment of metastatic PDAC and reported overall survival (OS) and progression-free survival (PFS) curves were selected. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data reporting guidelines.
DATA EXTRACTION AND SYNTHESIS
Individual patient OS and PFS data were extracted from Kaplan-Meier plots of original trials via a graphic reconstructive algorithm. Overall response rates (ORRs) and grade 3 or higher toxic effects rates were also collected. A pooled analysis was conducted, and results were validated via a network meta-analysis.
MAIN OUTCOMES AND MEASURES
The primary end point was OS. Secondary outcomes included PFS, ORR, and toxic effects rates.
RESULTS
A total of 7 trials with data on 2581 patients were analyzed, including 383 patients treated with NALIRIFOX, 433 patients treated with FOLFIRINOX, and 1756 patients treated with GEM-NABP. Median PFS was longer in patients treated with NALIRIFOX (7.4 [95% CI, 6.1-7.7] months) or FOLFIRINOX (7.3 [95% CI, 6.5-7.9] months; [HR], 1.21 [95% CI, 0.86-1.70]; P = .28) compared with patients treated with GEM-NABP (5.7 [95% CI, 5.6-6.1] months; HR vs NALIRIFOX, 1.45 [95% CI, 1.22-1.73]; P < .001). Similarly, GEM-NABP was associated with poorer OS (10.4 [95% CI, 9.8-10.8]; months) compared with NALIRIFOX (HR, 1.18 [95% CI, 1.00-1.39]; P = .05], while no difference was observed between FOLFIRINOX (11.7 [95% CI, 10.4-13.0] months) and NALIRIFOX (11.1 [95% CI, 10.1-12.3] months; HR, 1.06 [95% CI, 0.81-1.39]; P = .65). There were no statistically significant differences in ORR among NALIRIFOX (41.8%), FOLFIRINOX (31.6%), and GEM-NABP (35.0%). NALIRIFOX was associated with lower incidence of grade 3 or higher hematological toxic effects (eg, platelet count decreased 1.6% vs 11.8% with FOLFIRINOX and 10.8% with GEM-NABP), but higher rates of severe diarrhea compared with GEM-NABP (20.3% vs 15.7%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, NALIRIFOX and FOLFIRINOX were associated with similar PFS and OS as first-line treatment of advanced PDAC, although NALIRIFOX was associated with a different toxicity profile. Careful patient selection, financial toxic effects consideration, and direct comparison between FOLFIRINOX and NALIRIFOX are warranted.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Oxaliplatin; Gemcitabine; Fluorouracil; Adenocarcinoma
PubMed: 38190183
DOI: 10.1001/jamanetworkopen.2023.50756 -
Clinical and Experimental Rheumatology Oct 2023The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the... (Review)
Review
The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.
Topics: Humans; Animals; Mice; Behcet Syndrome; Dysbiosis; Epigenesis, Genetic; Uveitis; Microbiota; Bacteria
PubMed: 37382445
DOI: 10.55563/clinexprheumatol/zbt4gx -
Journal of Investigative Medicine : the... Aug 2023The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which... (Review)
Review
The therapeutic response heterogeneity in acromegaly persists, despite the medical-surgical advances of recent years. Thus, personalized medicine implementation, which focuses on each patient, is justified. Metabolomics would decipher the molecular mechanisms underlying the therapeutic response heterogeneity. Identification of altered metabolic pathways would open new horizons in the therapeutic management of acromegaly. This research aimed to evaluate the metabolomic profile in acromegaly and metabolomics' contributions to understanding disease pathogenesis. A systematic review was carried out by querying four electronic databases and evaluating patients with acromegaly through metabolomic techniques. In all, 21 studies containing 362 patients were eligible. Choline, the ubiquitous metabolite identified in growth hormone (GH)-secreting pituitary adenomas (Pas) by in vivo magnetic resonance spectroscopy (MRS), negatively correlated with somatostatin receptors type 2 expression and positively correlated with magnetic resonance imaging T2 signal and Ki-67 index. Moreover, elevated choline and choline/creatine ratio differentiated between sparsely and densely granulated GH-secreting PAs. MRS detected low hepatic lipid content in active acromegaly, which increased after disease control. The panel of metabolites of acromegaly deciphered by mass spectrometry (MS)-based techniques mainly included amino acids (especially branched-chain amino acids and taurine), glyceric acid, and lipids. The most altered pathways in acromegaly were the metabolism of glucose (particularly the downregulation of the pentose phosphate pathway), linoleic acid, sphingolipids, glycerophospholipids, arginine/proline, and taurine/hypotaurine. Matrix-assisted laser desorption/ionization coupled with MS imaging confirmed the functional nature of GH-secreting PAs and accurately discriminated PAs from healthy pituitary tissue.
Topics: Humans; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma; Magnetic Resonance Imaging; Metabolomics; Adenoma
PubMed: 37139720
DOI: 10.1177/10815589231169452 -
Critical Reviews in Microbiology Jul 2023The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often... (Review)
Review
The formation of bacterial biofilms in the human body and on medical devices is a serious human health concern. Infections related to bacterial biofilms are often chronic and difficult to treat. Detailed information on biofilm formation and composition over time is essential for a fundamental understanding of the underlying mechanisms of biofilm formation and its response to anti-biofilm therapy. However, information on the chemical composition, structural components of biofilms, and molecular interactions regarding metabolism- and communication pathways within the biofilm, such as uptake of administered drugs or inter-bacteria communication, remains elusive. Imaging these molecules and their distribution in the biofilm increases insight into biofilm development, growth, and response to environmental factors or drugs. This systematic review provides an overview of molecular imaging techniques used for bacterial biofilm imaging. The techniques included mass spectrometry-based techniques, fluorescence-labelling techniques, spectroscopic techniques, nuclear magnetic resonance spectroscopy (NMR), micro-computed tomography (µCT), and several multimodal approaches. Many molecules were imaged, such as proteins, lipids, metabolites, and quorum-sensing (QS) molecules, which are crucial in intercellular communication pathways. Advantages and disadvantages of each technique, including multimodal approaches, to study molecular processes in bacterial biofilms are discussed, and recommendations on which technique best suits specific research aims are provided.
PubMed: 37452571
DOI: 10.1080/1040841X.2023.2223704 -
Malaria Journal Sep 2023Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Global interest in malaria elimination has prompted research on active test and treat (TaT) strategies.
METHODS
A systematic review and meta-analysis were conducted to assess the effectiveness of TaT strategies to reduce malaria transmission.
RESULTS
A total of 72 empirical research and 24 modelling studies were identified, mainly focused on proactive mass TaT (MTaT) and reactive case detection (RACD) in higher and lower transmission settings, respectively. Ten intervention studies compared MTaT to no MTaT and the evidence for impact on malaria incidence was weak. No intervention studies compared RACD to no RACD. Compared to passive case detection (PCD) alone, PCD + RACD using standard diagnostics increased infection detection 52.7% and 11.3% in low and very low transmission settings, respectively. Using molecular methods increased this detection of infections by 1.4- and 1.1-fold, respectively.
CONCLUSION
Results suggest MTaT is not effective for reducing transmission. By increasing case detection, surveillance data provided by RACD may indirectly reduce transmission by informing coordinated responses of intervention targeting.
Topics: Humans; Malaria
PubMed: 37661286
DOI: 10.1186/s12936-023-04670-8