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Frontiers in Oncology 2024This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across...
AIM
This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites.
METHODS
We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023.
RESULTS
In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs.
CONCLUSION
This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs.
SYSTEMATIC REVIEW REGISTRATION
INPLASY platform, identifier INPLASY202380119.
PubMed: 38826783
DOI: 10.3389/fonc.2024.1391724 -
Targeted Oncology Jun 2024Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer....
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) remain the frontline standard of care for patients with EGFR-mutant non-small cell lung cancer. An updated toxicity profile of EGFR-TKIs proves valuable in guiding clinical decision making.
OBJECTIVE
This study comprehensively assessed the risk of EGFR-TKI-related adverse events (AEs) involving different systems/organs.
METHODS
We systematically searched PubMed, Embase, Web of Science, and Cochrane library for phase III randomized controlled trials comparing EGFR-TKI monotherapy with placebo or chemotherapy in patients with non-small cell lung cancer. The odds ratio (OR) of all-grade and high-grade adverse events (AEs) including dermatologic, gastrointestinal, hematologic, hepatic, and respiratory events was pooled for a meta-analysis. Subgroup analyses based on the control arm (placebo or chemotherapy) and individual EGFR-TKIs (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) were conducted.
RESULTS
Thirty-four randomized controlled trials comprising 15,887 patients were included. The pooled OR showed EGFR-TKIs were associated with a significantly increased risk of all-grade dermatologic AEs including paronychia, pruritus, rash, skin exfoliation, and skin fissures, gastrointestinal AEs including abdominal pain, diarrhea, dyspepsia, mouth ulceration, and stomatitis, hepatic AEs including elevated alanine aminotransferase and aspartate aminotransferase, and respiratory AEs including epistaxis, interstitial lung disease and rhinorrhea. Furthermore, a significantly increased risk of high-grade rash (OR 7.83, 95% confidence interval [CI] 5.11, 12.00), diarrhea (OR 2.10, 95% CI 1.44, 3.05), elevated alanine aminotransferase (OR 3.93, 95% CI 1.71, 9.03), elevated aspartate aminotransferase (OR 3.22, 95% CI 1.05, 9.92) and interstitial lung disease (OR 2.35, 95% CI 1.38, 4.01) was observed in patients receiving EGFR-TKIs. When stratified by individual EGFR-TKIs, gefitinib showed a significant association with all-grade and high-grade hepatotoxicity and interstitial lung disease.
CONCLUSIONS
Epidermal growth factor receptor tyrosine kinase inhibitors were associated with a significantly increased risk of various types of AEs. Clinicians should be vigilant about the risks of these EGFR-TKI-related AEs, particularly for severe hepatotoxicity and interstitial lung disease, to facilitate early detection and proper management.
PubMed: 38824269
DOI: 10.1007/s11523-024-01073-w -
Reviews on Recent Clinical Trials May 2024β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
BACKGROUND
β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties.
OBJECTIVE
This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on β-thalassemia outcomes in children and adolescents.
METHODS
A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety.
RESULTS
By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects.
CONCLUSION
Silymarin indicates promising effects on various aspects of children and adolescents with β-thalassemia and has no serious side effects on the investigated dosage.
PubMed: 38818907
DOI: 10.2174/0115748871305325240511122602 -
Expert Opinion on Pharmacotherapy May 2024Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is estimated to affect upto 70-80% of people with type 2 diabetes mellitus (T2DM). Although several... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is estimated to affect upto 70-80% of people with type 2 diabetes mellitus (T2DM). Although several anti-hyperglycemic drugs have been shown to be effective in such patients, there remains an unmet need for newer drugs. The objective of this meta-analysis was to analyze the effect of ipragliflozin on aspartate aminotransferase (AST), alanine transaminase (ALT), and gamma-glutamyl transpeptidase (GGT) levels in patients with T2DM.
METHODS
A literature search on electronic databases was conducted to identify potential randomized clinical trials (RCT) as per predetermined study selection criteria. Mean difference (MD) was calculated using Cochrane review manager.
RESULTS
Twelve studies were included in the meta-analysis, including 1349 subjects. Compared to the control group, ipragliflozin as a monotherapy showed a significant reduction in levels of ALT at week 12 ( = 0.02) and at week 24 ( = 0.007), GGT at week 12 ( < 0.00001). Ipragliflozin as an add-on therapy showed significant reduction in levels of AST at week 24 ( < 0.00001), ALT at week 12 ( = 0.002), ALT at week 24 ( < 0.00001), and GGT at week 24 ( < 0.00001).
CONCLUSION
Findings suggest the beneficial effects of ipragliflozin on liver enzymes. Further large-scale RCTs are required to confirm ipragliflozin's role for liver-related conditions in T2DM.
Topics: Humans; Alanine Transaminase; Aspartate Aminotransferases; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Fatty Liver; gamma-Glutamyltransferase; Glucosides; Hypoglycemic Agents; Liver; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors; Thiophenes
PubMed: 38804904
DOI: 10.1080/14656566.2024.2360078 -
PloS One 2024This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice.
METHODS
A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool.
RESULTS
A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant.
CONCLUSION
The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.
Topics: Animals; Liver Cirrhosis; Curcumin; Mice; Rats; Disease Models, Animal; Oxidative Stress; Liver
PubMed: 38781262
DOI: 10.1371/journal.pone.0304176 -
Clinical epidemiology and outcomes of emergency department-acute kidney injury: A systematic review.Heliyon May 2024Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI)...
BACKGROUND
Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI) is poorly characterised, poorly understood with no systematic review, often under-recognized and under-managed.
OBJECTIVE
To review the incidence, risk factors, and outcomes of ED-AKI, and risk factors of post-ED-AKI mortality globally.
METHODS
We included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 h of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to August 14, 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a Forest plot to present pooled ED-AKI incidence rates and I statistics. Other parameters were summarized narratively.
RESULTS
Using 24 h from ED admission as the definition for ED-AKI we identified six articles from 2005 to 2018 in high-income settings and one article with a 48-h timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. Crude, all-cause 24-h mortality rate was 4.56 % and the one-year mortality rate was 35.04 %. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates.
CONCLUSION
The review reveals a paucity of relevant literature which calls for further research, increased vigilance, red flag identification, and standardized management protocols for ED-AKI.
PubMed: 38756601
DOI: 10.1016/j.heliyon.2024.e30580 -
Journal of Molecular Medicine (Berlin,... Jul 2024Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it... (Review)
Review
Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Biomarkers; Prognosis
PubMed: 38753041
DOI: 10.1007/s00109-024-02448-2 -
Cureus Apr 2024In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a... (Review)
Review
In 2021 and 2022, there were noted to be clusters of pediatric acute hepatitis of unknown origin (AHUO) occurring across the globe. While there was not necessarily a global increase in cases, understanding the pattern of liver injury in AHUO is crucial to properly identify cases of this unexplained phenomenon, especially since it occurred simultaneously with a global resurgence of COVID-19. The objective of this study was to contrast the patterns in liver-relevant biochemical data from COVID-19 patients and AHUO. Studies reporting liver chemistries for cases of AHUO and COVID-19 were identified by a systematic review and search of the literature. For each case, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, direct bilirubin, and international normalized ratio (INR) levels were extracted as available. These were normalized to multiples of the upper limit of normal by patient age. There were statistically significant greater elevations of ALT and AST in patients with AHUO than in those with COVID-19. Only a subset of patients with COVID-19 had an AST or ALT greater than the normal range. INR elevation could be substantial for both conditions but was also statistically higher in the AHUO group. Liver chemistry changes were not statistically correlated with age. The pattern of liver chemistry changes between AHUO and COVID-19 have some distinctions, which suggests that AHUO is not a phenomenon driven primarily by SARS-CoV-2 infection alone. Differentiating AHUO and COVID-19 would be challenging based on patterns of liver chemistry changes alone.
PubMed: 38752102
DOI: 10.7759/cureus.58307 -
Canadian Liver Journal May 2024Curcumin is an anti-inflammatory that is proposed to have a positive impact on patients with non-alcoholic fatty liver disease (NAFLD). We aim to assess the effects of...
BACKGROUND
Curcumin is an anti-inflammatory that is proposed to have a positive impact on patients with non-alcoholic fatty liver disease (NAFLD). We aim to assess the effects of curcumin in patients with NAFLD.
METHODS
Clinical trials from PubMed, Scopus, the Web of Science, and Cochrane CENTRAL with variables alanine transferase, aspartate transaminase, alkaline phosphatase, glycated hemoglobin (HBA1c), BMI, waist circumference, total cholesterol, total glycerides, high-density lipoproteins, and low-density lipoproteins were included. Homogeneous and heterogeneous were analyzed under a fixed-effects model and the random-effects model, respectively.
RESULTS
Fourteen clinical trials found that curcumin has no statistically significant effect on alanine transferase (MD = -2.20 [-6.03, 1.63], = 0.26], aspartate transaminase (MD = 1.37 [-4.56, 1.81], = 0.4), alkaline phosphatase (MD = 3.06 [-15.85, 9.73], = 0.64), glycated hemoglobin (HBA1c), (MD = -0.06 [-0.13, 0.02], = 0.16], and BMI (MD = 0.04 [-0.38, 0.46], = 0.86). Curcumin reduced the waist circumference (MD = -4.87 [-8.50, -1.25], = 0.008). Lipid profile parameters were not significant, except the total glycerides (MD = -13.22 [-24.19, -2.24], = 0.02).
CONCLUSIONS
Curcumin significantly reduces total glycerides and waist circumference in NAFLD.
PubMed: 38746865
DOI: 10.3138/canlivj-2023-0022 -
Photodiagnosis and Photodynamic Therapy Jun 2024Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of... (Review)
Review
BACKGROUND
Protoporphyrin IX (PPIX) is the final precursor of heme, forming heme when iron is inserted. Individuals with erythropoietic protoporphyrias (EPP) have accumulation of PPIX, causing photosensitivity and increased liver disease risk. Many also have iron deficiency and anemia. We investigated outcomes of oral iron supplements in individuals with EPP.
METHODS
A systematic review identified literature on oral iron supplements in EPP patients. Subsequently, we administered iron supplements to EPP patients with iron deficiency. The primary outcome was impact on PPIX level. Secondary outcomes were adverse events and relative differences in hemoglobin and iron parameters.
RESULTS
The systematic review found 13 case reports and one uncontrolled clinical trial with uncertain results. From our department 10 patients with EPP and iron deficiency took daily dosages of 330 mg of ferrous fumarate for two months. Five of our patients had anemia at baseline. After 2 months of supplementation seven patients had increased PPIX level compared to baseline, two had decrease, one remained unchanged. The administration of iron led to a rise in ferritin, and in four of the anemic patients also to an improvement in blood hemoglobin. A small transiently elevation in plasma alanine transaminase concentration was observed during supplementation.
CONCLUSIONS
Overall, iron supplementation in EPP patients replenished iron stores and elevated erythrocyte PPIX and plasma alanine transaminase. For anemic patients, there was some degree of normalization of the hemoglobin level. If iron therapy is needed for EPP patients, monitoring of photosensitivity, PPIX, hemoglobin, and plasma liver enzymes is advisable.
Topics: Humans; Protoporphyria, Erythropoietic; Protoporphyrins; Dietary Supplements; Male; Female; Adult; Iron; Anemia, Iron-Deficiency; Middle Aged; Treatment Outcome
PubMed: 38734198
DOI: 10.1016/j.pdpdt.2024.104211