ABSTRACT
BACKGROUND: Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.
METHODS: This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10<20<1·32·67; NFS: <-1·4550·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.
FINDINGS: Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001
INTERPRETATION: Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases.
FUNDING: Innovative Medicines Initiative 2.
PMID:37290471 | DOI:10.1016/S2468-1253(23)00141-3
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PubMed articles on: Cardio-Oncology
The Efficacy of Multi-Leaf Collimator in the Reduction of Cardiac and Coronary Artery Dose in Left-Sided Breast Cancer Radiotherapy
Adv Biomed Res. 2023 Apr 25;12:89. doi: 10.4103/abr.abr_342_21. eCollection 2023.
ABSTRACT
BACKGROUND: Multi-leaf collimator (MLC) is one of the efficient and cost-effective methods for protecting sensitive tissues around the target. This study aimed to evaluate the protective effect of MLC on the protection of sensitive organs in patients with left breast cancer.
MATERIALS AND METHODS: This study was performed on computed tomography (CT) scans of 45 patients with left breast cancer. Two treatment plans were completed for each patient. Only the heart and left lung were considered organs at risk in the first treatment plan, and in the second treatment plan, the left anterior descending artery (LAD) was also considered the organ at risk. It was covered as much as possible by the MLC. Dosimetric results of tumor and organ at risk (OARs) were extracted from the dose-volume histogram and compared.
RESULTS: The results showed that more LAD coverage by MLC leads to a significant reduction in the mean dose of OARs (P-value <0.05).5 (volume received the dose of 5 Gy) and V20 for the lung, V10, V25, and V30 for LAD, and V5, V20, V25, and V30 for the heart also decreased significantly (P-value
CONCLUSIONS: In general, better protection of LAD, heart, and lungs can be achieved by maximal shielding organs at risk by MLC in radiation therapy for patients with left breast cancer.
PMID:37288034 | PMC:PMC10241641 | DOI:10.4103/abr.abr_342_21
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PubMed articles on: Cardio-Oncology
Feasibility of Aerobic Exercise Training to Mitigate Cardiotoxicity of Breast Cancer Therapy: A Systematic Review and Meta-Analysis
Clin Breast Cancer. 2023 May 3:S1526-8209(23)00094-0. doi: 10.1016/j.clbc.2023.04.010. Online ahead of print.
ABSTRACT
BACKGROUND: Current anticancer treatments for breast cancer (BC) may cause cardiotoxicity. This study aimed to investigate the effectiveness of aerobic exercise in mitigating cardiotoxicity caused by BC therapy.
MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, and the Physiotherapy Evidence Database were searched until February 7, 2023. Clinical trials investigating the effectiveness of exercise training, including aerobic exercise, in BC patients receiving treatments that could cause cardiotoxicity were eligible. Outcome measures included cardiorespiratory fitness (CRF) (peak oxygen consumption, VO2peak), left ventricular ejection fraction, and peak oxygen pulse. Intergroup differences were determined by standard mean differences (SMD) and 95% confidence intervals (CIs). Trial sequential analysis (TSA) was utilized to ensure whether the current evidence was conclusive.
RESULTS: Sixteen trials involving 876 participants were included. Aerobic exercise significantly improved CRF measured by VO2peak in mL/kg/min (SMD 1.79, 95% CI 0.99-2.59) when compared to usual care. This result was confirmed through TSA. Subgroup analyses revealed that aerobic exercise given during BC therapy significantly improved VO2peak (SMD 1.84, 95% CI 0.74-2.94). Exercise prescriptions at a frequency of up to 3 times per week, an intensity of moderate to vigorous, and a >30-minute session length also improved VO2peak.
CONCLUSION: Aerobic exercise is effective in improving CRF when compared to usual care. Exercise performed up to 3 times per week, at a moderate-to-vigorous intensity, and having a session length >30 minutes is considered effective. Future high-quality research is needed to determine the effectiveness of exercise intervention in preventing cardiotoxicity caused by BC therapy.
PMID:37286435 | DOI:10.1016/j.clbc.2023.04.010
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PubMed articles on: Cardio-Oncology
Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design
J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.
ABSTRACT
AIMS: Anthracyclines are the chemotherapeutic agents most frequently associated with cardiotoxicity, while remaining widely used. Different neurohormonal blockers have been tested as a primary prevention strategy to prevent or attenuate the onset of cardiotoxicity, with mixed results. However, prior studies were often limited by a nonblinded design and an assessment of cardiac function based only on echocardiographic imaging. Moreover, on the basis of an improved mechanistic understanding of anthracycline cardiotoxicity mechanisms, new therapeutic strategies have been proposed. Among cardioprotective drugs, nebivolol might be able to prevent the cardiotoxic effects of anthracyclines, through its protective properties towards the myocardium, endothelium, and cardiac mitochondria. This study aims to evaluate the cardioprotective effects of the beta blocker nebivolol in a prospective, placebo-controlled, superiority randomized trial in patients with breast cancer or diffuse large B cell lymphoma (DLBCL) who have a normal cardiac function and will receive anthracyclines as part of their first-line chemotherapy programme.
METHODS: The CONTROL trial is a randomized, placebo-controlled, double-blinded, superiority trial. Patients with breast cancer or a DLBCL, with a normal cardiac function as assessed by echocardiography, scheduled for treatment with anthracyclines as part of their first-line chemotherapy programme will be randomized 1 : 1 to nebivolol 5 mg once daily (o.d.) or placebo. Patients will be examined with cardiological assessment, echocardiography and cardiac biomarkers at baseline, 1 month, 6 months and 12 months. A cardiac magnetic resonance (CMR) assessment will be performed at baseline and at 12 months. The primary end point is defined as left ventricular ejection fraction reduction assessed by CMR at 12 months of follow-up.
CONCLUSION: The CONTROL trial is designed to provide evidence to assess the cardioprotective role of nebivolol in patients undergoing chemotherapy with anthracyclines.
CLINICAL TRIAL REGISTRATION: The study is registered in the EudraCT registry (number: 2017-004618-24) and in the ClinicalTrials.gov registry (identifier: NCT05728632).
PMID:37285278 | DOI:10.2459/JCM.0000000000001491
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PubMed articles on: Cardio-Oncology
Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity
Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun 7. doi: 10.1007/s00210-023-02566-7. Online ahead of print.
ABSTRACT
Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.
PMID:37284897 | DOI:10.1007/s00210-023-02566-7
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PubMed articles on: Cancer & VTE/PE
COVID-19 related acute necrotizing encephalopathy presenting in the early postoperative period
Arch Clin Cases. 2023 Jun 7;10(2):78-85. doi: 10.22551/2023.39.1002.10246. eCollection 2023.
ABSTRACT
Besides respiratory and gastrointestinal symptoms, SARS-CoV-2 also has potential neurotropic effects. Acute hemorrhagic necrotizing encephalopathy is a rare complication of Covid-19. This article presents a case of an 81-year-old female, fully vaccinated, who underwent laparoscopic transhiatal esophagectomy due to gastroesophageal junction cancer. In the early postoperative period, the patient developed persistent fever accompanied by acute quadriplegia, impaired consciousness, and no signs of respiratory distress. Imaging with Computed Tomography and Magnetic Resonance revealed multiple bilateral lesions both in gray and white matter, as well as pulmonary embolism. Covid-19 infection was added to the differential diagnosis three weeks later, after other possible causes were excluded. The molecular test obtained at that time for coronavirus was negative. However, the high clinical suspicion index led to Covid-19 antibody testing (IgG and IgA), which confirmed the diagnosis. The patient was treated with corticosteroids with noticeable clinical improvement. She was discharged to a rehabilitation center. Six months later, the patient was in good general condition, although a neurological deficit was still present. This case indicates the significance of a high clinical suspicion index, based on a combination of clinical manifestations and neuroimaging, and the confirmation of the diagnosis with molecular and antibody testing. Constant awareness of a possible Covid-19 infection among hospitalized patients is mandatory.
PMID:37293685 | PMC:PMC10246599 | DOI:10.22551/2023.39.1002.10246
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PubMed articles on: Cancer & VTE/PE
Incidence and risk factors for venous thromboembolism in patients with ovarian cancer during neoadjuvant chemotherapy: a meta-analysis
Am J Cancer Res. 2023 May 15;13(5):2126-2134. eCollection 2023.
ABSTRACT
In recent years, there has been increasing recognition of the relationship between neoadjuvant chemotherapy (NACT) in ovarian cancer and the incidence rate of venous thromboembolism (VTE). Some studies have suggested that NACT may be associated with a high risk of VTE in patients with ovarian cancer. To investigate this, we conducted a systematic review and meta-analysis of the incidence of VTE during NACT and its associated risk factors. We searched PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN) from their inception to September 15, 2022. We calculated the incidence of VTE as the event rate (%) and used logistic regression analysis to investigate pooled VTE rates. Risk factors for VTE were presented as odds ratios (ORs), and pooled ORs was estimated using the inverse variance method. We reported pooled effect estimates with 95% confidence intervals (CIs). Our review included 7 cohort studies with 1244 participants. Meta-analysis of these studies revealed a pooled VTE rate of 13% during NACT (1224 participants; 95% CI, 9%-17%), with body mass index identified as a risk factor for VTE during NACT in 3 of the included studies (633 participants; OR, 1.76; 95% CI, 1.13-2.76).
PMID:37293158 | PMC:PMC10244120
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PubMed articles on: Cancer & VTE/PE
Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomisation analysis
medRxiv. 2023 May 18:2023.05.16.23289792. doi: 10.1101/2023.05.16.23289792. Preprint.
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